Al Fin Longevity

Important New Insights into Alzheimer's Disease from Cultured Adult Induced Stem Cells from Alzheimer's Patients

2012-01-26T09:08:00.000-08:00

When you take skin cells from an Alzheimer's patient, and turn them into neurons in culture, you can study these "Alzheimer's neurons" in detail in the lab. This ability to work with cultured human Alzheimer neurons from induced stem cells, on a day to day basis, will give scientists an intimate familiarity with the genetic and biochemical differences which lead to the pathological changes in the disease. And none too soon, because as western societies grow older, Alzheimer's is threatening to bankrupt their social medicine services.

The feat, published in the January 25 online edition of the journal Nature, represents a new and much-needed method for studying the causes of AD, a progressive dementia that afflicts approximately 5.4 million Americans. More importantly, the living cells provide an unprecedented tool for developing and testing drugs to treat the disorder.

“We’re dealing with the human brain. You can’t just do a biopsy on living patients,” said Goldstein. “Instead, researchers have had to work around, mimicking some aspects of the disease in non-neuronal human cells or using limited animal models. Neither approach is really satisfactory.”

Goldstein and colleagues extracted primary fibroblasts from skin tissues taken from two patients with familial AD (a rare, early-onset form of the disease associated with a genetic predisposition), two patients with sporadic AD (the common form whose cause is not known) and two persons with no known neurological problems. They reprogrammed the fibroblasts into induced pluripotent stem cells (iPSCs) that then differentiated into working neurons.

The iPSC-derived neurons from the Alzheimer’s patients exhibited normal electrophysiological activity, formed functional synaptic contacts and, critically, displayed tell-tale indicators of AD. Specifically, they possessed higher-than-normal levels of proteins associated with the disorder.

With the in vitro Alzheimer’s neurons, scientists can more deeply investigate how AD begins and chart the biochemical processes that eventually destroy brain cells associated with elemental cognitive functions like memory. Currently, AD research depends heavily upon studies of post-mortem tissues, long after the damage has been done.

“The differences between a healthy neuron and an Alzheimer’s neuron are subtle,” said Goldstein. “It basically comes down to low-level mischief accumulating over a very long time, with catastrophic results.”

The researchers have already produced some surprising findings. “In this work, we show that one of the early changes in Alzheimer’s neurons thought to be an initiating event in the course of the disease turns out not to be that significant,” Goldstein said, adding that they discovered a different early event plays a bigger role.

The scientists also found that neurons derived from one of the two patients with sporadic AD exhibited biochemical changes possibly linked to the disease. The discovery suggests that there may be sub-categories of the disorder and that, in the future, potential therapies might be targeted to specific groups of AD patients.

Though just a beginning, Goldstein emphasized the iPSC-derived Alzheimer’s neurons present a huge opportunity in a desperate fight. _UCSD

This research is geared specifically toward Alzheimer's disease research, since Alzheimer's patients are the donours of the original cells being used. But the same approach can be used to culture a wide range of induced cell types, from patients with a wide range of disease types. In other words, this is just the beginning of a beautiful approach to bringing the full dynamics of human diseases into the laboratory for thorough study.

There is no way of predicting what possibilities may arise from this research over the long run.

3 Dimensional Bio-Cell Printing: Future Tissue & Organ Replacements

2012-01-16T19:55:00.000-08:00

An optimized 3D inkjet printing process is demonstrated for structuring alginate into a tissue-like microvasculature capable of supporting physiological flow rates. Optimizing the reaction at the single-droplet level enables wet hydrogel droplets to be stacked, thus overcoming their natural tendancy to spread and coalesce. Live cells can be patterned using this process and it can be extended to a range of other hydrogels. _Advanced Materials

The dream is to be able to rapidly grow replacement tissues and organs, to allow for easy autologous replacement for a wide range of clinical reasons and circumstances -- including life extension regenerative treatments.

...Thus, it would take just under 2 hours to print a 1 cm thick tissue precursor graft and just over 5 h 30 to print a 3 cm thick kidney precursor. _Advanced Materials PDF

Swiss scientists are using a special inkjet printer to assemble three dimensional living constructs that resemble living tissues. They are still in the early stages of the research, but are achieving some interesting results.
They are working on a technique that should eventually allow them to “print” living constructs resembling human tissues in which cells can develop and interact in a coordinated and physiological manner. Their research results have recently been published in the scientific journal Advanced Materials.

“We have not yet created tissue, strictly speaking,” explains Professor Jürgen Brügger, head of EPFL’s Microsystems 1 Laboratory. “At this stage, we have essentially studied a way in which to structure biological materials in three dimensions; this research will improve cell culture and then will eventually be used as a base for creating tissues.”

...To make up a coherent whole, the cells need an environment that provides the right kinds of signals that induce very specific behavior in each of the cells – proliferation, migration, differentiation or death. In natural tissues, these signals come from molecules that make up a complex extracellular matrix (ECM). By studying the connections and communications taking place between cells and between cells and ECM molecules, the scientists were able to reconstruct this matrix and thus create a new kind of biological ink.

On a technical level, the researchers from EPFL’s two Microsystems Laboratories – under the leadership of professors Jürgen Brugger and Philippe Renaud – focused on developing a gel that could be used as a base from which the tissue could be constructed, as well as a strategy for printing droplets.

...Even though it will still be quite some time before tissue can be constructed, this technology could lead to very promising applications on the medium term. “ An exiting avenue would be to develop 3D constructs that function like human tissues and could be used as models for testing new drugs,” says Lutolf. “This is not only very interesting in a biological sense, but could also reduce the need for animal testing.” _Physorg

Learning to create life-like 3 dimensional cell cultures for research, and learning to create 3-D lab-made living tissues for replacement, are not quite the same things. But the two lines of research are likely to borrow from and contribute to each other, extensively.

This research used fibroblasts. Future research is likely to use a variety of stem cells and other precursor cells for various cell types.

Non-fluorescent NIH 3T3 fibroblasts were used in this printing as to be compatible with the fluorescent Live-Dead assay. The cells were suspended in culture medium supplemented with 0.8% wt. non-fluorescent alginate at a concentration of 1x10 6 mL -1 . Cells were inkjet printed onto 2% wt. gelatin substrates prepared with 0.9% wt. NaCl and 10 mM CaCl2, prepared in a 96-well plate. All cells were incubated for 4h before Live-Dead staining. _Advanced Materials

Living More of Your Time: Enjoying and Mastering Alcohol

2012-01-06T08:39:00.000-08:00

A person may "live" between 70 and 80 years, but only truly experience a relatively few years of life. After subtracting the time a person spends either sleeping, intoxicated, in childhood / adolescence, or in declining senescence, very few optimally productive years of time may be left.

An herbal chemical has been discovered which may well allow us to reduce our impairment from alcohol intoxication, giving us more time to appreciate, enjoy, and profit from our lives.
Led by Jing Liang from the University of California, researchers began looking at different herbs that have natural anti-alcohol properties. They found descriptions of anti-alcohol properties of the Asian tree Hovenia dulcis that dated back to 659. These descriptions listed it as a prime hangover remedy.

The main ingredient in Hovenia dulcis is known as dihydromyricetin, or DHM. The team of researchers used rats to test out the effects. Rats react similar to humans when it comes to the effects of alcohol so they are a perfect candidate.

The rats were given the human equivalent of 15-20 beers in a time frame of under two hours. As expected, the rats passed out drunk and lost the ability to flip themselves over when placed on their back. Within an hour, the effects of the alcohol started to wear off and they were able to again control their bodies.

When the rats were given the same alcohol with a shot of the DHM, they still eventually lost the ability to flip over but it took a longer time period and they were able to recover from the effects in about 15 minutes.

The effects of the DHM went beyond that though. Two days after the alcohol consumption, the rats that were given the DHM showed less signs of hangover symptoms such as anxiety and seizures.

The other noted result was the reduction in addiction. When the rats were allowed to drink freely, they would gradually start consuming more. However, those rats that had received the DHM did not increase consumption. _MedicalXpress
The promise of this herb goes far beyond a treatment for alcohol addiction. It promises to give us back a great deal of the time that we voluntarily sacrifice to alcohol -- and the aftereffects of alcoholic indulgence.

How many bad choices do people make under the influence of alcohol, which lead to further destruction of our time and our lives -- as well as the premature ending of many innocent lives?

Earlier we looked at ways that we may safely reduce our sleeping time -- thus adding years to our lives. If we can also reduce much of the time wasted by intoxicants, we may well have added significantly more profitable time to our lives.

Life extension is about more than simply "living" more years. It is also about truly living the time that you are alive.

http://www.jneurosci.org/content/32/1/390.abstract: Article abstract link

Young Stem Cells In Old Mice Increased Lifespan

2012-01-03T09:45:00.000-08:00

A special breed of mice lived up to three times longer than normal after University of Pittsburgh researchers injected them with stem cells from younger, healthy mice, according to a study being published today in the journal Nature Communications.

Working with mice that are bred to die prematurely, Pitt researchers led by Johnny Huard and Laura Niedernhofer dramatically increased the animals' lifespans by injecting them in the abdomen with young animals' muscle stem cells. _Post-Gazette

Keep in mind that this research was done in a special breed of mouse that is programmed to have a shorter lifespan. Additional research will be required to determine if normal ageing mice can benefit from similar treatment.
"We wanted to see if we could rescue these rapidly aging animals, so we injected stem/progenitor cells from young, healthy mice into the abdomens of 17-day-old progeria mice," Dr. Huard said. "Typically the progeria mice die at around 21 to 28 days of age, but the treated animals lived far longer – some even lived beyond 66 days. They also were in better general health."

As the progeria mice age, they lose muscle mass in their hind limbs, hunch over, tremble, and move slowly and awkwardly. Affected mice that got a shot of stem cells just before showing the first signs of aging were more like normal mice, and they grew almost as large. Closer examination showed new blood vessel growth in the brain and muscle, even though the stem/progenitor cells weren't detected in those tissues.

In fact, the cells didn't migrate to any particular tissue after injection into the abdomen.
"This leads us to think that healthy cells secrete factors to create an environment that help correct the dysfunction present in the native stem cell population and aged tissue," Dr. Niedernhofer said. "In a culture dish experiment, we put young stem cells close to, but not touching, progeria stem cells, and the unhealthy cells functionally improved." _MedXpress
Stem cells can conceivably be used for many purposes, in the treatment of ageing. In the case of the above research, the stem cells apparently secreted some type of hormonal growth factor which was lacking in the progeria mice.

But in future, more sophisticated uses of stem cells to treat ageing, stem cells will be used for tissue replacement, organ regeneration and replacement, humoral factor replacement, and probably other uses not yet discovered.

A Lesson in Basic Gene Expression

2011-12-24T11:50:00.000-08:00

Directions for making proteins are encoded in the DNA sequences of genes, which reside on chromosomes in the nucleus of each cell. But for proteins to be made, a gene’s DNA code must be copied, or transcribed, onto mRNA molecules, which migrate from the nucleus and into the cytoplasm where the cell’s protein-making machinery is located. For as long as it exists, an mRNA molecule can act as a template for making copies of a protein. So scientists have long suspected that cells must have ways for degrading mRNAs when, for example, a protein starts accumulating to harmful levels. “The cell somehow decides to destroy its mRNA on cue, but nobody knew how this happens,” said Dr. Singer. _EinsteinNews

Gene Expression Image
Understanding gene expression is one of the keys to the discovery of how to live much longer and healthier lives. The basic outline of gene expression has been known for several decades, but the details of control and timing of the complex networks of gene expression are just being exposed.

Scientists at Albert Einstein College of Medicine recently made a basic discovery in the control of messenger RNA lifespan, which may help to unlock one of the important doors to understanding.
When genes are transcribed, a part of the gene called the promoter region has the job of switching on the gene so that DNA will be copied into mRNA. The Einstein scientists found that the promoter regions of the SWI5 and CLB2 genes do something else as well: they recruit a protein called Dbf2p, which jumps onto mRNA molecules as they’re being synthesized.

These mRNAs—transcribed from the SWI5 and CLB2 genes and bearing the Dbf2p protein—make their journey from the nucleus into the cytoplasm. Here a protein called Dbf20p joins Dbf2p aboard the mRNA molecules—and the two proteins together call for the molecules’ precipitous decay.

“Our findings indicate that genes making proteins whose levels must be carefully controlled contain promoter regions that sentence their mRNA molecules to death even as the mRNA is being born,” said Dr. Singer. “The promoter regions do that by ‘marking’ the newly made mRNA with the protein Dbf2p—the common factor between mRNA synthesis and its ultimate decay. Dbf2p stays attached to the mRNA from its birth and then, responding to a signal indicating that no more protein should be made, orders mRNA’s destruction.” _EinsteinNews

You see, as long as the messenger RNA stays around in the cytoplasm, it will keep binding to ribosomes, and continue to produce its protein. This is not what the cell wants, in general, since the relative quantities of different proteins are maintained in a healthy balance.

The application of this discovery to life extension is not immediately apparent to the casual reader. And yet as we come to understand the build-up of imbalances within cells which accompany the ageing process, we are likely to find multiple ways in which this particular system can go wrong, and contribute to degenerative changes.

The better we understand this complex dance of molecules, the better will be our solutions to the problems that occur when the complex system begins to break down. Eventually, we will probably want to re-design some of these sub-systems in ways to make them more robust.

PDF of actual study, published in Cell

Salk Researchers Take a Stab at New Approach to Alzheimer's Tx

2011-12-19T16:34:00.000-08:00

At present, there are few drugs that improve the memory deficits associated with normal aging and none that prevent cognitive decline in chronic neurodegenerative conditions such as Alzheimer's disease (AD). Except for the rare cases of familial AD, the cause of AD is not known, but the disease is highly correlated with aging, a process involving a wide variety of physiological changes. Therefore, it is likely that the cells in the aging brain are compromised not from a single cause but from the convergence of multiple insults. However, the currently most widely used approach to drug discovery is to identify a single molecular target and then make a drug that alters this target [1]. Unfortunately, drugs for AD that were developed through this approach have all failed in clinical trials, perhaps because one target is not sufficient or because the targets are also critical for normal brain function so that their inactivation results in toxicity. Therefore, a different approach to drug discovery for AD is needed [2], [3]. _PLoS

Currently, the major drug discovery paradigm for neurodegenerative diseases is based upon high affinity ligands for single disease-specific targets. For Alzheimer's disease (AD), the focus is the amyloid beta peptide (Aß) that mediates familial Alzheimer's disease pathology. However, given that age is the greatest risk factor for AD, we explored an alternative drug discovery scheme that is based upon efficacy in multiple cell culture models of age-associated pathologies rather than exclusively amyloid metabolism. Using this approach, we identified an exceptionally potent, orally active, neurotrophic molecule that facilitates memory in normal rodents, and prevents the loss of synaptic proteins and cognitive decline in a transgenic AD mouse model. _PLoS

The "amyloid hypothesis" has not been a productive research pathway for finding cures for Alzheimer's -- at least not yet. Salk researchers chose to develop a new series of pharmacological agents based upon the neuroprotective action of the herb curcumin. Curcumin does not enter the brain in high enough concentrations to reverse the symptoms of Alzheimer's Disease, once the disease has progressed to the symptomatic stage. But the new Salk molecules, based upon curcumin's effect, are able to reverse some of the signs of neurodegeneration in aging animal brains.

If the new drug -- J147 -- proves to be effective, and is as safe as curcumin itself, it is likely to become the prototype for a new approach to treating neurodegeneration of aging in general, and Alzheimer's in particular.

H/T Gizmag

Monoclonal Antibody Prophylactic Injection for Alzheimer's Disease

2011-12-04T08:25:00.000-08:00

We are learning how to diagnose Alzheimer's disease before it has begun to manifest symptoms. Genomic studies tell us who is most likely to develop the disease, and new lab tests and scanning tools can identify the disease in its earliest stages, before it starts causing apparent problems. But it is not helpful to know that a person is doomed to suffer Alzheimer's unless you have a useful treatment or preventative. Now, such a prophylactic treatment for Alzheimer's is being studied in Britain: Gantenerumab, a monoclonal antibody against amyloid protein.
....gantenerumab, made by Roche, is designed to be given up to four years before the disease has been diagnosed. It is aimed at people with memory problems that have caused them concern but who are still able to go about their day-to-day lives.

It contains an antibody that homes in on amyloid, the toxic protein that clogs the brain in Alzheimer’s, and speeds up its clearance from the body. In small-scale early trials on men and women who already had Alzheimer’s, it cut the amount of amyloid in the brain by up to a third in just six months, the journal Archives of Neurology reports.

It is hoped that giving it earlier would be even more effective and the drug is now being tested on 360 people in 15 countries with mild memory problems that are expected to progress to dementia. To take part in the trial, people must be aged between 50 and 89 and have memory problems that are causing them concern.

A lumbar puncture will confirm that amyloid is building up in their system, although they have yet to be diagnosed with dementia. Those taking part in the Scarlet Road Study trial will be given gantenerumab every month for two years, or a dummy drug.

...Dr Perry, a consultant neurologist at London’s Charing Cross Hospital and at the Re:Cognition Health memory clinic, said: ‘We know that the amyloid is there for many years beforehand and it is thought that if you are going to reduce the amounts to have an effect, we have got to do that before people have significant damage.’

Barbara Sahakian, a professor at Cambridge University’s psychiatry department, said she was ‘thrilled’ by the launch of the trial. She said: ‘The implications are far-reaching.
‘On a personal level, being able to stay at work and maintain your family life and all your hobbies and interests would be just fabulous. ‘There are also great implications for relatives and for society. ‘Institutional care is extremely expensive and if we had effective treatments, we could use that money in a different way.’

Dr Marie Janson of Alzheimer’s Research UK said: ‘Although research into gantenerumab is still in its early phases, initial results have looked promising.’

To find out about joining the trial, visit www.scarletroadstudy.com _DailyMail_via_ImpactLab

Advanced societies around the world are ageing quickly, due to a reduction in birthrates plus lifespans that keep extending due to better food, sanitation, health habits, and health care. As more people reach old age, Alzheimer's disease will become more prevalent. As fewer people are born to support those who age, the disease will become a tremendous societal burden, unless effective treatments can extend a person's lucid lifespan along with the ability to be productive to a later age.

Brain Restoration in Alzheimer's Disease: Deep Brain Stimulates Reversal of Brain Shrinkage

2011-11-24T06:38:00.000-08:00

BRAIN shrinkage in people with Alzheimer's disease can be reversed in some cases - by jolting the degenerating tissue with electrical impulses. Moreover, doing so reduces the cognitive decline associated with the disease. _NS

NS
Alzheimer's disease is an increasingly common cause of total disability in the ageing population. One of the manifestations of Alzheimer's is a shrinking and shutting down of activity in multiple centres of the brain which are critical to memory function. Cells die and crucial brain tissue is lost, as part of the disease process. Now scientists at Toronto Western Hospital in Ontario, believe they may have found an effective approach -- for some.
The group inserted electrodes into the brains of six people who had been diagnosed with Alzheimer's at least a year earlier. They placed the electrodes next to the fornix - a bundle of neurons that carries signals to and from the hippocampus - and left them there, delivering tiny pulses of electricity 130 times per second.

Follow-up tests a year later showed that the reduced use of glucose by the temporal lobe and posterior cingulate had been reversed in all six people (Annals of Neurology, DOI: 10.1002/ana.22089).

The researchers have now begun to investigate the effects on the hippocampus. At the Society for Neuroscience annual meeting in Washington DC last week they announced that while they saw hippocampal shrinking in four of the volunteers, the region grew in the remaining two participants.

"Not only did the hippocampus not shrink, it got bigger - by 5 per cent in one person and 8 per cent in the other," says Lozano. It's an "amazing" result, he adds.

Tests showed that these two individuals appeared to have better than expected cognitive function, although the other four volunteers did not.

Though Lozano is not sure exactly how the treatment works, his team's recent work in mice suggests that the electrical stimulation might drive the birth of new neurons in the brain. Deep brain stimulation in mice also triggers the production of proteins that encourage neurons to form new connections _NS

This approach is worth pursuing further. It is too invasive to be used on a wide scale, but it is likely that there will be no shortage of volunteers for the procedure. What is learned from this research can be used to devise less invasive approaches which will be more appropriate for use in larger populations.

In the meantime, research into the use of pharmaceuticals, growth factors, and stem cell therapies for Alzheimer's will continue.

Proof of Concept for Rejuvenating Effect of Stem Cells: Pregnancy

2011-11-21T09:57:00.000-08:00

Stem cell research has been controversial for decades. But we are beginning to learn that stem cell rejuvenation therapy experiments have been taking place for as long as humans have walked the Earth.

In earlier articles, we explained how pregnancy can make a woman younger due to the transfer of certain molecules -- hormones, growth factors etc -- from the fetus to the mother. In another article we learned that pregnancy can help make women's brains work better. Now we learn that pregnant women's bodies can be regenerated via embryonic stem cell rejuvenation treatments from the fetus.

These findings come from research in mice done at Mount Sinai School of Medicine in New York:Mouse fetuses will give up stem cells to repair their mother's heart. The discovery could explain why half the women who develop heart weakness during or just after pregnancy recover spontaneously.

Hina Chaudhry of the Mount Sinai School of Medicine in New York City mated normal female mice with males genetically engineered to produce a green-fluorescing protein in all their body cells. Half the resulting fetuses also produced the protein, making it easy to spot any fetal tissue in the mother.

Chaudhry's team inflicted a heart attack on the pregnant mice and killed them two weeks later to take a look at their hearts. They found some fluorescent cells in the mothers' damaged heart tissue, where they had accelerated repair by changing into new heart cells, including beating cardiomyocytes and blood vessel cells.

Chaudhry says that the phenomenon is an evolutionary mechanism: the fetus promotes its own survival by protecting its mother's heart. Because the cells are easy to obtain from the placenta and unlikely to cause immunological reactions, they could provide a new and potentially limitless source of stem cells for repairing damaged hearts.

"The study is the first to show conclusively that fetal cells contained in the placenta assist in cardiac tissue repair," says Jakub Tolar, director of stem-cell therapies at the University of Minnesota in Minneapolis. _NewScientist
All the debate that has gone on over embryonic stem cell treatments, and we discover that it has been going on in mammals from the beginning.

Now it is a matter of learning how to maximise the positive effects of pregnancy, and to compensate for the potential negative effects.

Of course, in the long run, artificial wombs will relieve most women of the burden of gestation. But for those stylishly retro women who will wish to carry their own -- the advantages continue to build.

Above cross-posted from Al Fin, You Sexy Thing!

A One-Two Gene Knockout Makes Mice Stronger and Faster

2011-11-19T20:37:00.000-08:00

Swiss scientists have discovered that knocking out the nuclear receptor corepressor 1 (NCoR1) gene in the muscles of mice allow the animals to run farther, and faster. Knocking out the same gene in fat cells eliminated the problem of diabetes in the mice. And those are only two tissues, of the many types of tissues in a mouse's body. I wonder if knocking out the NCoR1 gene in human muscles would create a super athlete?Knocking out a particular gene in muscle lets mice run twice as far as normal. Knocking out the same gene in fat cells allows the animals to put on weight without developing type-2 diabetes.

The discoveries could lead to new treatments for diabetes or for invigorating muscles in elderly people and in those with wasting diseases, say Johan Auwerx of the Federal Polytechnic School of Lausanne, Switzerland, and colleagues.

...Auwerx and his colleagues used a targeted virus to knock out the gene that makes a protein called nuclear receptor corepressor 1 (NCoR1) in the muscle of mice. Without NCoR1, mitochondria, which power cells, keep working at full speed. "Effectively, the mice go further, faster, on the same amount of gas," says Auwerx.

"The treated mice ran an average of 1600 metres in 2 hours, compared with 800 metres for untreated mice," he says.

...Auwerx warns athletes not to try to grow their muscles and stamina illicitly by somehow targeting the NCoR1 protein, however.

"We only know what happens if it's knocked out either in fat or muscle, and it could have serious side effects on other organs," he says. Also, he points out that without NCoR1, all fetuses perish, so it plays a vital but undiscovered role in fetal development. _NewScientist
Right. As if Auwerx' warnings would have any effect on a determined athlete's plans. And there are likely several other ways for athletes to tweak their muscles' genes, to gain an advantage.
One gene, for example, called MYH16, contributes to the development of large jaw muscles in other apes. In humans, MYH16 has been deactivated. (Puny jaws have marked our lineage for as least 2 million years.) Many people have also lost another muscle-related gene called ACTN3. People with two working versions of this gene are overrepresented among elite sprinters while those with the nonworking version are overrepresented among endurance runners. _Slate
More muscle boosting genes:

CNTF 1357 G → A polymorphism and the muscle strength response to resistance training Jnl Appl Physio 2009

Follistatin Gene Delivery Enhances Muscle Growth and Strength in Nonhuman Primates Sci Transl Med 2009

Long-term enhancement of skeletal muscle mass and strength by single gene administration of myostatin inhibitors PNAS 2008

Increased muscle PGC-1α expression protects from sarcopenia and metabolic disease during aging PNAS 2009

Genetically boosted athletes are inevitable, once stealth techniques of controlling gene expression and transfer are developed. But that also means that viable means of strengthening the muscles, bones, and other tissues that normally weaken with ageing, will also be within reach. So it's best not to complain too loudly about the athletes who tweak themselves for advantage, so long as the rest of us can win in the game of life.

Abstract from Cell:

Transcriptional coregulators control the activity of many transcription factors and are thought to have wide-ranging effects on gene expression patterns. We show here that muscle-specific loss of nuclear receptor corepressor 1 (NCoR1) in mice leads to enhanced exercise endurance due to an increase of both muscle mass and of mitochondrial number and activity. The activation of selected transcription factors that control muscle function, such as MEF2, PPARβ/δ, and ERRs, underpins these phenotypic alterations. NCoR1 levels are decreased in conditions that require fat oxidation, resetting transcriptional programs to boost oxidative metabolism. Knockdown of gei-8, the sole C. elegans NCoR homolog, also robustly increased muscle mitochondria and respiration, suggesting conservation of NCoR1 function. Collectively, our data suggest that NCoR1 plays an adaptive role in muscle physiology and that interference with NCoR1 action could be used to improve muscle function. _Cell

Would You Trade Places With a Naked Mole Rat?

2011-11-17T00:39:00.000-08:00

the naked mole rat has what could be the most extraordinary set of natural defenses ever found in a mammal. A mouse's life is short and terrible—even in the lab, with plenty of food and a steady thermostat, it lasts for just three or four years at the most. A naked mole rat shows no sign of aging until it's a quarter of a century old. Blind and plump, it skitters around in a hazmat suit of its own creation. _Slate
Naked mole rats appear impervious to radiation and carcinogens of all kinds. These naked mole rats are incredibly reluctant to get cancer. And that is not the half of it:In 2004, Buffenstein and her students tried one of these shortcuts. They placed some mole rats in a gamma chamber and blasted their pale, pink bodies with ionizing rays. The animals were unimpressed. When I visited Buffenstein’s lab this past July, many were still alive, skittering through the plastic tubes of their basement habitat at the Barshop Institute for Longevity and Aging Studies.

Four years later, Buffenstein...infected cells from a naked mole rat with a virus designed to corrupt their nuclei with the cancer-causing genes SV40 TAg and Ras. Then she slipped those cells into a live mouse, under the skin behind its ear. If you do the same using infected material from a mouse or a rat, or even a cow or a human, the transplant quickly grows into a deadly tumor, invading nearby fat and muscle tissue. But when Buffenstein and her colleagues used cells from a naked mole-rat, nothing happened.

...Earlier this year, one of Buffenstein's graduate students tried smearing the skin of half a dozen naked mole rats with a pair of vicious carcinogens: A synthetic compound called DMBA and an inflammatory agent known as TPA. When the same toxic pairing was applied to regular Black-6 lab mice as an experimental control, a cluster of tumors popped up within weeks. Every single mouse had cancer, and every single mouse died. The naked mole rats went on skittering through their tubes.

...Her latest assault involves pouring carcinogens down the mole rats' throats in a last-ditch effort to induce liver or mammary cancer. But that may not work, either. For years, Buffenstein's laboratory Rasputins have been irradiated, poisoned, and heated up; their cells dosed with every imaginable pollutant—chemotherapies, oxidative stressors, and heavy metals—with little or no effect. "You name it," the professor says, "we tried all the kinds of toxins that are out there, and the naked mole rat seems to be very resilient and resistant."

...The very thing that makes naked mole rats so interesting to Buffenstein—an astonishing vitality that lasts for decades—only makes her research more difficult. "You're caught between a rock and a hard place, because they live so long that your grandchildren have to finish the studies you start." Still, slow science may have rich rewards, and the decisions we make today—on whether to invest in new model organisms or build out the ones we already have—are sure to have profound effects on the (human) generations to come. _Slate
The above Slate article by Daniel Engber is an excellent example of good science writing. We learn about the things that make the naked mole rat intriguing as an object of study, then we learn why the biomedical funding establishment is so biased against funding studies using naked mole rats. The life of science is full of such conflicts, which can drive scientists out of the lab entirely if they cannot learn to deal with the frustrating politics and grant grubbing.

No human would want to trade places with a naked mole rat, even if it meant living 10 times longer -- and in better health -- than the average human. But we might want some of the naked rats resistance to cancer and degenerative change.

Human gerontologists are not trying to discover the path to immortality. They are not even trying to give humans the relative advantage in life span that the naked mole rat has over other rodents. What human scientists are trying to achieve is fairly modest -- they want to find a way to delay the signs of aging for roughly seven years beyond the average:THE TARGET What we have in mind is not the unrealistic pursuit of dramatic increases in life expectancy, let alone the kind of biological immortality best left to science fiction novels.20 Rather, we envision a goal that is realistically achievable: a modest deceleration in the rate of aging sufficient to delay all aging-related diseases and disorders by about seven years.21 This target was chosen because the risk of death and most other negative attributes of aging tends to rise exponentially throughout the adult lifespan with a doubling time of approximately seven years.22 Such a delay would yield health and longevity benefits greater than what would be achieved with the elimination of cancer or heart disease.23 And we believe it can be achieved for generations now alive.

If we succeed in slowing aging by seven years, the age-specific risk of death, frailty, and disability will be reduced by approximately half at every age. People who reach the age of 50 in the future would have the health profile and disease risk of today’s 43-year-old; those aged 60 would resemble current 53-year-olds, and so on. Equally important, once achieved, this seven-year delay would yield equal health and longevity benefits for all subsequent generations, much the same way children born in most nations today benefit from the discovery and development of immunizations.

A growing chorus of scientists agrees that this objective is scientifically and technologically feasible. How quickly we see success depends in part on the priority and support devoted to the effort. Certainly such a great goal – to win back, on average, seven years of healthy life – requires and deserves significant resources in time, talent and treasury. But with the mammoth investment already committed in caring for the sick as they age, and the pursuit of ever-more expensive treatments and surgical procedures for existing fatal and disabling diseases, the pursuit of the Longevity Dividend would be modest by comparison. In fact, because a healthier, longer-lived population will add significant wealth to the economy, an investment in the Longevity Dividend would likely pay for itself. _"TheScientist"_via_NR
Can we learn anything toward that end, from the naked mole rat? Quite possibly. But we have to be willing to put in the time and expense to learn how to transfer the lessons from that exceptional rodent to the human species.

Cognitive Enhancers In Health and Disease

2011-11-16T11:47:00.000-08:00

Cognitive enhancer	Neuromodulatory mechanism	Cognitive functions improved	Known brain systems most affected	Currently recommended clinical use
Methylphenidate, amphetamine	Dopamine and noradrenaline reuptake inhibitors	Response inhibition, working memory, attention, vigilance	Frontoparietal attentional systems, striatum, default mode networks	ADHD, wake-promoting agent
Caffeine	Non-selective adenosine receptor antagonist	Vigilance, working memory, incidental learning	Frontal lobe attentional systems	–
Nicotine	Nicotinic cholinergic receptor agonist	Working memory, episodic memory, attention	Fronto-parietal attentional systems, medial temporal lobe, default mode networks	–
Modafinil	Unknown, but effects on dopamine, noradrenaline and orexin systems proposed	Working memory, episodic memory, attention	Frontal lobe attentional systems	Wake-promoting agent
Atomoxetine, reboxetine	Noradrenaline reuptake inhibitors	Response inhibition, working memory, attention	Frontoparietal attentional systems	ADHD, depression
Donepezil, galantamine, rivastigmine (AChEI)	Blocks enzymatic breakdown of acetylcholine	Episodic memory, attention	Frontal lobe attentional systems	Alzheimer's disease, PDD, DLB
Memantine	Noncompetitive, low-affinity, open channel blocker of the NMDA receptor	Episodic memory, attention	Frontal and parietal lobe	Alzheimer's disease

Table SourceThe ongoing process of ageing in all advanced societies around the world presents the unhappy prospect of a veritable global epidemic of Alzheimer's and other neurodegenerative conditions. Such an ominous prospect makes the quest for cognitive enhancers somewhat urgent, for all modern nations. We will look at the nature of current cognitive enhancers, and consider the prospects for future enhancers of cognition. The focus will be on long-term enhancement and neuroprotection, rather than the short-term performance enhancers which are popular on college campuses.
It would probably be fair to say that we are still in the first generation of studies to examine the potential for cognitive enhancement in humans. In both healthy individuals and many patient groups, the overall effects of drugs generally seem to be modest. However, there is evidence that there might be more significant effects in subgroups, such as those whose baseline performance is poorest or individuals with a particular genotype. Moreover, new drugs aimed at enhancing the phasic response of neurotransmitter systems, such as direct nicotinic agonists for the cholinergic system [34], might prove to have greater effects than existing modulators that globally increase levels of a neurotransmitter in a tonic fashion. The neurobiology underpinning the effects of cognitive enhancers and the mechanisms that determine responsiveness across individuals promise to be the focus of research in health and brain disorders in the future. _Source
The ongoing study of current cognitive enhancers such as those in the table above, have given us scattered hints as to what future therapies might offer. Here is a short list of possible future targets for cognitive therapies:Among targets under investigation, cholinergic receptors have received much attention with several nicotinic agonists (α7 and α4β2) actively in clinical trials for the treatment of AD, CIAS and attention deficit hyperactivity disorder (ADHD). Both glutamatergic and serotonergic (5-HT) agonists and antagonists have profound effects on neurotransmission and improve cognitive function in preclinical experiments with animals; some of these compounds are now in proof-of-concept studies in humans. Several histamine H3 receptor antagonists are in clinical development not only for cognitive enhancement, but also for the treatment of narcolepsy and cognitive deficits due to sleep deprivation because of their expression in brain sleep centers. Compounds that dampen inhibitory tone (e.g., GABAA α5 inverse agonists) or elevate excitatory tone (e.g., glycine transporter inhibitors) offer novel approaches for treating diseases such as schizophrenia, AD and Down syndrome. In addition to cell surface receptors, intracellular drug targets such as the phosphodiesterases (PDEs) are known to impact signaling pathways that affect long-term memory formation and working memory. Overall, there is a genuine need to treat cognitive deficits associated with many neuropsychiatric conditions as well as an increasingly aging population. _Source
It is important for us, at the outset, to take as realistic a viewpoint toward the possibility of meaningful cognitive enhancement as possible. The Likelihood of Cognitive Enhancement (Lynch et al 2011 PDF) is a useful introduction to many of the practical issues that need to be faced from the very beginning of this enterprise. Cognitive Enhacement: Promises and Perils (Hyman 2011 PDF) is a less technical introduction to the topic, perhaps more accessible to most laymen.

Cognitive Enhancement as a Pharmacotherapy Target for Stimulant Addiction (Sofuoglu 2010) looks at the use of cognitive enhancers as possible treatments for cocaine and methamphetamine addictions. Long term and heavy use of these drugs leads to cognitive deficits which make it even more difficult for a person to stop using these drugs and lead a "normal" life. The restoration of cognitive function is likely to provide a certain amount of "mental fortification" to allow at least some addicts to turn away from the dead end lifestyle. Similarly, restoration of cognitive function in persons suffering from age-related neurodegeneration is more likely to allow the person to participate in normal social interaction, and to undertake some level of responsibility, and perhaps productive activity.

Emerging Pharmacotherapies for Neurodevelopmental Disorders (Wetmore et Garner 2010) looks at the use of cognitive enhancers for persons who suffer from neurodevelopmental disorders such as Down's Syndrome, Fragile X, autism, etc. Given the overlap of mechanisms between some of the cognitive deficits in developmental disorders and ageing-related cognitive deficits, some of the coming developments in this area of pharmacotherapy should also prove quite helpful for treating age-related dementias.
As more is learned about the time-course of dysfunction in NDDs [neurodevelopmental disorders], targeting of therapies to the existing brain state may be improved. Moreover, individuals with NDDs have multiple cognitive and behavioral disabilities, and a particular drug therapy may improve only a subset of cognitive functions. Thus, a combination of complementary drugs may offer the most benefit by addressing deficits in attention, arousal, information processing, or depression.
...
The NDDs discussed here are phenotypically diverse yet linked by common mechanisms of dysfunction, including abnormal gene dosage, imbalance among neurotransmitter systems, and local protein translation (Fig. 2). A particular NDD can be caused by mutations in multiple genes, underscoring the convergence of dysfunction in key biochemical pathways. _Source
Finally, I would like to append to this entry some material from an earlier Al Fin article, which provides a few hints of future drug targets, as well as links to related material:

AMPAkines
CREB
PDE Inhibitors(4,10)
Nicotinic Alpha-7 agonists
mGluR antagonists
5HT6 antagonists

Frontrunners in the pharmaceutical race for smarter, better memory drugs include Memory Pharmaceuticals, Cortex Pharmaceuticals, Saegis Pharmaceuticals, Helicon, Lilly, Pfizer, Wyeth, Merck, Sention and many others. The precedent of approving drugs for erectile dysfunction (ED)--a lifestyle drug--suggests that smart drugs will eventually be approved for drooping memories as well.

Further Reading:

Molecules for Memory

Nootropics

Smart Drugs: What Are the Prospects?

Shaping the Brain with Smart Drugs (Gazzaniga)

CREB and Memory (basic neuroscience)

CREB, Synapses, and Memory Disorders

Hat tip Advanced Nano and Kurzweilai.net

Stem Cell Research Starting to Pay Off

2011-11-14T19:20:00.000-08:00

A total of 23 patients took part in the ''Scipio'' trial, all of whom had suffered heart failure due to a previous heart attack. Sixteen were assigned to the stem cell therapy while the other seven received standard care.

...The ground-breaking new treatment involved extracting cardiac stem cells (CSCs) - self-renewing cells that rebuild hearts and arteries - from patients during bypass surgery.
The cells were purified and grown in the laboratory before being injected back into damaged regions of the patients' hearts four months later.

A million CSCs were infused into each patient via a balloon catheter, an expandable device used to open up arteries.

Heart pumping efficiency is assessed by measuring the fraction of blood expelled or ''ejected'' from the left ventricle with each beat.

At the start of the study, the patients had an average left ventricular ejection fraction (LVEF) of 40% or lower. Normal LVEF is 50% or higher.

Over a period of four months patients who underwent the treatment saw an 8.5% improvement in LVEF. After one year, this increased to 12.3%. LVEF did not change in the seven ''control'' patients who did not receive the therapy.

The findings were published today in an online edition of The Lancet medical journal. They were also presented at the American Heart Association's Scientific Sessions meeting in Orlando, Florida.

Magnetic Resonance Imaging (MRI) scans conducted on a number of patients showed that scarring in their hearts had been reduced.

The small Phase I study was primarily designed to assess safety rather than effectiveness. _Telegraph
As noted, the study was a "Phase I" clinical study meant to determine the safety of the treatment. In later, Phase II studies, efficacy will be looked at more closely. The results from this trial are quite encouraging -- modest but significant -- allowing a greater range of activity for the treatment group, post trial.

More from Genetic Engineering News:Stage A of the ongoing open-label Phase I SCIPIO (Stem Cell Infusion in Patients with Ischemic cardiOmyopathy) study, by investigators at the University of Louisville and Brigham and Women’s Hospital, is evaluating CSC transplantation in patients with severe heart failure secondary to ischemic cardiomyopathy. The target population includes patients who underwent coronary artery bypass grafting (CABG), had LV ejection fraction (EF) of less than or equal to 40%, and a previous myocardial infarction.

Treated patients were administered with about a million autologous CSCs by intracoronary infusion, at a mean of 113 days after CABG. To generate the cardiac stem cells, tissue from the right atrial appendage was harvested from the patients at the time of CABG, and CSCs were isolated and expanded at the Brigham and Women’s Hospital.

...The trial has been led by Roberto Bolli, M.D., at the University of Louisville and Piero Anversa, Ph.D., at Brigham and Women's Hospital/Harvard Medical School in Boston. "The results are striking," Dr. Bolli states. "While we do not yet know why the improvement occurs, we have no doubt now that ejection fraction increased and scarring decreased. If these results hold up in future studies, I believe this could be the biggest revolution in cardiovascular medicine in my lifetime."

The published paper in The Lancet is titled "Cardiac stem cells in patients with ischaemic cardiomyopathy (SCIPIO): initial results of a randomised Phase I trial.” _GenEngNews
Heart muscle is relatively uncomplicated, as far as vital organs go, so it is not a great surprise that such a simple stem cell replacement therapy might work. Liver and pancreas may be similarly amenable to simple stem cell infusion. But other organs will require more clever designs for creating replacement tissue from stem cells and scaffolding.

In terms of numbers of persons potentially affected by this therapy for heart failure, the number will easily go into the millions in North America alone. Optimal therapy may require multiple infusions over time, to allow the heart to assimilate the new cells. More will be known as the research progresses into further stages.

This is just the beginning.

Rejuvenating 100 Year Old Cells: Advances in Regenerative Medicine

2011-11-07T07:11:00.000-08:00

"Signs of aging were erased and the iPSCs obtained can produce functional cells, of any type, with an increased proliferation capacity and longevity," explains Jean-Marc Lemaitre who directs the Inserm AVENIR team....The age of cells is definitely not a reprogramming barrier. _SD

Cell Rejuvenation via IPSC
Scientists at the Functional Genomics Institute have taken cells donated by persons older than 100 years, and reprogrammed these senescent cells into pluripotent stem cells and embryonic stem cells. These stem cells can then be differentiated into specialised cells for cell, tissue, and organ replacement therapy -- once the details are worked out.

The researchers have successfully rejuvenated cells from elderly donors, some over 100 years old, thus demonstrating the reversibility of the cellular aging process.

To achieve this, they used an adapted strategy that consisted of reprogramming cells using a specific "cocktail" of six genetic factors, while erasing signs of aging. The researchers proved that the iPSC cells thus obtained then had the capacity to reform all types of human cells. They have the physiological characteristics of "young" cells, both from the perspective of their proliferative capacity and their cellular metabolisms.

Researchers first multiplied skin cells (fibroblasts) from a 74 year-old donor to obtain the senescence characterized by the end of cellular proliferation. They then completed the in vitro reprogramming of the cells. In this study, Jean-Marc Lemaitre and his team firstly confirmed that this was not possible using the batch of four genetic factors (OCT4, SOX2, C MYC and KLF4) traditionally used. They then added two additional factors (NANOG and LIN28) that made it possible to overcome this barrier.

Using this new "cocktail" of six factors, the senescent cells, programmed into functional iPSC cells, re-acquired the characteristics of embryonic pluripotent stem cells.
In particular, they recovered their capacity for self-renewal and their former differentiation potential, and do not preserve any traces of previous aging. To check the "rejuvenated" characteristics of these cells, the researchers tested the reverse process. The rejuvenated iPSC cells were again differentiated to adult cells and compared to the original old cells, as well as to those obtained using human embryonic pluripotetent stem cells (hESC).

...The results obtained led the research team to test the cocktail on even older cells taken from donors of 92, 94 and 96, and even up to 101 years old. "Our strategy worked on cells taken from donors in their 100s. The age of cells is definitely not a reprogramming barrier." He concluded. "This research paves the way for the therapeutic use of iPS, insofar as an ideal source of adult cells is provided, which are tolerated by the immune system and can repair organs or tissues in elderly patients." adds the researcher.

...Inserm's AVENIR "Genomic plasticity and aging" team, directed by Jean-Marc Lemaitre, Inserm researcher at the Functional Genomics Institute (Inserm/CNRS/Université de Montpellier 1 and 2) performed the research. The results were published in Genes & Development on November 1, 2011 _SD

The first use of this new regenerative technology is likely to be cell replacement therapy. But as the methods for growing replacement tissues and organs in the lab are perfected, the methods should be suitable for producing cells to use in growing replacement tissues and organs for purposes of disease treatment and for treating senescence.

Cross-posted from Al Fin

Two Hints of the Possibility for a Healthy Long Life

2011-11-03T16:36:00.000-07:00

The first hint comes from the Mayo Clinic's Darren Baker. Baker has developed a way of delaying symptoms of old age in mice, and has even been able to reverse some signs of aging in already aged mice. Here's more:Baker has developed a way of killing all of a mouse’s senescent cells by feeding them with a specific drug. When he did that in middle age, he gave the mice many more healthy years. He delayed the arrival of cataracts in their eyes, put off the weakening of their muscles, and held back the loss of their body fat. He even managed to reverse some of these problems by removing senescent cells from mice that had already grown old. There is a lot of work to do before these results could be applied to humans, but for now, Baker has shown that senescent cells are important players in the ageing process.

Note that the mice in this study didn’t live any longer; they just spent more of their life being healthy.

Baker exploited the fact that many senescent cells rely on a protein called p16-Ink4a. He created a genetic circuit that reacts to the presence of p16-Ink4a by manufacturing an executioner: a protein called caspase-8 that kills its host cell. Caspase-8 is like a pair of scissors – it comes in two halves that only work when they unite. Baker could link the two halves together using a specific drug. By sneaking the drug into a mouse’s food, he activated the executioners, which only killed off the cells that have lots of p16-Ink4a. Only the senescent ones get the chop.

Baker tested out this system in a special strain of genetically engineered mice that age very quickly. It worked. The senescent cells disappeared, and that substantially delayed the onset of muscle loss, cataracts, and fat loss. Typically, around half of these mice show signs of muscle loss by five months of age. Without their senescent cells, only a quarter of them showed the same signs at ten months. Their muscle fibres were larger, and they ran further on treadmills. Even old mice, whose bodies had started to decline, showed improvements. _Discover
Another look at this research from the Economist:Dr Baker genetically engineered a group of mice that were already quite unusual. They had a condition called progeria, meaning that they aged much more rapidly than normal mice. (A few unfortunate humans suffer from a similar condition.) The extra tweak he added to the DNA of these mice was a way of killing cells that produce P16INK4A. He did this by inserting into the animals’ DNA, near the gene for P16INK4A, a second gene that was, because of this proximity, controlled by the same genetic switch. This second gene, activated whenever the gene for P16INK4A was active, produced a protein that was harmless in itself, but which could be made deadly by the presence of a particular drug. Giving a mouse this drug, then, would kill cells which had reached their Hayflick limits while leaving other cells untouched. Dr Baker raised his mice, administered the drug, and watched.

The results were spectacular. Mice given the drug every three days from birth suffered far less age-related body-wasting than those which were not. They lost less fatty tissue. Their muscles remained plump (and effective, too, according to treadmill tests). And they did not suffer cataracts of the eye. They did, though, continue to experience age-related problems in tissues that do not produce P16INK4A as they get old. In particular, their hearts and blood vessels aged normally (or, rather, what passes for normally in mice with progeria). For that reason, since heart failure is the main cause of death in such mice, their lifespans were not extended.

The drug, Dr Baker found, produced some benefit even if it was administered to a mouse only later in life. Though it could not clear cataracts that had already formed, it partly reversed muscle-wasting and fatty-tissue loss. Such mice were thus healthier than their untreated confrères. _Economist
This research will require replication and a great deal of clarification, before it moves from mice to larger mammals such as humans. But it opens up a number of possible avenues of research.

The second hint of likely means to achieve healthier long lives, is research done in fruit flies at the Salk Institute, in southern California.
Although it is a well-documented fact that restricting calories during daily food intake is the easiest strategy to extend life spans for both humans and animals, little is known about biological mechanisms underlying this phenomenon.

..."Fruit flies and humans have a lot more in common than most people think," said Leanne Jones, an Associate Professor at Salk's Laboratory of Genetics and a lead scientist on the project, "There is a tremendous amount of similarity between a human small intestine and the fruit fly intestine."

The researchers found that boosting the activity of dPGC-1, the Fruit Fly version of the gene, resulted in greater numbers of mitochondria and more energy-production in flies; the same phenomenon is seen in organisms on calorie restricted diets.

When the activity of the gene was accelerated in stem and progenitor cells of the intestine, which serve to replenish intestinal tissues, these cellular changes correspond with better health and longer lifespan.

The flies lived between 20 and 50 percent longer, depending on the method and extent to which the activity of the gene was altered. _ibtimes
The fruit fly research suggests that not only healthier long lives are possible, but "longer long" lives are possible as well.

The approach taken by the SENS Foundation involves using multiple approaches to extending healthy lifespan. Destroying senescent cells -- such as Darren Baker is learning to do -- is one of the main approaches that SENS is following. Improving the function of mitochondria is another of the main tactics of SENS.

As humans in advanced societies are putting less and less energy into raising children, and putting more and more energy into raising themselves, thoughts of increased longevity and lifespan are coming more into the mainstream of respectability. The main limitation to further research into life extension is -- as always -- funding. But even with unlimited funding, moving the research from animal models into human therapeutics would take a matter of decades.

The Mystery of Epigenetic Heredity, and Its Possible Impact on Longevity

2011-10-19T12:04:00.000-07:00

The basic mechanisms of life and inheritance function much the same in worms, fruit flies, mice, and humans. That is one reason why lower life forms are used so often in longevity research. Much shorter lifespans is another reason. A recent Stanford study on worms provides a hint at an epigenetic method of inheritance which may eventually prove useful for extending lifespans in human offspring.
The study used Caenorhabditis elegans worms with very low levels of the SET-2 enzyme. The SET-2 enzyme normally adds methyl molecules onto DNA's protein packaging material. In doing so, the enzyme opens up the packaging material, allowing the genes to be copied and expressed. Some of those genes appear to be pro-aging genes, says Brunet. Her team knocked out SET-2 by removing genes that code for it. This had the effect of significantly lengthening the worms' lifespan, presumably because those pro-aging genes were no longer expressed.

Next, the long-lived, enzyme-lacking worms mated with normal worms. The offspring had the regular genes for making SET-2, and even expressed normal amounts of the enzyme, but they lived significantly longer than control worms whose parents both had regular lifespans. The life-extending effect carried over into the third generation, but returned to normal by the fourth generation (in the great-grandchildren of the original mutant worms). For the first few generations, having a long-lived ancestor increased life expectancy from 20 days to 25, extending a worm's life by 25 to 30 percent on average.

Brunet and her team haven't yet determined the exact mechanism for the lifetime extension, or which molecules are at work. This is one of the study's imperfections, says David Katz, who researches epigenetic transcriptional memory at Emory University. Regardless, "the effect is clearly epigenetic," he says, "and it's probably one of the most complicated traits that has been linked to epigenetic inheritance."

...The results, published October 19 in Nature (Scientific American is part of Nature Publishing Group), provide the first evidence that some aspects of lifespan length can be passed from parent to offspring, independent of the direct influence DNA. _SciAm
Contrary to what Dr. Katz asserts above, the fact that the research team hasn't determined the exact mechanism for the lifetime extension is one of the study's great promises.

Remember, it is often the questions that a study raises which causes the study to become frequently cited, and immortalised -- not necessarily the questions the study answers. Studies that raise good questions often act as springboards for entire new developments in science. Such may be the case here.

What Supplements Should Be Taken to Preserve the Brain?

2011-10-09T09:19:00.000-07:00

A recent study published in the Journal of Intelligence looked at the effects on IQ of a proprietary combination of nutritional supplements, called Ceretrophin, vs. placebo. The combination is made up of Huperzine A, Vinpocetine, Acetyl-l-carnitine, R. Rosea and Alpha-lipoic acid, all readily available over the counter in the US. The researchers tested the subjects on Ravens Advanced Progressive Matrices (APM) prior to treatment and after 4 weeks of treatment or placebo.
A significant study visit (time) treatment condition interaction was found: F (1, 57) = 7.279, p = 0.009, partial 2 = .113, with paired samples t-tests revealing a significant improvement in mean APM score from baseline to retest (week 4) (t(34) = 4.045, p < .001) for the Ceretrophin group. Improvements in APM scores could be attributed to the active intervention over the placebo, indicating that the treatment improved general intelligence. Implications for improving our understanding of the biological basis of intelligence and pharmacologically improving human cognition are discussed. _Intelligence_via_Inductivist
Ron Guhname at the Inductivist blog suggests that this improvement in Ravens APM scores represents an increase in IQ score of 6 points (see comment at link).

The assortment of supplements included in "Ceretrophin" provides a wide spectrum of effects on neural tissues, including anti-inflammatory, stimulant, vascular, and neuroreceptor effects.

In addition to the supplements listed, there are a number of others which should be considered, including curcumin and omega 3 fatty acids. It would be easy to go overboard on taking supplements, so make sure that you find a good justification for each supplement that you choose to take. Also keep in mind possible interactions between supplements, between supplements and any drugs you may take, an any potential of supplements to exacerbate a pre-existing condition you may have.

In general, the doses of supplements and herbs available OTC in pills and capsules in western nations, should not represent significant risk to most individuals.

Al Fin gerontologists and cognitive scientists do not dispute the findings in the study, although they feel the sample size was too small for definitive conclusions. Nevertheless, the study suggests that similar research with larger sample sizes and a variety of supplement combinations could be justified.

Brain Implants are Coming: Can They Repair Stroke Damage?

2011-09-27T08:47:00.000-07:00

Recent research on rats at Tel Aviv University is offering hope that we may soon have access to brain implants which could help to bypass damaged areas of brain, and allow relatively normal functioning after stroke and other types of brain damage.
Matti Mintz of Tel Aviv University in Israel and his colleagues have created a synthetic cerebellum which can receive sensory inputs from the brainstem - a region that acts as a conduit for neuronal information from the rest of the body. Their device can interpret these inputs, and send a signal to a different region of the brainstem that prompts motor neurons to execute the appropriate movement.

"It's proof of concept that we can record information from the brain, analyse it in a way similar to the biological network, and return it to the brain," says Mintz, who presented the work this month at the Strategies for Engineered Negligible Senescence meeting in Cambridge, UK.

...The team analysed brainstem signals feeding into a real cerebellum and the output it generated in response. They then used this information to generate a synthetic version on a chip that sits outside the skull and is wired into the brain using electrodes.

To test the chip, they anaesthetised a rat and disabled its cerebellum before hooking up their synthetic version. They then tried to teach the anaesthetised animal a conditioned motor reflex - a blink - by combining an auditory tone with a puff of air on the eye, until the animal blinked on hearing the tone alone. They first tried this without the chip connected, and found the rat was unable to learn the motor reflex. But once the artificial cerebellum was connected, the rat behaved as a normal animal would, learning to connect the sound with the need to blink.

...The next step is to model larger areas of the cerebellum that can learn a sequence of movements and test the chip in a conscious animal - a much greater challenge. "This is very demanding because of the decrease of [neural] signal quality due to artefacts caused by movement," says Robert Prueckl of Guger Technologies in Graz, Austria, who is working with Mintz. He thinks this can be achieved, though, by developing improved software to tune out noise and better techniques for implanting the electrodes. Ultimately, the goal is to build chips that can replicate complex areas of the brain _NewScientist
Yes, the implant used by the researchers was only able to substitute for a small part of the cerebellum -- which is only one part of the brain. Still, it is a start. The challenge is to enlarge and consolidate this understanding of the motor system. Then we can move beyond these early victories to the far more complex and difficult challenges of substituting for more complex signaling that occurs in the cortical and subcortical tissues.

And yet it would be best not to underestimate this achievement. The cerebellum helps to control and coordinate body movement, which is a very important function of being human. Those who have lost the ability to initiate, control, coordinate, and terminate basic movements, understand how important the motor system is to quality of life.

Cyborg brain part replacement is not the end goal, of course. We really want to re-grow any damaged brain parts or nerve connections which have been lost. But cyborg replacements will be an important bridge between where we are now and where we would like to go.

IPS Stem Cells Are Looking More Promising for Regenerative Medicine

2011-09-15T19:53:00.000-07:00

George Church is a professor of genetics at Harvard Medical School. He is becoming more and more deeply involved in the field of regenerative medicine, using induced pluripotent stem cells (IPS). Church was interviewed recently on how he sees the field of IPS regenerative medicine progressing.
A pioneer in developing DNA sequencing technologies, and in researching everything from epigenetics and microbiomics to synthetic biology, Church has co-founded or advises over 20 companies. He also has launched the Personalized Genome Project with a goal of sequencing the complete genomes of 100,000 volunteers.

When I asked Church what he was most excited about right now, he answered without hesitation: "I'm thinking a lot about using regeneration as the key to treatments and keeping people healthy."

TR: You mean regeneration using stem cells?

Church: Yes, induced pluripotent stem (IPS) cells (see, "Growing Heart Cells Just for You"). This is where I'm putting almost all of my chips these days, because it combines many of my interests--genomics, sequencing, epigenetics, synthetic biology, stem cells. I don't think people have fully appreciated how quickly adult stem cells and sequencing and synthetic biology have progressed. They have progressed by orders of magnitude since we got IPS. Before that, they basically weren't working.

Is this because IPS cells are relatively easy to create and to engineer?

You can use them to reprogram genomes--not sequence them, but to reprogram them genetically and epigenetically. In other words you make the minimum changes it takes to get them where you want them to be genetically and epigenetically and then you program the cells into tissues.

What do you mean?

Let's use stem cells in bone marrow as an example. They are easy to use and to get to work when you implant them in bone marrow. You might one day have three choices. You can have bone marrow from someone else that is matched to you, or that is from you, or bone marrow that is matched to you and comes to you, but is better than you. This better bone marrow might be [engineered to be] resistant to one virus, or to all viruses. It could have a bunch of alleles that you picked out of super centenarians, alleles that you have reason to believe are at least harmless and possibly helpful. So now you have choice, a patient who can take a good bone marrow that he might reject and you'll be on immunosuppressants your whole life. Or you might use your own, or your own that might fix the cancer, or your own enhanced bone marrow. And you will be able to do that for almost every stem cell population. Some of them are a little bit harder to replace, though.

Does IPS really work to accomplish this regeneration?

We have good evidence that you can create an entire mouse from IPS cells.

Has this been done?

This has been done. They have used IPS cells to grow a mouse, and they made IPS cells from that mouse. They're totipotent [able to make an entire organism], not merely pluripotent. We haven't done this for humans for obvious ethical reasons, but we will do it. As far as I know the mice have done fine.

But haven't there been some problems with mutations occurring with IPS-generated tissue?

We have a recent paper in Nature that shows that when you make human induced pluripotent stem cells you actually do get mutations in coding regions at a slightly elevated level. But I think this is temporary. We're going to use this information as an assay to make the process work better, to correct problems. You will be able to use this to improve the quality of gene therapy because that's been the problem with gene therapy the last ten years.

How far are we from testing that in humans?

Almost everything I've described has been done in rodents, so we're talking about years, not decades. It's shorter than the Human Genome Project [which took 13 years], not less expensive, but definitely shorter. _TechnologyReview

Scientists at the University of Toronto have recently made a breakthrough in the control of IPS cells' pluripotency:Scientists have found a control switch that regulates stem cell “pluripotency,” the capacity of stem cells to develop into any type of cell in the human body. The discovery reveals that pluripotency is regulated by a single event in a process called alternative splicing.

Alternative splicing allows one gene to generate many different genetic messages and protein products. The researchers found that in genetic messages of a gene called FOXP1, the switch was active in embryonic stem cells but silent in “adult” cells—those that had become the specialized cells that comprise organs and perform functions.

“It opens the field to the fact that alternative splicing plays a really important role in stem cell pluripotency,” said Prof. Benjamin Blencowe, principal investigator on the study and a Professor in the University of Toronto’s Departments of Molecular Genetics and Banting and Best Department of Medical Research. “We’re beginning to see an entirely new landscape of regulation, which will be crucial to our understanding of how to produce more effective pluripotent stem cells for therapeutic and research applications.”

The findings were published in the current online edition of the scientific journal Cell. _Source
These are some fascinating developments, which will eventually lead to advanced therapies for diseases which are currently untreatable, such as cancers and end stage degenerative diseases of the heart, lungs, liver, kidneys, and brain.

The ability to grow replacement organs from stem cells is already being proven in animals. The ability to regenerate a badly degenerated organ in situ, using stem cells, is also being proven. According to George Church, stem cells are also the best method for making genetic improvements to organs and organisms.

BioHeart's clinical stem cell trials in Mexico

ThermoGenesis an early commercial entrant into the human stem cell regenerative medicine industry

Molecular Circuits Learn to Trigger Targeted Cancer Cell Death

2011-09-02T14:05:00.000-07:00

Discover
An international team of researchers has learned to use micro-RNA circuits to trigger targeted cell death in HeLa cells, widely used cultured cervical cancer cells, orginally taken from a woman who died long ago. Although it is too late for this information to help Henrietta Lacks, it is possible that this approach -- or something like it -- may be used to trigger the large-scale suicide of a wide range of cancer cells eventually.
Xie has developed a genetic “logic circuit” that prompts cells to kill themselves if the levels of five molecules match those of a cancer cell. Yaakov Benenson, who led the study, says, “In the long term, the circuits’ role is to act like miniature surgeons that can identify and destroy cancer cells.” That is a very long way off, but the study is a promising step in the right direction.

Xie worked with HeLa cells, a common line of cervical cancer cells taken from a tobacco farmer called Henrietta Lacks in 1951. Since then, they have become one of the most important tools in modern medicine. Xie identified five small molecules called microRNAs that act as a signature for HeLa cells, separating them from healthy ones. Two of the microRNAs are unusually common in HeLa; three are unusually rare.

Next, Xie created five genetic switches that would only flip if their respective microRNAs were found at the right levels. The switches control a gene called Bax, an executioner that compels a cell to kill itself. If the circuit is introduced into a cell that carries the molecular signature of HeLa, all five switches flip, Bax is roused into action, and the cell automatically self-destructs.

Xie rigged his circuit so that Bax could be restrained by each of the three microRNAs found at low levels in HeLa cells. The gene would only activate if all three molecules were largely absent; any one of them could stay the executioner’s hand. Meanwhile, the two microRNAs that are common in HeLa actually lift restraints on Bax, by blocking genes that keep it in check. Again, the circuit needs high levels of both of these molecules. If either is absent, Bax is held back.

This clever set up means that all five switches must to be flipped before the executioner carries out it bloody work. The cell only dies if it meets every one of five conditions. And Xie found that his circuit worked in practice. It activated Bax at far higher levels in HeLa cells and selectively killed them while leaving other lineages of laboratory cells unharmed. _Discover

Article abstract from Science

More from ArsTechnica

More from ETH Zurich via Nanowerk

Al Fin research oncologists and molecular biologists feel that Benenson's approach is more than a bit awkward and prone to breaking down. But he is working at a level of gene regulation which should prove relatively safe, as it moves closer to clinical research. And he is working at a level of complexity which should prove fertile for learning more about the molecular networks of cancer.

Expect some fascinating developments to come from this line of research.

Why Do Old Brains Prefer Young Blood?

2011-09-01T06:23:00.001-07:00

A paper published today in Nature finds that when younger mice are exposed to the blood of older mice, their brain cells behave more like those found in aging brains, and vice versa. The researchers who carried out the work also uncovered chemical signals in aged blood that can dampen the growth of new brain cells, suggesting that the decline in brain function with age could be caused in part by blood-borne factors rather than an intrinsic failure of brain cells. _TechnologyReview

Many things change in the human body as we age. Our cells lose their ability to repair incidental damage, and produce less and less energy for our ever-less efficient muscles. We produce lower levels of hormones which help us, and higher levels of chemicals that cause inflammation and cellular damage.

It has been found that young blood can reverse certain signs of aging in the circulatory systems of old mice. Now there is evidence that young blood can help rejuvenate old brains.
To arrive at the discovery, the researchers studied pairs of old and young mice that were literally joined at the hip. They used a technique called parabiosis, in which two mice are surgically joined together along the flank, which causes them to develop a shared circulatory system. The technique has been used to study the development of the blood system, and more recently has been used to investigate the effects of age by joining old and young mice.

Lead author Tony Wyss-Coray, a neuroscientist at Stanford University, says that five weeks after creating these May-December pairings, "we found striking effects both on the young and old brains." The young mice had a reduction in the production of new neurons (neurogenesis), an increase in brain inflammation, and less activity in synapses connecting neurons.

The older mice, in contrast, had an increase in new neurons, less inflammation, and greater activity at synapses. "You could almost call this a rejuvenation effect," Wyss-Coray says.

...To see whether the effect could influence behavior, they injected, in separate experiments, young mice with plasma from older mice and vice versa, and found that old plasma impaired the younger animals' ability to perform learning and memory tasks, whereas young plasma improved the abilities of older mice.

Blood cells from one mouse cannot travel into the brain of the other because of the blood-brain barrier, so the team concluded that free-floating molecules in the blood, capable of passing through, must be responsible for the effects. By comparing more than 60 chemokines—chemical messengers secreted by cells that circulate in the blood—the researchers identified several associated with the detrimental effect of old blood. Administering one of these chemicals, called CCL11, to young mice dampened neurogenesis and impaired learning and memory. CCL11 has been studied for its role in allergies and asthma, but it's not clear how it influences neurons. _TechnologyReview
Does this mean that those of us who wish to stay young will have to prey on our young like vampires, sucking their life's blood for our own sustenance? No. For we are learning how to take our old cells and make them young again, in vitro -- in the test tube. The goal is to do the same thing, only better, and in vivo.

Such cellular rejuvenation treatments are likely to excellent stopgap methods of anti-aging, with significant -- but limited -- effects. The lifespans we live will be lived as younger, more vital monkey-men. And that is worth a very great deal.

But if we wish to live significantly longer lives, at significantly higher levels of awareness, intellect, and invention, we will need to go deeper than cellular replacement and humoral replacement therapies of this type.

Extending Brain Plasticity and Learning into Later Life

2011-08-18T08:30:00.000-07:00

Dendrites integrate synaptic inputs to neurons, and their branching is thought to be related to their representational capacity [24]. Branching patterns of dendritic trees are related to the degree of compartmentalization of inputs to the cell and a stronger potential for compartmentalization (i.e. more complex branching) has been proposed to increase the representational power of the cell resulting in greater learning and memory capacity [24]. Dendritic structure appears to be regulated during development in part by calcineurin [26]. Dendritic spines, which comprise the post synaptic element of over 90% of cortical excitatory synapses, are thought to be particularly important for learning and memory [18]. _ScienceDirect

ScienceDirect
An international team of researchers from Yale, University of Zagreb, and VU University in Amsterdam, have discovered that plasticity and pruning of dendritic spines in the human prefrontal cortex continues well into adulthood, throughout the 20s.
Pasko Rakic at Yale University and colleagues at the University of Zagreb, Croatia, and the VU University Medical Center in Amsterdam, the Netherlands, have now found that the brains of adults in their 20s are still subject to synaptic pruning.

Rakic's team analysed post-mortem tissue from a brain region called the prefrontal cortex (PFC) in 32 people aged between 1 week old and 91 years. Specifically, they calculated the density of dendritic spines – the tiny projections that protrude from the neuron's long dendrites, each of which facilitates communication with other neurons through a synapse.

As expected, Rakic's team found that spine density increased rapidly during infancy, reaching a peak before the 9th birthday. It then began to fall away as pruning began. Intriguingly, though, spine density did not plateau after adolescence, as might have been expected, but continued to fall gradually until the late 20s.

Rakic says the result could be good news for those hoping to gain new skills in their third decade. The period of pruning is associated with a heightened ability to learn – whether that is in picking up language skills or understanding new concepts, he says. "You should not give up learning just because you're in your 20s – it isn't too late," he says. _NewScientist
Abstract for PNAS paper

It has been shown that in rats, age related loss of normal dendritic density in prefrontal cortical neurons, occurred at the same time as loss of experience-related dendritic plasticity.

The goal of researchers is to develop ways to extend the optimal periods of brain learning well beyond young adulthood, into middle age and beyond. A Harvard - Mass General study published in Neuroscience Letters in Jan. 2011, discusses the use of a calcineurin inhibitor -- FK 506 -- to effectively increase dendritic density in cortical pyramidal neurons (all sites) of adult rats.

Such drugs provide clues as to how dendritic plasticity in the brain is regulated, and are likely to help lead to effective ways of beating back the growing impact of Alzheimer's disease and other dementias. Interestingly, calcineurin upregulation has been implicated in Alzheimer's Disease models as being responsible for amyloid related loss of glutamate receptors and decreased dendritic spine density. In such conditions, the inhibition of calcineurin (as in FK506) might well partially reverse the Alzheimer-like effects.

The mechanisms of brain development, plasticity, and disease are highly complex. We will need to learn as much as possible about signaling pathways, genetic and epigenetic mechanisms, cytoskeletal dynamics, and a number of other cellular and intercellular activities, before we will be ready to intervene in a definitive way. But things look promising, if a bit slower than we would like.

Brain Overclocking: Living a More Intense Life

2011-07-17T12:59:00.000-07:00

Neurons recruited for local computations exhibit rhythmic activity at gamma frequencies. The amplitude and frequency of these oscillations are continuously modulated depending on stimulus and behavioral state. This modulation is believed to crucially control information flow across cortical areas....by rapidly balancing excitation with inhibition, the hippocampal network is able to swiftly modulate gamma oscillations over a wide band of frequencies. _ScienceDirect

SPIE
Besides finding ways to prolong one's life, it would be worthwhile to find ways to live one's life more intensely. We have discussed ways in which we might reduce the amount of time spent in sleep, without suffering from diminished mental or physical health. There are also everyday ways in which a person can intensify his experience of his waking time. Some examples are listed at the end of this piece.

From the neurocognitive standpoint, the concept of the controlled "overclocking" of the brain -- speeding up the functioning of brain processes so that more can be experienced and accomplished in less time -- is just coming into the realm of possiblity. The concept, once developed, will rest upon a sound understanding of brain processing and inter-brain communications.

Brain activity changes between different brain states, whether awake, asleep, drugged, etc. Besides the activation of different centers in the brain according to brain state, the actual speed (frequency) of brain activity varies with different brain states.

It is thought that synchronous oscillations involving gamma carrier waves (30 to 100 Hz) modulated by theta frequencies (4 to 8 Hz) allow multiple brain processes to occur, including the transfer of working memory to long-term memory, and the binding of different sensory or other inputs into a coherent mental image of an object or idea. In other words, the way the oscillations of the brain are organised on a moment to moment basis, is what allows us to "think" and remember. (see Working Memory: The Importance of Theta and Gamma Oscillations, Lisman, Current Biology Vol 20 No 11)Gamma oscillations are thought to transiently link distributed cell assemblies that are processing related information1, 2, a function that is probably important for network processes such as perception1, 2, 3, attentional selection4 and memory5, 6. This 'binding' mechanism requires that spatially distributed cells fire together with millisecond range precision7, 8; _Nature
The idea of a synchronous oscillator, or "clock", involved in thinking and memory suggests the possibility of "speeding up the clock" or "overclocking," analogous to the overclocking of a computer processor to achieve higher computing speeds. In reality, of course, things work much differently in the brain, and no central processing unit is available for safe and controlled overclocking.

But we do know that the top end of the gamma "carrier wave" frequency can vary between types of animals. Some kinds of insects, for example, exhibit brain synchrony at frequencies up to 200 Hz in certain circuits. (Kirschfeld PNAS USA Vol. 89, pp. 4764-4768, May 1992 Neurobiology)

Different frequencies of gamma oscillation serve to connect different brain centers, in practise. This allows for simultaneous parallel activity between multiple circuits. Therefore, when "overclocking," one must be sure not to "step on" the frequencies used by different brain circuits.

There are a number of other cautions, assuming that one had a good idea how to begin to go about ramping up gamma oscillation carrier wave frequencies in the first place. The intricacy of neuronal signaling of brain circuits should discourage any attempts to permanently alter neuronal oscillatory activity. For example, gamma frequencies are closely controlled and modulated by inhibitory interneurons. You cannot change the timing of one type of cell and expect to maintain a system of smooth communication between brain nuclei. Rather, multiple keys that control the timing of networks across the brain will have to be discovered and mastered.

Why should we bother to attempt something which will require so much work? It is possible, after all, to intensify the experience of everyday life without resorting to the extremes of genetic modification of the brain.

Below are some of the everyday means by which some persons provide themselves with temporary experiences of high intensity consciousness:

Pharmacological brain stimulants have been used for this purpose for centuries, but in general they extract a steep price from the user who does not exercise prudence. Veterans of combat can attest to the consciousness-intensifying effect of the life-or-death experience. But we are looking for something more sustainable and less risky. Sky-diving, hang gliding, scuba diving, whitewater kayaking, etc. are less risky than combat, but provide a temporary aura of intensity which lingers after the experience. In occupational settings, life or death emergencies attended to by firefighters, police officers, EMS personnel, medical personnel in hospitals, etc. provide temporary "fixes" of intensity. And under the category of "not to be recommended," the commission of a crime and the attendant risk of being caught supplies the outlaw with a feeling of intensity which can become addictive to some. Similarly, committing acts which may be legal but which are socially or occupationally frowned upon, can sometimes provide a touch of that "outlaw intensity," that accompanies risk.

Perhaps the most dangerous method of intensifying experience is to fall in love. The fallout from such a turn is apt to be fatal to any number of persons involved and in the immediate vicinity. ;-)

As for using brain science to overclock the brain, I will be exploring some of the ideas that might be tried eventually in short works of fiction on another Al Fin blog.

Regenerative Medicine, Stem Cells, Designed Evolution Machines

2011-07-13T16:03:00.000-07:00

Image via NextBigFuture
A revolution in regenerative medicine, genetic recombineering, synthetic biology, systems biology, and several other points of the biosingularity are pushing ahead despite three years of global economic downturn and counting, since the fall of 2008.

Brian Wang introduces us to the "accelerated evolution machine," pictured above.
Say hello to the evolution machine. It can achieve in days what takes genetic engineers years. So far it is just a prototype, but if its proponents are to be believed, future versions could revolutionise biology, allowing us to evolve new organisms or rewrite whole genomes with ease. It might even transform humanity itself.

...Because biological systems are so complex, it is a huge advantage to be able to tweak lots of genes simultaneously, rather than one at a time, she says. "In almost every case you'll get a different solution that's a better solution."

...By automating selection and using a few tricks, though, it should be practical to screen for far more subtle characteristics. For instance, biosensors that light up when a particular substance is produced could be built into the starting strain. "The power going forward will have to do with clever selections and screens," says Church.

As revolutionary as this approach is, Church thinks MAGE's most far-reaching potential lies elsewhere. He reckons it will be possible to use the evolution machine to make many thousands of specific changes to a cell's DNA: essentially, to rewrite genomes.

At the moment, making extensive changes to even the smallest genome is extremely costly and laborious. Last year, the biologist and entrepreneur Craig Venter announced that his team had replaced a bacterium's genome with a custom-written one (Science, vol 329, p 52). His team synthesised small pieces of DNA with a specific sequence, and then joined them together to create an entire genome. It was an awesome achievement, but it took 400 person-years of labour and cost around $40 million.

MAGE can do the same job far more cheaply and efficiently by rewriting existing genomes, Church thinks. The idea is that instead of putting DNA strands into the machine with a range of different mutations, you add only DNA with the specific changes you want. Even if you are trying to change hundreds or thousands of genes at once, after a few cycles in the machine, a good proportion of the cells should have all the desired changes. This can be checked by sequencing.

...As the technology improves and becomes routine, says Church, it could also be used to alter the cells used for cell-based therapies. Tissue-engineered livers grown from stem cells, say, could have their genetic code altered so that they would be immune to liver-destroying viruses such as hepatitis C. _NewScientist_via_NBF

The "evolution machine" has its work cut out for it, but it may very well speed up some projects which do not depend upon significant transformations of the genome. More sizeable genomic transforms are not likely to be possible using such a simplist approach. But future generations of such machines are likely to grow sophisticated enough to make the work of future Craig Venters much faster and simpler.
Researchers at the LA Children's Hospital built a fully functioning artificial small intestine in mice.

A man from Eritrea was recently given an artificial trachea transplant in Sweden. The trachea was grown on a scaffold inside a bioreactor.

Scientists have isolated the human blood cell progenitor stem cell, which is capable of growing all the various cellular components of the blood system.

Johns Hopkins researchers have identified a "super neural precursor stem cell" which can not only differentiate into specialised brain cells, but can also reproduce itself!

A partial list of companies involved in regenerative medicine research and development

The US has been the world's driver of scientific and biomedical R&D for several decades now. There has been some question as to how long American research could maintain its drive, if the nation's economy was dragged down by dysfunctional governmental economic and regulatory policies. Yet, despite the current US government's apparent war against the private sector, some areas of private R&D are still thriving -- although not as well as prior to the fall of 2008.

It is vital that private sector financing be central to advanced R&D, to prevent the type of politicisation of science which has frozen climatology in an infantile state of biased activism (via GWPF), rather than dispassionate observation and honest hypothesis testing.
Federal domination of science funding has two quite intended consequences: both individual scientists and major universities have become wards of Washington. For decades, academic sociologists have noted that almost all faculty party affiliations are with the Democrats. This is no conspiracy–it is merely like-minded individuals hiring other like minds and voting their best interest. _Forbes

Previously published at Al Fin

New Findings in the Control of Stem Cell Differentiation

2011-06-26T06:11:00.000-07:00

Nodal Activin Pathways Image Source
Researchers from the Genome Institute of Singapore have helped to untangle how stem cells might be controlled with a single signaling pathway -- the nodal activin pathway.
Morphogens are secreted signaling molecules that orchestrate the spatial distribution and sequence of cellular differentiation events throughout embryonic development. The specific cell types, their localization and order of induction from recipient stem cell populations are determined by the concentration gradient of morphogens diffusing from the source of secretion. Previous studies have proposed some of the models by which morphogen gradients are initiated, established and stabilized including the level of receptor occupancy, positive/negative feedback and feed forward mechanisms [1]–[3]. However, little is understood about the transcriptional mechanisms responding to variable receptor activation and how they permit pluripotent stem cells to interpret signaling levels and direct the appropriate differentiation programs during mammalian development....

Nodal and Activin are morphogens of the TGFbeta superfamily of signaling molecules that direct differential cell fate decisions in a dose- and distance-dependent manner. During early embryonic development the Nodal/Activin pathway is responsible for the specification of mesoderm, endoderm, node, and mesendoderm. In contradiction to this drive towards cellular differentiation, the pathway also plays important roles in the maintenance of self-renewal and pluripotency in embryonic and epiblast stem cells. The molecular basis behind stem cell interpretation of Nodal/Activin signaling gradients and the undertaking of disparate cell fate decisions remains poorly understood. Here, we show that any perturbation of endogenous signaling levels in mouse embryonic stem cells leads to their exit from self-renewal towards divergent differentiation programs. Increasing Nodal signals above basal levels by direct stimulation with Activin promotes differentiation towards the mesendodermal lineages while repression of signaling with the specific Nodal/Activin receptor inhibitor SB431542 induces trophectodermal differentiation. To address how quantitative Nodal/Activin signals are translated qualitatively into distinct cell fates decisions, we performed chromatin immunoprecipitation of phospho-Smad2, the primary downstream transcriptional factor of the Nodal/Activin pathway, followed by massively parallel sequencing, and show that phospho-Smad2 binds to and regulates distinct subsets of target genes in a dose-dependent manner. Crucially, Nodal/Activin signaling directly controls the Oct4 master regulator of pluripotency by graded phospho-Smad2 binding in the promoter region. Hence stem cells interpret and carry out differential Nodal/Activin signaling instructions via a corresponding gradient of Smad2 phosphorylation that selectively titrates self-renewal against alternative differentiation programs by direct regulation of distinct target gene subsets and Oct4 expression. _PLoS Genetics

This finding has profound implications for experimental approaches to guided stem cell differentiation and / or stem cell self renewal. The ability to control multiple distinct sets of genes by titrating the dose of signaling molecules is likely to prove a very powerful tool for geneticists, stem cell researchers, and bio-developmental scientists.

In other longevity news, a team of scientists from multiple universities has helped elucidate how cryoprotectant molecules protect proteins from freezing. Future research should enlarge the scope of study to discover optimal cryoprotectants for cells, tissues, organs -- and eventually for entire organisms.

It is quite possible that different types and levels of cryoprotectant will prove optimal for different organs and tissues, so that in order to viably freeze and thaw an entire organism -- say, a human being -- a complex process of multiple simultaneous organ infusion with several cryoprotectants would be necessary.

Restoring Lost Memories: Hope for Long-Lived Brains?

2011-06-21T09:02:00.000-07:00

Our brains were not really meant to last for 80, 90, 100 years. Metabolic debris accumulates, DNA repair mechanisms break down, and function tends to degenerate at variable rates -- depending upon the individual's lifestyle and genetic complement. Now scientists at USC in Los Angeles are learning how to restore lost memories -- at least in rats.
Theodore Berger at the University of Southern California in Los Angeles, and colleagues, used electrodes implanted within the hippocampus to record patterns of brain activity while rats learned how to operate a sequence of levers to gain a reward.

Next, the team obliterated the memory of the task by injecting chemicals into the hippocampus that block the signalling between neurons needed to access long-term memories. When tested, the rats could no longer perform the task.

However, when the team used the electrodes to stimulate the brain with the same pattern of activity recorded when the rats first learned the task, their ability to operate the levers in the correct sequence was restored. The rats could temporarily access the original memory, even though the chemical blockade was still in place. When fed scrambled versions of the code, the rats could no longer perform the task.

Ultimately, the researchers hope to create implants that contain codes for 20 to 30 simple tasks, enabling people with brain damage to recover basic abilities that have been lost, such as speaking or dressing themselves.

Berger says that encoding these tasks will be very difficult. "These are very basic capabilities that we are investigating, and it has taken us a lot of effort to get this far," he says. _NewScientist
It is unlikely that the USC team actually encoded rat brain activity with any accuracy. Rather, the team was able to encode a sufficient "hint" so as to allow the rats to internally re-assemble or approximate their former memories. Even in a rat's brain, mental codes are more difficult than even the best scientists understand.

But it is a promising beginning that provides hope for the long-lived brains of the future.

Article Abstract from Jnl of Neural Engineering

More on Sleep, ATP, and Adenosine

2011-05-17T08:47:00.000-07:00

Sleep Phases and Progression

Levels of adenosine triphosphate (ATP), the energy currency of cells, in rats increased in four key brain regions normally active during wakefulness. Shown here is the energy surge measured in the frontal cortex, a brain region associated with higher-level thinking. Credit: Courtesy, with permission: Dworak et al. The Journal of Neuroscience 2010.
We spend roughly 1/3 of our lives in the state of sleep. Researchers are beginning to learn why we must do this, and are gleaning hints of possible technologies for bypassing at least part of the sleep imperative, and doing well on less sleep.
“For a long time, researchers have known that sleep deprivation results in increased levels of adenosine in the brain, and has this effect from fruit flies to mice to humans.” Abel said. “There is accumulating evidence that this adenosine is really the source of a number of the deficits and impact of sleep deprivation, including memory loss and attention deficits. One thing that underscores that evidence is that caffeine is a drug that blocks the effects of adenosine, so we sometimes refer to this as ‘the Starbucks experiment.’”

Abel’s research actually involved two parallel experiments on sleep-deprived mice, designed to test adenosine’s involvement in memory impairment in different ways.

One experiment involved genetically engineered mice. These mice were missing a gene involved in the production of glial transmitters, chemicals signals that originate from glia, the brain cells that support the function of neurons. Without these gliatransmitters, the engineered mice could not produce the adenosine the researchers believed might cause the cognitive effects associated sleep deprivation.

The other experiment involved a pharmacological approach. The researchers grafted a pump into the brains of mice that hadn’t been genetically engineered; the pump delivered a drug that blocked a particular adenosine receptor in the hippocampus. If the receptor was indeed involved in memory impairment, sleep-deprived mice would behave as if the additional adenosine in their brains was not there.

...To see whether these mice showed the effects of sleep deprivation, the researchers used an object recognition test. On the first day, mice were placed in a box with two objects and were allowed to explore them while being videotaped. That night, the researchers woke some of the mice halfway through their normal 12-hour sleep schedule.

On the second day, the mice were placed back in the box, where one of the two objects had been moved, and were once again videotaped as they explored to see how they reacted to the change.

“Mice would normally explore that moved object more than other objects, but, with sleep deprivation, they don’t,” Abel said. “They literally don’t know where things are around them.”

Both sets of treated mice explored the moved object as if they had received a full night’s sleep.

“These mice don’t realize they’re sleep-deprived,” Abel said.

Abel and his colleagues also examined the hippocampi of the mice, using electrical current to measure their synaptic plasticity, or how strong and resilient their memory-forming synapses were. The pharmacologically and genetically protected mice showed greater synaptic plasticity after being sleep deprived than the untreated group.

Combined, the two experiments cover both halves of the chemical pathway involved in sleep deprivation. The genetic engineering experiment shows where the adenosine comes from: glia’s release of adenosine triphosphate, or ATP, the chemical by which cells transfer energy to one another. And the pharmacological experiment shows where the adenosine goes: the A1 receptor in the hippocampus. _MedicalXpress

Abel's is a sophisticated experiment which covers a lot of possiblities. Combining the findings of this experiment with findings of previous experiments gives one a fuller picture of what is going on.
The brain has evolved certain activity in N2 sleep (sleep spindles) which apparently promotes the production of ATP from adenosine and phosphate groups. As ATP levels rise in N2 sleep, adenosine levels drop. So the sound sleeper receives both the benefits of higher ATP energy levels and the improved learning that results from lower hippocampal free adenosine levels.

More on sleep spindles (PDF)

Adenosine is a potent pharmacological agent, powerfully affecting heart rhythms. It also affects central nervous system activity in a largely inhibitory function, and also exhibits anti-inflammatory effects.

Adenosine and deep brain stimulation (DBS)

Why Do We Sleep? A brief look at stages of sleep, and possible benefits of sleep.

Cross posted to Al Fin, the Next Level

How could we manage on less sleep? The fastest route to achieving high-functioning sleep reduction would seem to involve electromagnetic brain stimulation or inhibition over particular brain areas at specific pulse frequencies. The aim would be to reduce adenosine levels -- and increase ATP levels -- in specific areas of the brain including the hippocampus.

Pharmacological methods for blocking adenosine's effect, such as used in the experimental mice in the study above, offer another possiblity -- although a time delay before approval for a new drug of at least 10 years is to be expected.

Genetic techniques for modifying adenosine production or re-uptake and ATP synthesis, are another likely approach -- eventually. At the present time, genetic (and epigenetic) treatment methods are far too primitive and clumsy to risk for such an objective as sleep reduction, for most people.

Other neuromolecules are likely involved in this puzzle, but at least this information offers a place to start.

Refurbishing the Brain, Making Humans Smarter and Happier

2011-04-19T09:59:00.000-07:00

“I think we’re getting closer to harnessing neurogenesis to improve cognition and mood in humans. This research may also help explain a bit of a mystery in the field, which we still don’t understand, regarding how the hippocampus can be involved with both cognition – which is its classic function – and in mood and anxiety-related functions. Perhaps the fact that pattern separation affects both the cognitive and mood domains is the beginning of an answer to that paradox,” said Dr. Hen. _StemCells
René Hen, PhD, professor of Neuroscience and Pharmacology, in the Departments of Neuroscience and Psychiatry at Columbia University and the New York State Psychiatric Institute, has discovered a possible escape hatch by which some members of society might escape the Idiocracy. It involves the use of chemicals called "BAX inhibitors." Particular members of that class of drugs have the potential to preserve newborn stem cells in the brain's hippocampus. And doing that could make all the difference in the course of a person's life success and happiness.
After boosting the number of neurons in the hippocampus, an area of the brain involved in memory and mood, the researchers tested the mice in both learning and mood-related tasks and looked for changes in behavior. The researchers found specific effects on learning tasks that involve a process called pattern separation, which is the ability to distinguish between similar places, events and experiences.

“This process is crucial for learning because it enables us to know whether something is familiar or novel,” said Dr. Hen. “If it is familiar, you move on to the next bit of information; if it’s novel, you want to be able to recognize that it’s new and give it meaning. These mice, with just more adult-born neurons, and no other changes in the brain, basically learn better in tasks where they have to discriminate between similar contexts.”

Earlier strategies for manipulating neurogenesis, according to the investigators, were broader and less specific. “In addition to stimulating neurogenesis, these earlier methods exerted many other effects on the brain. As a result, you never knew with these older manipulations what’s due to neurogenesis, or what’s due to the other effects that these manipulations cause, and, indeed, what we find is that when you stimulate just adult neurogenesis, you actually get a subtle effect. Unlike broader manipulations, it does not affect all forms of learning, it’s very specific to tasks that require pattern separation,” said Dr. Hen.

Pattern separation is not only important for learning; it may also be important for anxiety disorders, including post traumatic stress disorder (PTSD) and panic disorder. People with PTSD, say the researchers, have a more generalized fear response, so that when they are placed in a situation that reminds them of even one aspect of their trauma, they frequently have a full fear response.

...The researchers say that the genetic strategy used to stimulate neurogenesis in their experiments can be mimicked pharmacologically, potentially leading to the development of new drugs to reverse pattern separation deficits. One such class of drugs the investigators are currently testing – BAX inhibitors – works by blocking cell death.

“These drugs are basically doing the same thing that we did with our genetic manipulation-namely, increasing the survival of the young neurons which normally undergo a process of cell death that eliminates at least half of these neurons. Now instead of dying, the neurons will go on to survive,” said Dr. Sahay.

Some BAX inhibitors have been developed for stroke research, where the goal has also been to prevent neurons from dying. The Columbia researchers plan to begin testing the BAX inhibitors in mice shortly. And if they produce cognitive benefits, the testing will be extended to clinical trials to determine if there’s also a beneficial effect in humans. _StemCells
This is all related to the length of time required before antidepressants are able to bring about a full "antidepressive response." The full effect of modern antidepressants requires new stem cell production in the hippocampus -- but that takes time to achieve. Drugs capable of rapid and prolonged increases of hippocampal stem cells could conceivably keep anxiety and depression at bay, while improving a person's cognitive capacity.

No, this is not NZT. As mentioned here previously, a drug that could achieve the effect of the fictional NZT would have to stimulate changes in gene expression on multiple levels, and across a wide range of brain centers.

Smart drugs alone will not achieve the goal of smarter, better-rounded, and happier humans. Educational and environmental interventions would also be necessary, to blunt the Idiocratic brainwashing effect of modern media, modern academia, and modern popular culture, while allowing the brain to develop newer, more functional pathways.

Realistically, it will take 15 years at the earliest to see the early promise of this type of medication come to fulfillment. But a single ray of hope in the distance is worth a lot to a person immersed in the modern rush to Idiocracy.

More 5April2001: An example of rapid brain plasticity in human adults
The PNAS Abstract from the actual study

Previously published at Al Fin

As noted here before, improved neurogenesis in the hippocampus is associated with antidepressant and anti-anxiety behaviours in animal studies -- and probably in humans. It does no good to live longer with younger brains if we are unable to enjoy our added time and brainpower.

Inflammation Kills! Blocking the Inflammation After MI, CVA

2011-04-18T17:37:00.000-07:00

Blocking Complement
A person may survive a severe heart attack (MI) or stroke (CVA) only to succumb to the effects of devastating inflammation which tends to occur after blood supply is restored to tissue that was damaged from temporary loss of perfusion. An effective treatment for preventing such re-perfusion inflammation could save many hundreds of thousands of lives a year.
The lectin pathway is responsible for the potentially devastating inflammatory tissue response that can occur when any bodily tissue or organ is reconnected to blood supply following ischaemia – a temporary loss of that blood supply and the oxygen that it carries. This excessive inflammatory response is, in part, responsible for the morbidity and mortality associated with myocardial infarction (heart attack) and cerebrovascular accidents (CVAs or strokes). Moreover, the work succeeded in finding a way to neutralise this enzyme by raising a therapeutic antibody against it. A single antibody injection in animals has been shown to be sufficient to disrupt the molecular process that leads to tissue and organ destruction following ischaemic events, resulting in significantly less damage and markedly improved outcomes.

"This is a fascinating new achievement in the search for novel treatments to significantly reduce the tissue damage and impaired organ function that occur following ischaemia in widespread and serious conditions such as heart attacks and strokes," said Professor Schwaeble. "This new potential therapy was also shown in animals to significantly improve outcomes of transplant surgery and may be applicable to any surgical procedure where tissue viability is at risk due to temporary interruption of blood flow. _Eurekalert

Of course Professor Schwaeble is correct. Not only would such a treatment be a potential blockbuster drug for preventing complications from MI and CVA, but it would also be immensely useful for surgical procedures where blood supply is temporarily interrupted, or for treating cases of trauma where blood supply is interrupted by the trauma itself and/or by a lifesaving procedure such as a tourniquet or MAST suit used to prevent fatal exsanguination.
The University of Leicester led an international team whose research has been published today in the Early Online Edition of the Proceedings of the National Academy of Sciences (PNAS).

Professor Wilhelm Schwaeble of the Department of Infection, Immunity and Inflammation at the University of Leicester, initiated and co-ordinated research collaborations with King's College London, the Medical University of Fukushima, Japan and the State University of New York, to achieve the present breakthrough findings, which were published today in PNAS.

Professor Schwaeble and collaborators identified an enzyme, Mannan Binding Lectin-Associated Serine Protease-2 (MASP-2), that is found in blood and is a key component of the lectin pathway of complement activation, a component of the innate immune system. _Eurekalert

Total Brain Network Imaging Reveals Efficiency Loss w/ Ageing

2011-02-08T15:26:00.000-08:00

“While particular brain regions are important for specific functions, the capacity of information flow within and between regions is also crucial,” said study leader Scientia Professor Perminder Sachdev from UNSW’s School of Psychiatry.

“We all know what happens when road or phone networks get clogged or interrupted. It’s much the same in the brain.

“With age, the brain network deteriorates and this leads to slowing of the speed of information processing, which has the potential to impact on other cognitive functions.” _Science Alert

University of New South Wales researchers have utilised advanced diffusion tensor imaging (PDF research article) along with powerful computational tools to assess the efficiency of the total brain network of white matter, and watched overall brain processing speeds as they slow due to ageing.
The research team, led by Scientia Professor Perminder Sachdev from the UNSW School of Psychiatry, has mapped the network of fibres or ‘white matter’ for the first time, allowing them to examine the strength of connections between different cortical regions, or ‘grey matter’, which are responsible for specific functions. In the past, most research has focused on the more complicated grey matter without looking at how information flows between separate regions.

A new type of magnetic resonance imaging (MRI) called diffusion tensor imaging (DTI) combined with powerful computers allowed the team to create the map and see the whole network in great detail.

“Using a mathematical theory you can see how strongly the different regions are connected to each other,” Professor Sachdev said. “You can basically look at the efficiency of the network and with ageing, we can see a reduction in the efficiency of these networks.”

“What we wanted to see is how this relates to cognitive function, and we found that the best relationship was with processing speed, which makes sense because we’re talking about strength of information connections.”

Other areas strongly affected by the efficiency of neural networks were executive functions that manage other brain processes and the ability to navigate in space, known as visuospatial function.

Sachdev said the findings could help to some extent with dementia research, by offering another way of looking at the condition, but had already helped explain what happens in the brain when physical reaction time slows down in older people.

“It’s not that they can’t do the task, it just takes longer, and we have shown that this is related to structural changes in the brain, in terms of its neural networks.”

“The next step is looking at what determines the efficiency of these networks. We want to see if they are flexible or plastic, and whether maybe we can intervene.”

...The results of the study, which was based on a sample of 342 healthy people aged between 72 and 92, have been published in the January edition of the Journal of Neuroscience. _AustralianAgeingAgenda

Here is more from science alert Australia:

In the study, the researchers performed magnetic resonance imaging (MRI) scans on 342 healthy individuals aged 72 to 92, using a new imaging technique called diffusion tensor imaging (DTI).

Using a mathematical technique called graph theory, they plotted and measured the properties of the neural connectivity they observed.

“We found that the efficiency of the whole brain network of cortical fibre connections had an influence on processing speed, visuospatial function – the ability to navigate in space – and executive function,” said study first author Dr Wei Wen.

“In particular greater processing speed was significantly correlated with better connectivity of nearly all the cortical regions of the brain.”

Professor Sachdev said the findings help explain how cognitive functions are organised in the brain, and the more highly distributed nature of some functions over others. _Science Alert

It is important to stress the difference between speed of nerve transmission and speed of information processing for the brain. The two are related, and both are measurable (or calculable) using the DTI computational techniques, but information processing is a much higher order process than mere nerve conduction velocities. Knowing processing speeds -- particularly being able to compare whole brain processing and subsystem processing speeds and efficiencies -- provides more information.

Diffusion Tensor Imaging (DTI) can be used to assess several aspects of brain functioning, including general intelligence and executive function. It can also be used to assess multiple types of brain pathology, including schizophrenia.

Better brain imaging techniques provide clinicians and researchers with better information with which to form theories and plan therapies. As brain ageing comes to be seen more as a reversible pathology, more advanced diagnostic tools and therapeutic methods will be made available more widely.

Are We Closer to Viable Long-Term Freezing for Organs and People?

2011-01-25T11:24:00.000-08:00

Once we are able to viably freeze and thaw living organs and whole animals, without damage or injury, we will be able to plan for the targeted freezing and thawing of living humans for purposes of extended survival.

A technology that has come from the frozen sushi industry in Japan is being studied for possible application to living animals and human organs such as hearts, livers, lungs, and kidneys.
A technology used to freeze sushi is solving a dilemma for organ storage. By borrowing tech used to preserve high-end food delicacies, a Hiroshima University research group proved it possible to safely freeze whole teeth and their delicate attaching tissues. As long as the freezer stays cold, the folks at Hiroshima U. think your teeth could be stored for 40 years, no problem.

But the sushi-storage system isn’t a one trick pony: internal organs could be next thanks to the magic of supercooling. In typical cryo-storage, fast freezing of organs requires poisonous levels of anti-freeze, and let’s face it, no one wants a poisoned kidney transplanted into their body. But slower freezing causes cell popping ice crystals to form.

So, what do you do to prevent ice crystals during slow freezing? Use magnets. ABI is the Japanese company producing the freezer system. ABI’s “Cells Alive System” (CAS) vibrates water with magnetic fields, preventing freezing, even at supercool temperatures of -10 degrees Celsius (According to the Patent.) When the field is turned off, the water in the food instantly freezes. No time for ice growth means no Freddy Krueger action on frozen organs.

...The transition of this tech from food to longevity science is slowly evolving, but the steps forward are real. You can, right now, pay to store your teeth. Hiroshima University tested the cooling technology for teeth, and uses ABI CAS freezer tech at The Teeth Bank, the world’s first commercial tooth bank. Dr. Toshitsugu Kawata, a Hiroshima University professor who has done extensive research at the Teeth Bank, helped prove that CAS is a viable technology to preserve teeth. Spare teeth used to be worthless medical waste. Now, removed wisdom teeth aren’t garbage, they can be frozen and re-implanted at any point during your life.

...The founder of the ABI Corporation and its CAS freezer, Norio Owada (known internationally as “Mr. Freeze,”) is actively pursuing medical advances. There’s a hodgepodge of reports out there about what’s being done. According to various sources, Mr. Freeze is collaborating with 40 researchers to translate their work with teeth and sushi to hearts, nerves, and other organs. Transplant medicine could benefit tremendously. With further research, this technology could supercool, or even freeze internal organs, putting an end to the dangerously brief time frame for organ transplants. In a 2008 Forbes article, Mr. Freeze speculated on where his technology may lead. “If you could preserve a heart for three days, you could fly it anywhere.” On the late-night Japanese TV show, World Business Satellite, there was discussion of research towards using ABI’s CAS freezers to store ovaries during cancer treatment, allowing women to keep their fertility. On the ABI company webpage, photos of a rat heart transplant and undamaged cell walls of frozen wasabi are a reminder of the unusual coupling of frozen food and medicine. _SingularityHub_via_NextBigFuture
One further step is needed: a vitrification agent which can be added to the supercooled organs which would allow the electromagnetic field to be turned off without the risk of freezing. One step at a time.

The Virtues of Experience

2011-01-24T08:25:00.000-08:00

Wikipedia
The human brain learns a lot, over time. Experience shapes the brain, determining how it will work, and which parts of the brain will be active in different circumstances. Recent Japanese brain research has determined that expert players in the Japanese chess game "Shogi" use a different part of their brain (the caudate nucleus) to play, than do amateurs of the game. The caudate nucleus is the curved purple structure in the image above.
Neuroscientists at the RIKEN Brain Science Institute in Wako, Japan, studied a group of professional and amateur shogi players. Shogi is the Japanese version of chess. With the use of real-time brain scans, the researchers discovered that the pros activated different parts of their brains than the amateurs did while studying game patterns and contemplating their next moves.

The findings were published in the Jan. 21 issue of Science.

Senior study author Keiji Tanaka, deputy director of the institute and head of the Cognitive Brain Mapping Laboratory, said the experts' unique brain circuitry enabled them to have "superior intuitive problem-solving capabilities."

Professional shogi players, who have practiced three or four hours a day for several years, "repeatedly note that the best next move comes to their mind 'intuitively,'" the authors wrote. "Being 'intuitive' indicates that the idea for a move is generated quickly and automatically without conscious search, and the process is mostly implicit."

...r brain difference occurred when the players were forced to quickly pick their next best move. The professionals' brain scans revealed activity in a portion of the basal ganglion known as the caudate nucleus, while the amateurs' scans did not.

The researchers suggest that a unique circuit between these two regions of the brain is what enables professional players to expertly recognize board game patterns and quickly choose their optimal next move.

"There was no volume difference of the caudate nucleus between professional and amateur players," said Tanaka. This suggests that "the caudate nucleus is used for other purposes in ordinary people [but] the experts have developed a unique way to use the system." _BW_via_ImpactLab
The caudate nucleus has been implicated in the development of automaticity of several types -- which places the caudate in a central, pivotal position for humans living in modern societies.

First, the caudate appears to be involved in the acquired automaticity of motor skills. This is not such a big surprise to brain researchers. But the caudate also seems to be involved in the automaticity of emotional processing, the automaticity of perceptual categorisation (PDF), automaticity of rule-based categorisation, and in switching between two languages in bilingual individuals. There are almost certainly more caudate functions to come.

Sure, there is overlap between the different caudate functions, but the brain -- and its many modular parts -- is nothing if not multi-functional. A Swiss Army knife of cognitive and emotional tools that modifies itself over a person's lifetime, adapting to the individual's experience.

That is why it is so important to the individual that the brains many potential functions be developed before their developmental windows close. And why it is so important to society that the brains of its members are well developed and long-lived.

We cannot afford to waste all of that hard-earned knowledge, experience, and savvy by dying too young. 500 year lifespans should be seen as a minimum timespan for skills acquisition and for passing these skills along to future generations.

DNA for Healthy Aging, and Rebuilding the Brain After Stroke

2010-11-04T11:35:00.000-07:00

We will look at two studies that relate to the quest for longer, healthier, more productive and fulfilling lives. First, researchers at the University of Miami looked at an Amish population and discovered that a certain genetic pattern in the mitochondria seems to allow for a much healthier lifespan into the 80s.
On Friday they will present a paper showing that 15 percent of healthy Amish octogenarians have "haplogroup X," a genetic pattern within the mitochondria, which are the regions of cells that generate energy and help guard against deterioration. Haplogroup X is generally found in only 2 percent of Europeans, from whom the Amish descended. In the University of Miami study, only 3 percent of the control group—Amish people who had made it to 80 but suffered from significant disease or disability—had the genetic variant. The paper will be featured during a session at the American Society of Human Genetics' annual meeting in Washington, D.C.

Researchers who study aging have long suspected that mitochondria play a role in aging. Mitochondria are responsible for processing metabolized food particles into adenosine triphosphate, which fuels vital cellular processes. They're also involved in cell growth and differentiation. But the ability of mitochondria to function properly seems to decline with age.

Understanding the reason for that decline—and the genes that might control it—has been challenging. Mitochondria have their own DNA, which is passed down from the mother only. This unique chromosome has variations, called haplogroups. Nine such haplogroups have been well characterized in people of European descent, Scott says. But only haplogroup X was found to be prevalent among healthy aged people in the University of Miami study. _TechnologyReview

The second study, from UCLA researchers, looks at the ability of the brain to re-build following stroke -- or brain infarct. The team appears to have discovered a drug target with significant promise, which may lead to drugs that help the brain to re-build itself following destructive lesions.
A stroke is usually caused by a clot that blocks blood flow to an area of the brain. Tissue in that part of the brain dies from lack of oxygen unless the clot is detected immediately and is either dissolved or removed. The dead tissue cannot be revived, but often the brain can be trained to redirect nerve impulses via still-living nearby neurons. But such training is difficult, can require months to years of arduous rehab, and is often not sufficient to overcome complex disability.

The new research, by neurologist S. Thomas Carmichael and his colleagues at the University of California at Los Angeles, shows that neurons in the areas of the brain closest to the site of a stroke are impaired after it occurs. The reason for that is a buildup of an inhibitory signaling molecule called GABA that prevents the neurons from firing. When those nerves are inhibited, it's harder for the brain to recruit them into its rerouted circuits.

In studies in mice, the researchers discovered that blocking a particular piece of the GABA signaling system with an existing drug allowed the nerves to reactivate, reversing the repressed excitability, allowing them to more easily respond to other neurons, and encouraging and enhancing early recovery after a stroke by as much as 50 percent. "At face value, it's a new pharmacological target for repair and recovery in stroke," Carmichael says.

...Carmichael and his colleagues identified the piece of the GABA signaling cascade that goes awry in the area of the brain adjacent to the stroke: reduced levels of a transporter responsible for moving the inhibitory molecule out of the vicinity. Without that transporter, GABA is allowed to reach such high levels that the nearby neurons are prevented from firing.

In studies in mice, the researchers induced a stroke in the motor cortex, the movement center of the brain, and then gave them a drug that specifically reverses the post-stroke GABA uptake. The drug is not approved for use in people—it was an experimental molecule produced during the drug industry's search for memory enhancers. But just the fact that it works in mice means that stroke researchers have a new line of evidence to pursue.

"It's significant, because they're identifying a molecular mechanism that is keeping stroke survivors from recovering. And as a result, [Carmichael is] identifying targets for molecular manipulation," says Theresa Jones, a neurobiologist at the University of Texas at Austin. "Now we have potential to find drugs that aim at that target."

The scientists found that, as with other types of stroke treatments, timing was critical. During the first few days after a stroke, a brain injury is still stabilizing; prior studies have shown that any physical rehabilitation attempted during this period can aggravate the brain and actually make the damage worse. The same proved true for the drug.

But when the mice were given the drug three days later, it improved their recovery of movement by 40 to 50 percent. This implies that while the post-stroke inhibition of neurons in these areas may help with immediate recovery, but it is a harmful adaptation when it persists for weeks or months or even years after the initial injury. _TechnologyReview
Stroke is one of the major causes of death and disability in the developed world. A viable treatment for stroke rehabilitation would be a significant medical development.

Reversing Age Related Memory Loss

2010-10-18T05:25:00.000-07:00

Researchers estimate that roughly 20 to 30 percent of people age 75 and older have elevated glucocorticoid levels (more precise figures aren't available). Most affected is so-called declarative memory, the ability to learn new facts and remember, for example, lists. People who suffer age-related memory loss are at higher risk for developing Alzheimer's and other forms of dementia, though the condition is not itself considered a form of dementia. _TechnologyReview
A research team at the University of Edinburgh have developed a new compound that appears to prevent and reverse age-related memory decline in mice. Their approach utilises a "gene knockout" approach against an amplifier of glucocorticoid effect present in brain cells.
"What's most surprising is that even short-term inhibition was able to reverse memory loss in old mice," says Jonathan Seckl, a professor of molecular medicine who was involved in the research. "I don't think people had realized this was so reversible. It takes [the animals] back to being relatively young."

The researchers hope to develop equivalent human therapies and are now more extensively studying the safety of a closely related compound in animals. They aim to begin human testing within a year.

Scientists have long known that glucocorticoids--a class of steroid hormones that mediate our response to stressful situations--play a role in age-related memory decline. Although short-term exposure to glucocorticoids enhances the formation of memories during stressful situations, chronically high levels of the hormones are linked to greater memory loss with age, both in humans and animals. The exact mechanism underlying this link is unclear, but researchers theorize that excess exposure to the hormones makes parts of the brain more vulnerable to damage.

Seckl and his collaborators focused on an enzyme called 11β-hydroxysteroid dehydrogenase type 1 (11 β-HSD1). This enzyme generates an active version of the key glucocorticoid hormone within brain cells and some other tissues, providing a target for fine-tuning the system without blocking the overall stress response. Tinkering with the enzyme seems to have little effect on blood levels of glucocorticoids, which are produced in the adrenal glands. Instead, "this enzyme acts as an intracellular amplifier of glucocorticoids," says Seckl. "If you take out the amplifier, you still have stress hormones, but they shout less loudly and cause less wear and tear."

The Edinburgh team showed that knocking out either one or both copies of the gene for this enzyme in mice preserved the animals' memory into old age. To determine whether blocking the enzyme could improve memory in already aged animals, researchers then developed a compound designed to cross into the brain and inhibit the enzyme. Just 10 days of treatment in two-year-old mice--the maximum lifespan for a typical lab mouse--was enough to improve the animals' performance on a test of spatial memory. The treatment "returned mice to the equivalent of when they were young and fully functioning," says Brian Walker, another researcher involved in the study. "It's important to emphasize that we are trying to target the pathology--the role that glucocorticoids play in age-related memory decline--not just globally improving memory." The research was published last week in the Journal of Neuroscience. _TechnologyReview

Brian Wang looks at another approach to augmenting human brainpower

Also published at Al Fin

Open Source Biotechnology: The Wonder and the Terror

2010-09-03T16:06:00.000-07:00

As recently as a decade ago, the tools and techniques for such fiddling were confined to a handful of laboratories like those at leading research universities. Today, do-it-yourself biology clubs have sprung up where part-timers share tips on how to build high-speed centrifuges, isolate genetic material, and the like. The movement has been aided by gear that can turn a backyard shed into a microbiology lab. _WSJ

With the emergence of open-source biohacking, a number of scientists and authorities are starting to worry about the possibility that a biohacker will create some type of super-microbe which could cause a significant disease outbreak. Here you can find a zipped download introduction to biohacking.
The new fear, though, is that scientific advances that enable amateur scientists to carry out once-exotic experiments, such as DNA cloning, could be put to criminal use. Many well-known figures are sounding the alarm over the revolution in biological science, which amounts to a proliferation of know-how—if not the actual pathogens.

"Certain areas of biotechnology are getting more accessible to people with malign intent," said Jonathan Tucker, an expert on biological and chemical weapons at the James Martin Center for Nonproliferation Studies.

Geneticist Craig Venter said last month at the first meeting of a presidential commission on bioethics, "If students can order any [genetic sequences] online, somebody could try to make the Ebola virus."

Mr. Venter is a pioneer in the field whose creation of a synthetic organism this spring helped push the debate about the risks and rewards of bioscience from scientific journals to the corridors of power in Washington. "We are limited more by our imagination now than any technological limitations," Mr. Venter said.

Scientists have the ability to manipulate genetic material more quickly and more cheaply all the time. Just as "Moore's Law" describes the accelerating pace of advances in computer science, advances in biology are becoming more potent and accessible every year, experts note. _WSJ
Of all the things likely to escape from garage biohacking outposts, none are likely to bring about the end of the human species. Some of them may even be beneficial for health and long life.

Just as some of the fastest developments in personal computing emerged from basements and garages, so is it possible for home-based biohackers to make important contributions to bioscience and biomedicine. Curiosity drives most small scale hacking of all kinds -- the desire to understand how things work.

For humans who are interested in going beyond the ordinary in terms of lifespan, intelligence, sleep requirements, strength, speed, etc. the answers may well arise from small scale independent labs -- given how over-regulated and over-restricted all aspects of government sanctioned biomedicine are becoming in western countries.

Is there a danger? Yes, there is always a danger, and all of us should stay alert for persons who seem to be several cards short of a full deck. But that shouldn't stop us from pushing the limits.

Regenerative Medicine Advances

2010-08-23T08:15:00.001-07:00

The promise of regenerative medicine involves a future where replacement organs and tissues can be re-grown in a lab from a person's own cells, then transplanted into the person as brand-new, fully functioning replacement tissue. Replacement lung tissue, replacement heart tissue, replacement ligaments and tendons, replacement skin, kidneys, muscle, intestine, bladders, and on and on. But first, scientists have to find a good way to grow millions and billions of healthy stem cells from a person's own cells, and keep them alive long enough to turn them into the proper tissue, and grow them on a proper scaffold into the proper replacement organs.

Investigators from the Massachusetts Institute of Technology (MIT) recently developed a new type of support structure for stem cells, which allows them to remain alive for weeks without using any foreign genetic material.

Generally, substrates for growing stem cells contain animal cells or tissue, but these can easily contaminate the samples themselves, which means that they can lose some of their capabilities.

This is an especially serious consequence for induced pluripotent stem cells, which are biological units that can transform into any type of tissue in the human body.

Only environmental conditions dictate whether they will turn into nerve cells, or into pancreatic tissue.

Due to this amazing differentiation ability they have, these cells hold great promise for treating a number of disorders, such as for example Parkinson's, multiple sclerosis and spinal cord injuries.

But, in order to make the best of them, researchers need to be able to grow them in sufficiently large quantities, and this is proving to be extremely difficult due to the lack of proper substrates.

One of the main issues in this field of research is the fact that human stem cells are now grown with the aid of cells or proteins derived from mice embryos. If these foreign chemicals would interact with the human body, they would definitely cause an allergic reaction.

Thanks to the MIT collaborations, which includes biologists, materials engineers and chemists, scientists now have a synthetic surface that features no material from mice or other animals.

The data the team recorded of the new surfaces show that they promote and sustain “all-natural” stem cell growth and reproduction for at least three months. Longer periods are also possible, the group says.

Another impressive feat the MIT experts achieved with their new material is the fact that it allows for researchers to separate colonies of identical cells from each other. The surface allows single cells to form colonies of cells of that type with considerable ease.

Details of the new investigation appear in the August 22 issue of the esteemed scientific publication Nature Materials, e! Science News reports. _Softpedia
Another report from ScienceDaily

“For therapeutics, you need millions and millions of cells. If we can make it easier for the cells to divide and grow, that will really help to get the number of cells you need to do all of the disease studies that people are excited about,' says MIT postdoctoral associate Krishanu Saha, one of the co-first authors of the paper.

The work was led by MIT professors Robert Langer, Rudolf Jaenisch and Daniel G. Anderson, in collaboration with Saha and postdoctoral researcher Ying Mei. _Softpedia

This report from Brian Wang on Swiss stem cell research, suggests that mature tissue-derived stem cells can be programmed across germ layer boundaries. This finding hints at the possibility of creating virtually any type of cell or tissue from any other type of tissue -- including easily sampled tissues such as skin or blood.

Cross-posted at Al Fin

The Aging Brain: Endangered by Runaway Development?

2010-07-20T08:12:00.000-07:00

Mehmet Somel, a Turkish researcher doing post-doctoral work in Shanghai, has uncovered some fascinating genetic evidence suggesting that inappropriate-for-age gene regulation may be endangering aging brains:Researchers have now identified a gene regulatory link between changes in the young and aging brain.

The brain undergoes rapid growth and development in the early years of life and then degenerates as we progress into old age, yet little is known about the biological processes that distinguish brain development and aging.

Underlying brain development is the complex and coordinated process of gene regulation.

"In development, many genes are turned on and off by regulators, such as transcription factors and microRNAs. The question is, do all of these regulatory processes cease once adulthood is reached, or are they still active in aging?" said Mehmet Somel, postdoctoral researcher at the Shanghai Institutes for Biological Sciences.

The researchers investigated messenger RNA (mRNA), microRNA, and protein expression changes in the prefrontal cortex of humans and rhesus macaque monkeys over the life span of each species.

The group found that distinct patterns of gene regulation in the prefrontal cortex do not stop at maturity, instead persisting into old age, a phenomenon that was observed for many different functional processes.

...The researchers showed that this process begins as early as three to four years of age, suggesting that these changes may be normal developmental regulation that continues long into old age.

While this regulation is likely to be beneficial during development, at old age continuation of the gene regulation, or "runaway" development, might be detrimental.

Interestingly, they found the runaway neuronal development to be conserved in macaques, but it occurs an accelerated rate.

Because the regulatory processes progress much faster, the authors suggest that this could be a significant contributor toward limiting the life span of macaques to only about one-third that of humans. _SiFy
Researchers will now need to determine whether a more "age-appropriate" pattern of gene regulation would allow for persistence of normal brain functioning further into old age.

It is known that DNA repair loses efficiency with increasing age. If inappropriate genes are consistently "over-clocked" at levels more appropriate to younger ages, the compounding of genetic errors due to inefficient DNA repair would occur more quickly and take on more significance.

This is a fascinating area of study, well worth following.

Can Delaying Puberty & Extending Childhood Increase Lifespan?

2010-07-15T16:13:00.000-07:00

Puberty seems to be arriving at earlier ages for both boys and girls. There are many reasons why puberty onset is earlier now, but most of these reasons are still unclear. The problems that arise from premature puberty include violence, higher risks of cancer and diabetes, increased behavioural problems (drugs, alcohol, delinquency etc), isolation from peer groups -- even a change in growth rates for the children of girls with premature onset of puberty.

ImageSource
...children who go into early puberty are prematurely sexualised and too immature to deal with the implications. They are more vulnerable to sexual abuse, inappropriate sexual behaviour, sexually transmitted diseases and teenage pregnancy. “It means that children develop sexually much earlier,” Stanhope says. “They are physically ready for sexual reproduction but mentally completely unready.”

Studies have shown that adolescents who go through puberty earlier are involved in more risk-taking behaviour, such as taking drugs, binge drinking and breaking the law. A premature increase in testosterone can lead to aggression in boys who lack the maturity to control impulses. “We all realise that testosterone is a very difficult hormone to learn to live with,” Stanhope says, tapping a pencil vigorously on his pockmarked table, “and if you get a rise in testosterone outside the normal physiological age, then it’s even more of a problem.”

Research published this year in the Australian and New Zealand Journal of Criminology also found increased aggression in girls who reached puberty early. In Britain the uncomfortable reality that children are becoming sexually mature earlier has been overlooked in the recent debate about the over-sexualisation of children. Instead of simply focusing on cynical manufacturers producing padded bras for seven-year-olds, perhaps we should also consider how to respond to the new reality that some girls are now growing breasts at this age.

Stanhope also points out that for women there may be long-term health problems, because early puberty increases exposure to oestrogen. According to Cancer Research UK, a girl who has her first period a year later than her contemporaries has 5% less risk of developing breast cancer in later life. “There may be an important link with breast and ovarian cancer,” Stanhope says. “The earlier a girl has her period, the longer her exposure to oestrogen and this may well have very important sequelae for oestrogen-dependent tumours. This increases her risk of breast cancer, ovarian cancer and of developing cardiovascular problems.”

Girls who reach puberty early are also more likely to develop type 2 diabetes. A 37-year-long study of 61,000 Norwegian women showed that women who got their first period at ten or 11 had a 10% higher mortality rate than those who got their period four years later. _PubertyBlues

Scientists are beginning to home in on the physiological initiators of puberty, and have found a way to delay puberty in mice. By "knocking out" a specific gene, IGF-1R, researchers have both delayed puberty and maintained normal reproductive function after puberty in these knockout mice.
Pubertal onset, initiated by pulsatile gonadotropin-releasing hormone (GnRH), only occurs in a favorable, anabolic hormonal milieu. Anabolic factors that may signal nutritional status to the hypothalamus include the growth factors insulin and IGF-1. It is unclear which hypothalamic neuronal subpopulation these factors affect to ultimately regulate GnRH neuron function in puberty and reproduction. We examined the direct role of the GnRH neuron in growth factor regulation of reproduction using the Cre/lox system. Mice with the IR or IGF-1R deleted specifically in GnRH neurons were generated. Male and female mice with the IR deleted in GnRH neurons displayed normal pubertal timing and fertility, but male and female mice with the IGF-1R deleted in GnRH neurons experienced delayed pubertal development with normal fertility. With IGF-1 administration, puberty was advanced in control females, but not in females with the IGF-1R deleted in GnRH neurons, in control males, or in knockout males. These mice exhibited developmental differences in GnRH neuronal morphology but normal number and distribution of neurons. These studies define the role of IGF-1R signaling in the coordination of somatic development with reproductive maturation and provide insight into the mechanisms regulating pubertal timing in anabolic states. _JCI
Scientists will find additional triggers for pubertal onset besides insulin and IGF-1, and some of those factors may provide a more benign approach to the delaying of puberty.

Paradoxically, IGF-1 is vital for normal development of mice, but knocking out IGF-1 receptors in certain flies and worms can increase lifespan. That paradox is still being studied.

So -- how long should puberty be delayed, if at all? If childhood could be extended for several more years without impairing the ability of the child to learn and mature psychologically, would the potential health and societal benefits be worth the postponement of sexual development of the child?

What if aging itself were to be postponed along with puberty? If total lifespan were extended by the number of extra years a person spent in childhood, would that be beneficial to society or not? What if a person could live an extra 20, 30, or 50 years -- but had to spend those extra years as a pre-pubertal child. Would it be worth it?

Those who see increased longevity as a sure path to overpopulation collapse of Earth's ecosystem, would insist upon some form of sterilisation for those who opt for longevity. In some countries, laws of that type -- mandating permanent sterilisation for anyone undergoing longevity treatments -- should be expected.

Extended pre-puberty is a form of time-limited and (probably) reversible sterilisation, so any longevity approach that also delayed puberty significantly, should not raise the hackles of those suffering from overpopulation anxiety too much. But there are likely to be a large number of objections to such treatments, all the same.

Modern societies appear to see children in a schizoid manner. Fewer children are born, so the one or two children a family does have, are cherished and pampered. On the other hand, children are seen as a hindrance to a hedonic lifestyle, an exorbitant expense and often a great bother. Overall, most children do not seem to be raised or educated very well in modern societies, judging by observable results.

While childhood is not prolonged in modern societies, an incompetent adolescence is certainly prolonged -- in many cases indefinitely. Given the choice between a prolonged childhood leading into an accelerated but prepared-for adolescence, and the current state of lifelong incompetent adolescence commonly seen in the affluent world, most Al Fin mental health professionals would choose the prolonged childhood combined with a prepared-for adolescence that leads into a responsible and competent adulthood.

Previously published at Al Fin

A New Class of Molecules that May Cure Alzheimer's

2010-07-09T06:47:00.001-07:00

New nerve cells are constantly born in the hippocampus, but even in the normal adult brain, most of these newborn neurons die before they become functional.

And they fare much worse in the hippocampus of Alzheimer's patients.

Physical activity, an active social life and other intellectually and emotionally enriching experiences promote the birth and maturation of new neurons.

The scientists wanted to find compounds that can protect newborn neurons from dying.

P7C3 was selected from among about 1,000 compounds tested on mice.

The compound was found to help the survival of neurons in adult mice, which were genetically engineered to lack a gene that is crucial for the survival of newborn nerve cells. _IndiaToday

ScienceDaily
University of Texas Southwestern have reported in Cell the discovery of a molecule -- P7C3 -- that has the ability to protect brain cells, and trigger the production of new neurons. The scientists believe that new compounds in the same class as P7C3 may hold the key to slowing or temporarily reversing the progress of Alzheimer's Disease and other neurodegenerative conditions.
In a new study published today in the journal Cell, researchers screened 1000 molecules in mice to see which ones enhanced production of new neurons in a brain area involved in learning and memory. This region, known as the hippocampus, is one of two spots known to birth new neurons in the adult mammalian brain. It takes 2 to 4 weeks for the cells to migrate to the appropriate location and integrate into the existing neural circuitry, and many of them die along the way.

The researchers found that one compound, dubbed P7C3, protected these newborn neurons from dying. When given to mice genetically engineered to have very little new nerve cell growth, the compound seemed to repair the abnormal hippocampus. It could also increase birth and survival of new neurons in older rats, according to a press release from UT Southwestern Medical Center. The animals also had improved memory: they could better remember the location of a platform submerged in water, a standard test of learning and memory in rodents.

...
According to a release from the journal Cell, where the paper was published;

Two other drugs (Dimebon and Serono compounds) - both of which bear structural similarities to P7C3 -also encourage the growth of new neurons. It's tempting to think that all three compounds work in the same way.
In fact, Dimebon first came to the attention of researchers based on anecdotal reports by Russian physicians that the drug may ameliorate the symptoms of age-related cognitive decline. Unfortunately, unpublished reports from a phase 3 clinical trial have since failed to provide evidence that the drug could stave off the memory loss that comes with Alzheimer's disease.

In light of the new findings, it may be worth another look. "The speculative idea that these chemicals share a common mode of action will only be rigorously tested upon identification of their molecular target(s)."
_TechnologyReview

Pieper, McKnight and colleagues tested more than 1000 small molecules in living mice. One of the compounds, designated P7C3, corrected deficits in the brains of adult mice engineered to lack a gene required for the survival of newborn neurons in the hippocampus. Giving P7C3 to the mice reduced programmed death of newborn cells -- normalizing stunted growth of branch-like neuronal extensions and thickening an abnormally thin layer of cells by 40 percent. Among clues to the mechanism by which P7C3 works, the researchers discovered that it protects the integrity of machinery for maintaining a cell's energy level.
To find out if P7C3 could similarly stem aging-associated neuronal death and cognitive decline, the researchers gave the compound to aged rats. Rodents treated with P7C3 for two months significantly outperformed their placebo-treated peers on a water maze task, a standard assay of hippocampus-dependent learning. This was traced to a threefold higher-than-normal level of newborn neurons in the dentate gyrus of the treated animals. Rats were used instead of mice for this phase of the study because the genetically engineered mice could not swim.
Prolonged treatment of aged rats with P7C3 also enhanced the birth of new neurons. "Aged rats normally show a decline in neurogenesis associated with an inability to form new memories and learn tasks," Pieper explained.

In their study, rats treated with P7C3 each day showed evidence of an increase in the formation of newborn neurons and significant improvements in their ability to swim to the location of a missing platform, a standardized test of learning and memory in rats.

The researchers pinpointed a derivative of P7C3, called A20, which is even more protective than the parent compound. They also produced evidence suggesting that two other neuroprotective compounds eyed as possible Alzheimer's cures may work through the same mechanism as P7C3. The A20 derivative proved 300 times more potent than one of these compounds currently in clinical trials for Alzheimer's disease. This suggested that even more potent neuroprotective agents could potentially be discovered using the same methods. Following up on these leads, the researchers are now searching for the molecular target of P7C3 -- key to discovering the underlying neuroprotective mechanism. _ScienceDaily
The study was two-tiered: First the scientists screened over a thousand small molecules in knockout mice, to find the one that provided the best protection for new hippocampal neurons. Then they tested the compound in senescent rats, looking for both behavioural improvements and better survival of new hippocampal neurons. They were successful on all counts.

H/T Brian Wang of NextBigFuture

Cross-posted to Al Fin

Bortezomib Prunes Inflammatory T Cells: Hope for Inflammatory Diseases that Make the Young Old and Make the Old Want to Die

2010-06-30T18:22:00.000-07:00

Inflammatory diseases such as arthritis, inflammatory bowel disease, multiple sclerosis, lupus, and many more, can strike at any time. Such diseases can create such suffering and disability that they make young people old very quickly, and can make old people wish they were dead.

A fairly new drug in the proteasome inhibitor class, Bortezomib, is used to treat a cancer of the bone marrow cells, multiple myeloma. But now, scientists have discovered a new use for Bortezomib: killing off active and proliferating T cells that cause so much damage in inflammatory diseases -- while leaving the resting T cells alone.
Those looking for a new treatment for a range of inflammatory diseases like arthritis, multiple sclerosis, inflammatory bowel disease, and lupus may need to look no further than a drug already available for treating cancer. In a research report published in the July 2010 print issue of the Journal of Leukocyte Biology (http://www.jleukbio.org), Japanese scientists use mice to show that bortezomib, currently used to treat cancers that affect white blood cells, induces cell death only in harmful (active and proliferating) T cells, leaving the rest unharmed. If the results prove true in humans, it offers hope that this drugs or others similar to it might be used to treat inflammatory diseases without the side effects of current drugs that affect all T cells equally.

"Unfortunately, there are a lot of people who are suffering from autoimmune and inflammatory disease," said Koichi Yanaba, M.D., Ph.D., a scientist from the Department of Dermatology at Nagasaki University Graduate School of Biomedical Sciences who was involved in the research. "We believe that this new-type remedy for autoimmune and inflammatory disease could successfully treat them in the near future."

To make this discovery, scientists used two groups of mice—the first treated with bortezomib and the second with saline. Researchers induced contact hypersensitivity reaction with oxazolone, a chemical allergen used for immunological experiments and found that bortezomib significantly inhibited the contact hypersensitivity responses. Results strongly suggest that bortezomib treatment enhanced T cell death by inhibiting NF-kappa B activation, which plays a key role in regulating the immune response to infection. This in turn led to the suppression of inflammatory responses in immune cells by reducing interferon-gamma production. _Eurekalert

Inflammation complicates many diseases of old age, including Alzheimer's, heart disease, lung and other respiratory diseases, digestive system diseases, and so on. Finding better and more specific treatments for blocking excessive inflammation while allowing normal immune function to continue, would extend life for many and reduce morbidity for many more.

Another Way to Add Years to Your Life

2010-06-29T20:20:00.000-07:00

Physorg
Most people spend a third of their lives sleeping. Doing without sleep does not seem to work well, in terms of achieving optimal focus and concentration. The brain seems to need that "down time" for some reason. This may be the reason:Levels of adenosine triphosphate (ATP), the energy currency of cells, in rats increased in four key brain regions normally active during wakefulness. Shown here is the energy surge measured in the frontal cortex, a brain region associated with higher-level thinking. Credit: Courtesy, with permission: Dworak et al. The Journal of Neuroscience 2010.

In the initial stages of sleep, energy levels increase dramatically in brain regions found to be active during waking hours, according to new research in the June 30 issue of the Journal of Neuroscience. These results suggest that a surge of cellular energy may replenish brain processes needed to function normally while awake.

The authors measured levels of adenosine triphosphate (ATP), the energy currency of cells, in rats. They found that ATP levels in four key brain regions normally active during wakefulness increased when the rats were in non-REM sleep, but were accompanied by an overall decrease in brain activity. When the animals were awake, ATP levels were steady. When the rats were gently nudged to stay awake three or six hours past their normal sleep times, there was no increase in ATP.
The authors conclude that sleep is necessary for this ATP energy surge, as keeping the rats awake prevented the surge. The energy increase may then power restorative processes absent during wakefulness, because brain cells consume large amounts of energy just performing daily waking functions. _Physorg
Now that scientists have a clue as to where to look for sleep's regenerative effects on the brain, they can begin to devise alternative ways of stimulating that regeneration -- other than to consume 1/3 of every 24 hour day for that purpose.

Alternative schedules of sleep / wake cycles, napping strategies, electromagnetic stimulation, nutritional or exercise strategies, etc -- there is likely to be workable ways by which an individual could achieve brain ATP regeneration AND redeem some of those 8 hours of sleep for productive or leisure activity. More living, in other words, without endangering one's health.

It is a mere glimpse behind the curtain of sleep, but it could prove to be a useful one. Two extra hours of productive wakefulness over 30 years can give you two and a half extra years of intentional living. If you are just as rested and just as healthy, then there are few reasons not to have more awake time.

Printing Out New Organs and Other Adventures in New Biology

2010-06-18T12:10:00.000-07:00

It may not be long before severely burned persons will be able to lie back and watch while an entirely new skin is printed onto their body -- saving their lives.

The same printer technology that sits on your desk could soon be a common fixture in rebuilding human tissue, treating burns by laying down layers of a patients' own skin or even rebuilding whole organs.
A team at Wake Forest University has built a "bioprinter" that uses cells instead of ink. It even uses an ordinary, off-the-shelf printhead, connected to test tubes full of different cell types instead of wells full of colored inks.

Led by Anthony Atala, director of the Wake Forest Institute for Regenerative Medicine in Winston–Salem, N.C., the team is working on treating burns. Such wounds can be hard to treat, because in severe cases there might not be enough healthy skin on the patient to harvest or culture for a graft.Grafting skin to cover burn wounds is also important for preventing infections, which can be a source of complications. Printing out cells grown in culture would eliminate these problems. Another application is repairing scar tissue.
The breakthrough in using bioprinting for tissue regeneration is the gel used to contain the cells: The mixture must hold the cells in place when they are laid down as well as provide a viable medium where they can be kept alive while they are held in the reservoirs. "It took us seven years," he says. "There's lots of trial and error; this isn't trivial chemistry," he adds.

For building tissue, several printing methods were tried, including three-dimensional CAD and laser printing. But once the group hit on the inkjet method, it turned out to work so well that some of the early work on building tissue was done on modified inkjet printers from a local office supply store.

Other organs have been constructed from cultured cells, but they were built on a scaffolding to give them their three-dimensional shape. Skin doesn't require a matrix because it is relatively flat to begin with.

So far, the system has been tested on mice, which are given wounds similar to burns. Those that were treated with printer-generated cells healed in three weeks, whereas those that were allowed to recover naturally required five weeks. The researchers plan to test the system on bigger animals in the future. The technology is still in the early stages, Atala says. As of yet there is no timetable for human tests or for the publication of the mouse research results.

The Wake Forest group is not just working on skin. Bone tissue and a two-chambered mouse heart have both been successfully printed. The heart was stimulated to beat when the cells were shocked with electricity, and the printed bones have been implanted in mice. _SciAm

Another approach to tissue regeneration is the use of biodegradable polymers as a scaffolding for the growth of replacement cells and tissues.

Here is an idea that is genuinely visionary -- which is exactly the sort of thinking we need to promote if we are ever to get to where we want to go. If we can take our biology to the level that allows us to grow living, breathing, thinking buildings that keep us comfortable and safe, imagine the level of accomplishment that human tissue engineering will have achieved.

A healthy, vibrant, and expansive society requires the best from all of its citizens. We cannot afford to be overly focused upon just one goal. We need to also be developing ideas and processes that may have no immediate use -- but which may indeed be earthshaking and earth saving sometime in the future.

Regenerative Medicine Roadmap

2010-06-07T05:24:00.000-07:00

PDFRegen-RoadmapPDF
FightAging presents a look at what it describes as "The Dawn of the Age of Tissue Engineering", and presents a roadmap of regenerative medicine in PDF format. via Brian Wang

Regenerative medicine is one of several different approaches to life extension and improved human longevity.

Cell therapy involves the adding of younger or progenitor cells, the removal of senescent or destructive cells, and the genetic reprogramming of cells in situ. New and reprogrammed cells then grow within the pre-existing matrix.

Tissue engineering involves the growth of tissues or entire organs within artificial scaffolding. This growth may occur outside the body (for later transplant) or inside the body with in situ tissue engineering.

Cell therapy is the easier approach, but may take several decades of development to achieve the regenerative power that tissue engineering promises to provide within one decade.

Hormonal and growth factor regenerative medicine use chemicals to alter the cells from the outside, in a therapeutic sequence. This approach is even easier than cell therapy, but is also more limited.

There are other regenerative therapies which work via the immune system, and via epigenetic systems, and some of these will come into use within the next decade or two.

Other life extension strategies -- such as cryonics, mitochondrial rejuvenation, technological prostheses, and the total redesign of the human body -- will continue to receive varying levels of support. One should also keep an eye on SENS.

Thymosin Beta 4 Helps Regenerate Damaged Brain in Rats

2010-06-02T11:39:00.000-07:00

The small protein thymosin beta 4 has multiple functions: it moonlights to repair injured tissues [6], has anti-inflammatory efficacy in monocyte/macrophages [7], promotes wound healing [8] and mediates angiogenesis [9]. Tβ4 has been also shown to play a relevant role during the development of different neural cell types in the rat brain [10]. In particular, Tβ4 plays a neurotrophic and antiapoptotic role during the development of the nervous system [11]. __PLoSONE

New research to be reported June 3 at the Annual Meeting of the Society for Academic Emergency Medicine in Phoenix, showed that in adult rats, thymosin beta-4 assisted in the repair of nerve fibres in the brain and in growing new blood vessels.
A synthetic version of a naturally occurring peptide promoted the creation of new blood vessels and repaired damaged nerve cells in lab animals, according to researchers at Henry Ford Hospital in Detroit.

"This successful experiment holds promise for treating clot-induced strokes in humans," says study lead author Daniel C. Morris, M.D., senior staff physician in the Department of Emergency Medicine at Henry Ford Hospital. "Neurorestorative therapy is the next frontier in the treatment of stroke." _SD

This is a potentially important finding for regenerative medicine, given how common cerebral vascular accident is in humans, and how dismal the prognosis typically is afterward.

Thymosin beta-4 is an immune modulating protein, which demonstrates once again how important the brain and the immune system are to one another. Given that Thymosin beta-4 is not a growth factor, as such, it will be important to generate a picture of the entire mechanism involved, for a complete understanding of potential therapies for brain damage, using this protein.

Neural Stimulators Control Inflammatory Processes

2010-06-01T10:06:00.000-07:00

Scientists have known about the connection between the mind-brain and the immune system for many decades. From the "laughter cure" devised by Norman Cousins to mitigate a severe inflammatory disease to the decades old scientific discipline of psychoneuroimmunology, the importance of the connection between the brain and the immune system has been known. A malfunctioning immune system leads to both suffering and an early death, so discovering better ways to dampen an out of control immune response is vital to achieving long and healthy lives.

But finding the best way of controlling immune function by way of the brain has not always been easy. One of the latest attempts at such control comes from a business startup in Boston called Setpoint Medical.
The technology is based on a decade of research elucidating how the brain controls the immune system, particularly inflammation. The treatment has not yet been tested in patients, but based on animal research, scientists hope it will provide an alternative treatment that is more effective and have fewer side effects than existing drugs.

...Over the last decade, Kevin Tracey, an immunologist and neurosurgeon at the Feinstein Institute for Medical Research in Manhasset, NY, has shown that inflammation is controlled in part by the vagus nerve, which carries signals between the brain and a number of visceral organs. Most notably for immune function, it makes direct connections to the spleen, which houses different types of immune cells poised for release at times of infection.

Numerous animal studies have shown that stimulating the vagus nerve can put a brake on the immune system, stopping the rapid recruitment of immune cells to the site of injury or infection. "Think of it as a thermostat for the immune system," says James Broderick, interim president of the company and a partner at Morgenthaler Ventures, Setpoint's key investor. "This reflex puts a damper on the immune system."

The effect is similar to that of a popular class of drugs, called TNF alpha blockers, used to treat arthritis and other autoimmune diseases. These drugs block the release of an immune signaling molecule that is central to inducing inflammation. While they work effectively in 50 to 70 percent of patients, the drugs can lose their effectiveness over time and have been linked to some serious side effects, such as infection and cancer. Vagus nerve stimulation blocks both the signal molecule and other cytokines involved in inflammation. _TechnologyReview
This novel approach to treating autoimmune diseases and hyper-immune responses may be used instead of drug treatment, or along with drug treatment to allow lower doses of drugs.

Brain Cell Regeneration Using Reprogrammed Astroglia

2010-05-19T07:32:00.000-07:00

The brain consists of two major cell types: neurons, which transmit information, and glial cells, which support and protect neurons. Interestingly, evidence suggests that some glial cells, including astroglia, can be directly converted into neurons by specific proteins, a transformation that may aid in the functional repair of damaged brain tissue. However, in order for the repaired brain areas to function properly, it is important that astroglia be directed into appropriate neuronal subclasses. In this study, we show that non-neurogenic astroglia from the cerebral cortex can be reprogrammed in vitro using just a single transcription factor to yield fully functional excitatory or inhibitory neurons. We achieved this result through forced expression of the same transcription factors that instruct the genesis of these distinct neuronal subtypes during embryonic forebrain development. Moreover we demonstrate that reactive astroglia isolated from the adult cortex after local injury can be reprogrammed into synapse-forming excitatory or inhibitory neurons following a similar strategy. Our findings provide evidence that endogenous glial cells may prove a promising strategy for replacing neurons that have degenerated due to trauma or disease. _PLOS

Scientists from the Helmholtz Center and Ludwig-Maximilians University in Munich, have used a virus to reprogram brain helper cells -- astroglia -- into actual neurons. They were able to convert astroglia from early post-natal and adult mouse brains into either excitatory or inhibitory neurons, depending upon the transcription factors which were introduced.
The study adds to growing evidence that certain cell types can be transformed directly into other cell types without first being converted into stem cells. Researchers have previously transformed skin cells into neurons, and one type of pancreatic cell into another. Marius Wernig, a coauthor of the skin cell study and a stem cell biologist at Stanford University, says there's a growing awareness that it may not be necessary to erase a cell's existing identity before giving it a new one.

...this latest study "means that these astroglial cells could be converted in the brain" without the need for a transplant. Berninger says that one of the next challenges is to determine whether these reprogrammed neurons can survive and function in a living brain.

Fortunately, the brain seems to have a ready source of astroglia. When the brain is injured, these cells proliferate, similar to the way the skin repairs itself after a wound. The researchers found they could also derive neurons from injury-induced astroglia taken from the brains of adult mice. _TechnologyReview
More:we first aimed at a more potent neuronal reprogramming by inducing higher and more persistent expression of neurogenic fate determinants in astroglial cells. This allowed us not only to obtain fully functional neurons that also establish synapses from astroglial cells in vitro but also to demonstrate that distinct neurogenic transcription factors, such as on the one hand Neurog2 and on the other Dlx2 alone or in combination with Mash1, can indeed instruct the selective generation of different neuronal subtypes, such as glutamatergic and GABAergic neurons, respectively. Moreover, we found that the reprogramming efficiency of postnatal cortical astroglia towards GABAergic neurons by Dlx2 could be enhanced by first expanding the astroglial cells under neurosphere conditions prior to forced expression of Dlx2. Given that following brain injury reactive astroglia from the adult cerebral cortex de-differentiate, resume proliferation, and can give rise to self-renewing neurospheres in vitro [16], we finally show that neuronal reprogramming and subtype specification are not restricted to postnatal stages but can also be achieved from adult cortical astroglia responding to injury. _PLOS
The findings are a striking reminder that nature offers us many more possibilities than we can presently conceive of. But perhaps we will grow in our conceptual capacity, over time.

The possibility of regenerating brain tissue in situ -- without the need for inserting new cells from elsewhere -- offers new hope for brain trauma, infection, infarct, atrophy, and senility. But it also offers a distinctly new possibility which most observors are not quite ready to think about -- much less discuss.

I am referring to the possibility of growing entirely new neural networks in situ, from astroglia. The possibility that humans can induce their own brains to create entirely new brain centers and pathways, using more advanced forms of such techniques, should not be overlooked.

There is currently a race between biological methods of repairing and enhancing human organs, and technological methods of compensating for organ damage or loss -- the cyborg approach. A cyborg may utilise nano-technological enhancement, and thus manifest no outward sign of distinction from standard normal humans. The same would be true for most biological enhancements or remediation.

This lack of overt differences between ordinary persons and enhanced persons is quite important to most military uses of enhanced individuals, and to virtually all covert uses by government and other organisations.

But these tools of transformation are not likely to remain limited to deep pocketed groups and individuals. Garage biohackers are not as uncommon as you might think, and are performing a similar service for bio-hacking as the garage techno-hackers performed for microcomputers in the early days. And it is also extremely likely that persons involved in expensive and large scale research into bio-transformation technologies will set off on their own as they discover the ability to profit from their technical knowledge and skills.

Cross-posted at Al Fin

Tricks of Epigenetic Memory

2010-05-18T20:29:00.000-07:00

It is common knowledge that a person's memory tends to get a bit foggy as he ages. A young person's memory tends to be crisper and quicker than that of a person in senescence. But it is possible that there is a means within our grasp by which we can turn back the clock in the aging brain -- back to a time of quicker and clearer recall, and a stronger grasp of new knowledge.
A new study published in Science sheds some light on how “memory disturbances” in an aging mouse brain are associated with altered “hippocampal chromatin plasticity” — the combination of DNA, histones, and other proteins that make up the chromosomes associated with the hippocampus. Specifically, the study describes an acetyl genetic switch that produces memory impairment in aging 16-month-old mice. Because the acetyl wasn’t present in young 3-month-old mice, the study concludes that it acts as a switch for a cluster of learning and memory genes.

...Dr. Fischer’s research shows that when young mice are learning, an acetyl group binds to a particular point on the histone protein. The cluster of learning and memory genes on the surrounding DNA ends up close to the acetyl group. This acetyl group was missing in the older mice that had been given the same tasks. By injecting an enzyme known to encourage acetyl groups to bind to any kind of histone molecule, Fischer’s team flipped the acetyl genetic switch to the “on” position in the older mice and their learning and memory performance became similar to that of 3-month-old mice. _hplus
More:Dr Fischer, of the European Neuroscience Institute in Goettingen, Germany, pinpointed a tiny protein called H4K12 that controls genes key to memory and learning in the mouse brain.

...In an accompanying article, Professor David Sweatt , a U.S. neurobiologist, said that turning on H4K12 was likely to help with both Alzheimer's and age-related memory loss.
He said the German results 'provide important proof of principle that this might be a viable approach to therapeutic interventions in ageing'.
'These studies will hopefully lead to more effective prevention strategies to improve quality of life in the aged, as well as contribute to a better understanding of memory function,' he added.
The treatment of other brain conditions, such as schizophrenia and Parkinson's disease, could be improved by finding other switches that act in a similar way.
Dr Marie Janson, of the Alzheimer's Research Trust, said: 'Although in mice, this research gives us clues about how memories are formed and function in the brain.
'We now need to find out if the same processes happen in the human brain.
'This understanding is vital if we are to develop ways to protect the ageing brain from cognitive decline.
'Alzheimer's and other dementias are complex, with many things happening in the brain, so it's likely that we'll need several drugs to treat them effectively._DailyMail

Brain function is inextricably tied to genetic function. The relationship is certainly of a circular nature. If we are to learn to live long and fulfilling lives, we will need to undertand ourselves better, at a much deeper level than we once thought possible.

Stem Cells to Restore Your Hearing, Your Heart, Your Teeth

2010-05-15T06:17:00.000-07:00

Stanford University researchers have developed a way to grow replacement "hair cells" for the inner ear, in mice. The hair cells are responsible for hearing, and the cumulative loss of hair cells over a lifetime result in permanent hearing loss. If humans could learn to regenerate the hair cells in the inner ear, hearing loss could be reversed without the need for electronic devices such as cochlear implants or hearing aids. Source via Brian Wang

Geron scientists have demonstrated the safety of GRNCM1 (cardiomyocites or stem cells) for replacing damaged heart tissue. This treatment, once approved, is likely to be used to treat chronic heart failure -- a significant cause of death and disability worldwide.
Source 1 (via Brian Wang), Source 2

Columbia University researchers are developing a method for growing replacement teeth "in place", inside the actual socket of the lost tooth. The method utilises stem cells to re-grow the tooth along with accompanying soft tissue support. This approach will do away with the need to use hardware implants, or to grow teeth outside the body in culture media.
Source via Brian Wang

The re-growth of body organs in place -- using the original tissue matrix as a scaffolding -- is a safer approach than re-growing organs outside the body, then surgically implanting them. Both approaches will probably become common, but in circumstances where in situ stem cell replacement is effective, most persons will likely opt for that approach.

Stem Cells from Endometrial Tissue Reverse Parkinson's?

2010-05-07T08:31:00.000-07:00

Scientists at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), have injected endometrial stem cells into the brains of mice with an induced form of Parkinson's Disease. The injected stem cells began producing dopamine -- the neurotransmitter that is deficient in Parkinson's.
The finding raises the possibility that women with Parkinson's disease could serve as their own stem cell donors. Similarly, because endometrial stem cells are readily available and easy to collect, banks of endometrial stem cells could be stored for men and women with Parkinson's disease.

"These early results are encouraging," said Alan E. Guttmacher, M.D., acting director of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the NIH Institute that funded the study. "Endometrial stem cells are widely available, easy to access and appear to take on the characteristics of nervous system tissue readily."

Parkinson's disease results from a loss of brain cells that produce the chemical messenger dopamine, which aids the transmission of brain signals that coordinate movement. This is the first time that researchers have successfully transplanted stem cells derived from the endometrium, or the lining of the uterus, into another kind of tissue (the brain) and shown that these cells can develop into cells with the properties of that tissue. The findings appear online in the Journal of Cellular and Molecular Medicine. _SD

An optimal form of brain regeneration would likely combine the use of exogenous growth factors and stem cells, along with the stimulation of endogenous stem cell and growth factor production. There is a lot to be learned about how the brain works normally, and what goes wrong in degenerative conditions, trauma, ischemia, and aging.

Even an Old Hippocampus Continues Making New Neurons

2010-05-06T15:53:00.000-07:00

The brain maintains neuronal stem cells throughout life, according to scientists at Max Planck Institute who studied the phenomenon of lifelong neurogenesis in mouse brains.
The precise factors that influence the reactivation of dormant stem cells are not yet clear. The cells can, however, be stimulated to divide again. The scientists observed more newborn hippocampal neurons in physically active mice than in their inactive counterparts. "Consequently, running promotes the formation of new neurons," says Verdon Taylor. Pathological brain activity, for example that which occurs during epileptic seizures, also triggers the division of the neuronal stem cells.

...The presence of neurons that are formed over the course of life has also been demonstrated in the human hippocamus. Therefore, scientists suspect that different types of active and inactive stem cells also arise in the human brain. It is possible that inactive stem cells in humans can also be activated in a similar way to inactive stem cells in mice. _Physorg
If increased physical activity can stimulate new nerve cell generation, a strong argument could be made for encouraging a more active physical regimen throughout a person's lifetime. Such a finding argues for the importance of physical rehabilitation as a treatment for neurodegenerative diseases, and after a stroke or other necrotising brain injury.

Making new neurons is not the same thing as being sure the neurons are healthy and optimally functioning. Scientists are learning more about the micro-differences between healthy neurons and those that are not so healthy. The delicate micro-structures called dentritic trees or arbours, are important to good communication within the neuronal networks. And the health of these dendritic trees depends upon optimal quantities of certain cell proteins -- which are under genetic control.

And that genetic control is of course under the control of transcription factors which are influenced by a number of other things -- some under genetic control, and some influenced by the evironment.

Finding more ways that a person can optimise the generation of healthy new neurons -- and to maintain the health of those in existence -- will be worth all the time it will take.

A Second Level of Gene Transcription Control

2010-04-30T07:06:00.000-07:00

Controlling gene expression is an important key to controlling ageing, cancer, diseases of degeneration and autoimmunity, and virtually any other mechanism of human health and pathology. As scientist learn more about the mechanisms of gene expression, they also discover new ways of intervening to prevent or treat disease. The following article discusses the ongoing clarification of an important added complexity of gene expression that will certainly be exploited for good effect before long.
A new study published online today (April 29) in Cell helps drive home just how widespread this second level of gene control is, and implicates a cancer-causing transcription factor as a major player in the process.

"This is another piece in the puzzle that demonstrates controlling the elongation phase of transcription" -- the production of messenger RNA as the transcriptional apparatus propagates down the gene -- "is one of the more important control mechanisms," said biochemist David Price of the University of Iowa, who was not involved in the study. "[This] paper is going to help convince the field that this is just the way it is."

Scientists once believed that transcription factors promoted gene expression simply by recruiting RNA polymerase II (Pol II) machinery to the promoter region of their target genes, and letting the Pol II take over from there. But over the last 20 years, several lines of evidence indicated that once bound to the promoter, Pol II pauses, or stalls, just a little ways down the transcript, and needs another signal (such as a transcription factor) to continue transcribing the gene. Recent evidence suggests that this pause is a widespread phenomenon in the genome, but "there's been some reluctance in the transcription community to accept that there are these polymerases poised [just past the start site] all throughout the human genome," Price said.

Exploring the role of this mechanism of gene control in mouse embryonic stem cells (ESCs), molecular biologist Richard Young of the Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology and his colleagues have all but eliminated that doubt. They found evidence of paused polymerases on the vast majority of genes -- both those actively being transcribed and those that remained silent.

"We're thinking now that at all genes where RNA polymerase II initiates transcription, there is a pause step," Young said. "So even genes that are being currently and actively transcribed, polymerase initiates [transcription], but must go through this pause checkpoint before it's allowed to proceed to elongation."

The team further showed that the well-studied transcription factor c-Myc, which is involved in cell self-renewal and proliferation and has been implicated in 15-30 percent of human cancers, is an example of the additional factor needed to push Pol II past the pause. Instead of promoting gene expression by recruiting Pol II to the genes, c-Myc appears to release already-initiated polymerases from this paused stage. It does so by recruiting a protein known as positive transcription elongation factor b (P-TEPb) to release the Pol II to finish what it started.

Understanding the details of this mechanism of gene control could thus have important implications for the treatment of a variety of ailments, said molecular biologist and clinician B. Matija Peterlin of the University of California, San Francisco, who also did not participate in the research. "I think it brings a whole new aspect to not just cancer [research] but" other diseases as well, Peterlin said. "If you attenuate the activity of P-TEFb, you might be able to [develop] a non-gene-modifying way treat a lot of human diseases."

P.B. Rahl, et al., "c-Myc regulates transcriptional pause release," Cell:141,1-14,2010.

Read more: More support for transcription trick - The Scientist - Magazine of the Life Sciences http://www.the-scientist.com/blog/display/57384/#ixzz0malxMCbC _the-scientist

Nano-Magnets Lead Stem Cells to Damaged Heart

2010-04-09T08:46:00.000-07:00

A promising way of healing damaged heart tissue involves combining stem cells with nano-magnets. The magnetised stem cells are then steered to the site of damage, using magnetic fields.
"Stem cell therapies show great promise as a treatment for heart injuries, but 24 hours after infusion, we found that less than 10 percent of the stem cells remain in the injured area," said Eduardo Marbán, M.D., director of the Cedars-Sinai Heart Institute. "Once injected into a patient's artery, many stem cells are lost due to the combination of tissue blood flow, which can wash out stem cells, and cardiac contraction, which can squeeze out stem cells. We needed to find a way to guide more of the cells directly to the area of the heart that we want to heal."
Marbán's team, including Ke Cheng, Ph.D. and other researchers, then began a new animal investigation, loading cardiac stem cells with micro-size iron particles. The iron-loaded cells were then injected into rats with a heart attack. When a toy magnet was placed externally above the heart and close to the damaged heart muscle, the stem cells clustered at the site of injury, retention of cells in the heart tripled, and the injected cells went on to heal the heart more effectively.
"Tissue viability is enhanced and heart function is greater with magnetic targeting," said Marbán, who holds the Mark Siegel Family Foundation Chair at the Cedars-Sinai Heart Institute and directs Cedars-Sinai's Board of Governors Heart Stem Cell Center. "This remarkably simple method could easily be coupled with current stem cell treatments to enhance their effectiveness." _Physorg
Image Source

The combination of stem cells with nanotechnology provides another synergistic surprise, loaded with hope for future cures and life extension potential.

Tomorrow's medical treatments will be more individualised, more targeted to specific systems and tissues. As a result, the collateral damage will be lessened, interventional dosing and exposure can be moderated, and a desired outcome can be made more likely.

Switching Off Cancer Using Nanoparticles

2010-04-08T18:59:00.000-07:00

Cuanas
Scientists at Cal Tech in Pasadena have used targeted nanoparticles to alter the gene expression of cancer cells in human cancer patients. Their phase 1 clinical trial established the efficacy of their targeting approach and was published in the 21 March advanced online Nature.
Lead author Dr Mark E Davis, the Warren and Katharine Schlinger Professor of Chemical Engineering at Caltech, told the press that in principle:

"Every protein now is druggable because its inhibition is accomplished by destroying the mRNA."

"And we can go after mRNAs in a very designed way, given all the genomic data that are and will become available," he added.

However, as is often the case, what looks straightforward in theory is fraught with obstacles when you try and apply it in practice. One such difficulty, when trying to apply RNAi technology to humans is, how do you deliver such tiny, fragile molecules, the small interfering RNAs (siRNAs), to the tumors?

Senior author Dr Antoni Ribas, an associate professor of medicine and surgery and a researcher at UCLA's Jonsson Comprehensive Cancer Center, said:

"There are many cancer targets that can be efficiently blocked in the laboratory using siRNA, but blocking them in the clinic has been elusive."

Davis and colleagues had a solution: they had already been working on ways to deliver nucleic acids into cells before RNAi was discovered. They eventually came up with a method featuring four components, one of which is a unique polymer that can assemble itself into a targeted nanoparticle that carries siRNA.

Davis explained that their nanoparticles can take the siRNAs into the targeted site within the body, and when they reach their target, the cancer cells inside the tumor, the nanoparticles enter the cells and release the siRNAs.

The researchers used a new method developed at Caltech to find and image the nanoparticles inside cells biopsied from the tumors of several patients taking part in the trial.

They also found that the more nanoparticles a patient was given, the more were present in the tumor cells: thus establishing there was a dose-dependent response.

But what was even better, said Davis, was they found evidence the siRNAs had done their job: in the cells they analyzed, which had been targeted to prevent production of the cell-growth protein ribonucleotide reductase, they found the corresponding mRNA had been degraded. Thus effectively the siRNAs had silenced the gene that was fuelling cancer growth.

Davis explained that this was the first time that anyone has found an RNA fragment from patient cells showing that the RNAi mechanism had severed the mRNA at exactly the correct base:

"It proves that the RNA interference mechanism can happen using siRNA in a human," said Davis.

Ribas said:

"This research provides the first evidence that what works in the lab could help patients in the future by the specific delivery of siRNA using targeted nanoparticles."

"We can start thinking about targeting the untargetable," he added. _MedicalNews

As the authors say, this is just the beginning. Silencing gene expression by targeting the mRNA is only a temporary approach. If such treatment kills all of the cancer cells -- and leaves normal cells alone -- then being only temporary will not be an impediment.

But in many types of cancer -- and other disease -- it will not be enough merely to block the offensive mRNA. You will want to alter the DNA itself to put a permanent stop to the flow of a particular unwanted mRNA. That will require a different approach altogether.

The challenge is vast and seemingly unending. But it is worthwhile.

H/T Cuanas

New Hope for Treating Autoimmune Diseases

2010-04-08T18:40:00.000-07:00

Cell
The autoimmune diseases cause untold pain, misery, and hardship -- not to mention expense -- throughout the human lifespan. When the person's immune system attacks other cells in his own body, treatment options are generally limited and sub-optimal. But now, researchers at the University of Alberta, Calgary, have devised a treatment (and prevention) for Type 1 diabetes which may lead to a revolution in the treatment and prevention of autoimmune diseases -- such as multiple sclerosis, rheumatoid arthritis, lupus, and many more.
Researchers from the University of Calgary in Alberta, led by Dr. Pere Santamaria, were looking to halt the autoimmune response that causes type 1 diabetes, but do so without damaging the immune cells that control and regulate the immune system or that protect against infections. So the team focused on developing a highly targeted antigen-specific immunotherapy - one, they explained, that could address the "internal tug-of-war between aggressive T cells that want to cause the disease and weaker T cells that want to stop it from occurring."

The researchers produced a unique vaccine comprising nanoparticles, which are thousands of times smaller than the size of a cell. They coated the particles with type 1 diabetes-relevant peptides, or protein fragments, that were bound to certain molecules that play a critical role in immune cell communication (called MHC molecules).

In the mice, the nanoparticle treatment expanded a type of regulatory T cell -- these cells ultimately suppressed the aggressive immune attack that destroys the insulin-producing beta cells of the pancreas. The researchers noted that the expanded cells shut down the immune attack by preventing autoreactive immune cells from being stimulated, either by the peptide contained in the vaccine or by any other diabetes autoantigen presented simultaneously by antigen-presenting cells. With the immune response that causes diabetes blocked, mice with type 1 diabetes regained normal blood sugars. And those that would have contracted the disease didn't.

The study also provides important - and promising - insight into the ability to translate these findings into therapeutics for people: Nanoparticles that were coated with molecules specific to human type 1 diabetes were able to restore normal blood sugar levels in a humanized mouse model of diabetes (that is, a mouse that has been genetically altered to biologically simulate type 1 diabetes in people). _ jdrf

Article abstract from Cell

H/T Brian Wang

Science is slowly but surely decoding the complex signaling involved in life, disease, and ageing. With the better tools being provided by advanced genetics, nanotechnology, immunology, and information technology, it is easy to feel that there are no secrets of life that will not be unwrapped and decoded sooner or later.

Human Cell Aging Reversed by Biotime

2010-04-07T06:37:00.000-07:00

Biotime researchers report the successful resetting of the "age clock" of mature human cells back to the embryonic age. This was apparently accomplished using telomeric technology similar to what Geron has been working on.
In the article, BioTime and its collaborators demonstrate the successful reversal of the developmental aging of normal human cells. Using precise genetic modifications, normal human cells were induced to reverse both the "clock" of differentiation (the process by which an embryonic stem cell becomes the many specialized differentiated cell types of the body), and the "clock" of cellular aging (telomere length). As a result, aged differentiated cells became young stem cells capable of regeneration.
_NextBigFuture

More links, videos, and information from Brian Wang and at the BioTime website.

Hydrogen Sulfide Suspended Animation Video

2010-03-22T09:37:00.000-07:00

Roth's technique replaces inhaled oxygen with hydrogen sulfide. Normally toxic, hydrogen sulfide has the curious ability to alter the mammalian metabolism when applied in a cold environment. Using this technique, Roth has already managed to place lab animals into suspended animation, and safely bring them back. When in a suspended state, the body can better cope with the deadly oxygen deprivation that results from shock, massive blood loss, and heart attacks.
Source

The 1000 Year Old Brain? Can They Last?

2009-11-15T11:50:00.000-08:00

Aubrey de Grey claims that the first person to live 1,000 years is alive right now. Perhaps. But would anyone alive right now wish to live 1,000 years with a senile brain? Probably not. That is why it is so important to learn all we can about our brains, so that we can make the necessary improvements that will allow us to stay sharp, clear, and responsive to the many changes that the next 1,000 years will bring.

A World of Manics, Where No One is Depressed?

University of Maryland researchers have taken mice and knocked out PKCI/HINT1 genes -- resulting in mice that do not get depressed or anxious.

Wang said, "Although we don't yet know why the deletion of the gene altered the mood status of the mice, what we have learned about the importance of this gene in mood function and its involvement in human mental disorders is interesting. The protein encoded by this gene could be a potential drug target for development of diagnostic or therapeutic agents that one day might be used for depression, bipolar or schizophrenia disorders. In addition, the knockout mice might be useful as a model to study mania, as there is no other animal model available yet. __MNT

When thrown in the deep end of the pool, these PKCI/HINT1 knockout mice never gave up in despair, when all other mice simply rolled over and drowned. They were literally "never say die" mice. Imagine a world of such people.

Excitable Nerves, They All Said

Sometimes nerves can "excite themselves to death." This over-excitation of NMDA glutamate receptors may lead to Alzheimer's, Parkinson's, and multiple sclerosis -- among other neurodegenerative diseases.

....the N-methyl-D-aspartate receptor belongs to a family of cellular receptors that mediate excitatory nerve transmission in the brain.

Excitatory signals represent the majority of nerve signals in most regions of the human brain. One theory of causation in Alzheimer's, Parkinson's and multiple sclerosis posits that excessive amounts of the excitatory neurotransmitter, glutamate, can cause an overstimulation of glutamate receptors, including the NMDA receptor. Such excitotoxicity, the theory holds, can cause nerve-cell death and subsequent neurological dysfunction.

...The search is well under way for molecules that can shut down the NMDA receptor with much greater specificity. _MNT

Memories to Last 1000 Years?

Humans have short term memories (STMs) and long term memories (LTMs). Short term memory is necessary for maintaining a train of thought, or for remembering why you tied that string around your finger an hour or two ago. Long term memory is for remembering things that happened to you more than a day or so ago. These memories are formed and farmed out by the hippocampus, and the system usually works well for a lifespan of 70 or 80 years. But what happens when we live 1,000 years, and desperately need to remember something that happened 899 years ago?

Scientists have known that memories first form in the hippocampus and are later transferred to long-term storage in other parts of the brain. For some amount of time the memory resides both in the hippocampus and elsewhere in the brain. What’s not been known is how, after a few months or years, the memory is gradually cleared from the hippocampus.

Researchers have also debated the role of neurogenesis in learning and memory. The hippocampus is one of only two places in the adult brain where scientists know that new neurons form. On the basis of previous studies, many researchers think new neurons stabilize memory circuits or are somehow otherwise necessary to form new memories.

The new study suggests the opposite: Newborn neurons weaken or disrupt connections that encode old memories in the hippocampus.

Kaoru Inokuchi, a neuroscientist at the University of Toyama in Japan, and his colleagues used radiation and some genetic tricks to block neurogenesis in rats and mice that had been trained to fear getting a mild electric shock when placed in a particular cage. Control animals, with normal neurogenesis, eventually were able to bypass their hippocampi and retrieve the fear memory directly from long-term storage. But animals in which neurogenesis had been blocked still depended on the hippocampus to recall the fear memory, the researchers found.

Running on an exercise wheel, which boosts neurogenesis, also sped the rate at which old memories were cleared from the hippocampus. __Wired

Surviving the Addiction Bottleneck

The human brain has to survive through the treacherous years of childhood, adolescence, and early adulthood in order to gain the wisdom and experience to know how to live, and what to avoid like the plague. Children, adolescents, and young adults are prone to experimenting with drugs, alcohol, and high-risk / low reward behaviours. If the child becomes a crack whore or even an adolescent drunk or pothead like the US president, the 1,000 year prognosis can be very grim.

We need good ways of reversing the brain warp induced by early and habitual drug use.

Medical researchers led by Stephen Dewey at The Feinstein Institute for Medical Research and Dr. Jonathan Brodie of New York University School of Medicine recruited parolees who were cocaine dependent, each using an average of two grams of cocaine daily for nine years.

While half the participants in the study received a placebo powder mixed into their juice each day, half got a powder containing vigabatrin. After three months, 14 of the 50 study participants who got vigabatrin each day were able to abstain from cocaine use during the final three weeks of the study, compared with only 4 of the 53 who received the placebo. _MoneyTimes

It's a start. And in animals, the same drug reduces drug use for most every addictive substance. Of course, it will be harder to make up for the psychological neotenisation caused by poor childraising, abominable educational practises, and a horrifically dumbed down popular culture.

Does Evolution's Arrow Point to Smaller Human Brains?

Human populations that evolved nearer the equator ended up with generally smaller brains, and typically with lower IQ, than human populations that evolved farther from the equator. Anthropologist John Hawks says that the future may be bringing yet smaller brains to the entire global population.
“We know the brain has been evolving in human populations quite recently,” University of Wisconsin-Madison (UWM) paleoanthropologist John Hawks explains, quoted by LiveScience.

“When it comes to recent evolutionary changes, we currently maybe have the least specific details with regard [to] the brain, but we do know from archaeological data that pretty much everywhere we can measure – Europe, China, South Africa, Australia – that brains have shrunk about 150 cubic centimeters, off a mean of about 1,350. That's roughly 10 percent. As to why is it shrinking, perhaps in big societies, as opposed to hunter-gatherer lifestyles, we can rely on other people for more things, can specialize our behavior to a greater extent, and maybe not need our brains as much,” the expert adds. _Softpedia
Modern cultures of hyper-specialisation may lead to even greater shrinking of the human brain. That could be bad for that 1,000 year lifespan.

Smaller brains are typically less intelligent, and will probably be less able to adapt to the lightspeed changes that will hit human populations like truckloads of bricks, every few years to every few dozen years.

Cross-posted at Al Fin

Stem Cell Advances

2009-11-09T15:35:00.001-08:00

Any adult cell can become a stem cell. This is a striking finding from the Cambridge, Mass. researchers.
“Essentially, all cells have the potential to become pluripotent. It is something that seems to happen to the cells under these conditions stochastically — that is, in a continuous, but probabilistic fashion,” Jaenisch explains. _Softpedia

Stem cell treatment restores limb function in rats with cervical spine injuries. The UCI team used human embryonic stem cells (pre-oligodendrocytes) that "rebuilt myelin, stopped tissue death and triggered nerve fiber regrowth".

Patients with advanced leukemia successfully treated with stem cells. Of the 58 patients, 35% survived 3 years -- an exceptionally good result for patients at such an advanced stage.

New technique developed to separate "safe" from "unsafe" stem cells before therapy. Stem cells vary in their likelihood to grow out of control and cause malignancies. "Undifferentiated" stem cells are more likely to lose control of growth.
Scientists from Invitrogen and the Buck Institute for Age Research, located in Novato, California, collaborated in developing this innovative solution that depletes greater than 99% of undifferentiated human embryonic stem cells from differentiated populations. They are presenting data on this new technology at the International Society for Cellular Therapy Meeting in San Diego. __LabmateOnline

Stem cells provide the bricks and mortar for constructing human tissues and organs. We are just beginning to learn how to create them, and to use them safely and efficaciously. In ten years -- if the US biomedical system has not been completely destroyed by government intervention -- we will look back to the present, amazed that human medicine was ever so primitive and hopelessly ineffective.

SENS4 Conference in Cambridge England Underway

2009-09-05T09:29:00.001-07:00

Kristen Fortney from Ouroborus blog is covering the 4th Strategies for Engineered Negligible Senescence conference, presently underway in Cambridge, England. Below are some excerpts of Kristen's coverage, courtesy of Fight Aging:

SENS4, Session 1: Combating oxidation

Cathy Clarke tested an original and interesting approach to avoiding free radical damage to poly-unsaturated fatty acids, or PUFAs: isotope reinforcement. ... The basic idea here, explained in an earlier paper, is very simple: heavier isotopes make stronger bonds, so isotope-reinforced PUFAs will be more resistant to free radical attack. Will these results transfer to higher organisms? Is there any chance that the deuterium could get incorporated into other molecules, stabilizing proteins that we want to degrade? The authors plan to follow up this study in worms and mice.

SENS4, Session 3: Optimising metabolism against aging

Stephen Spindler described his (ongoing) project to screen a large number of potential lifespan-affecting compounds in mice - so far, several candidates look promising. Interestingly, he also argued that the majority of previous studies measuring the effects of various compounds on rodent life expectancy suffer from serious flaws. In particular, he argued that many of them were confounded by a possible calorie restriction effect: mice are picky eaters, and if you change their diet by adding some compound to it, they will often eat less of it.

SENS4, Session 4: Adult regenerative capacity

Brandon Reines presented a counterintuitive result on regeneration: sometimes old animals have a higher regenerative capacity than young animals. In particular, if you punch a hole in the ear of a young mouse, then it won’t heal; but in a middle-aged mouse it will heal completely. He argued that this happens because mouse ear connective tissues never fully differentiate, and suggested that other neural-crest-derived connective tissues might show similar properties.

SENS4, Session 5: Eliminating recalcitrant intracellular molecules: the lysosome

John Schloendorn discussed ongoing work at the SENS Foundation Research Center to develop new enzymes that can degrade harmful intracellular junk that accumulates with age. So far, they have discovered enzymes that can degrade A2E and 7-ketocholesterol, which are implicated in macular degeneration and osteoporosis, respectively. Their next step will be to construct a drug delivery system to get these enzymes to lysozomes ... On the lighter side, Schloendorn also described some of the Center’s methods for building functional lab equipment on the cheap, all good examples for aspiring DIY biologists.

SENS4, Session 6: Eliminating recalcitrant intracellular molecules: other

Claude Wischik spoke about preventing aggregation of tau protein, which is implicated in Alzheimer’s disease. Clinical trials of their aggregation-inhibiting drug Rember are promising: it seems to slow the down the rate of cognitive decline in patients with mild to moderate Alzheimer’s disease.

SENS4, Sessions 9 and 10: Rejuvenating extracellular material

Kendall Houk gave a very interesting talk on computationally designing enzymes from scratch. They plan to apply their recently published protocol to develop enzymes that can reverse the formation of Advanced Glycation End-products (AGEs) - sugar-modified proteins that accumulate with age and are implicated in several age-related diseases. _links to more information

Ouroborus is updating Kristen's coverage as it comes in.

Twitter updates

Aubrey de Grey's SENS initiative has achieved prominence in scientific gerontology, thanks to financing from the Methuselah Foundation. Under most government health care and pension systems, long life is a bad thing, since the longer you live, the longer the government has to support your existence. That may be why so little progress was made under government financed gerontology research.

With private funding via SENS, expect much more progress. The same applies to private financing of space launch, and other crucial innovations. The private sector is all about getting results. The government is all about soaking up as many resources as possible, growing as large as possible, and employing as many public sector union members as possible.

Cross posted at Al Fin

Giving Babies Healthy Mitochondria

2009-08-27T11:51:00.000-07:00

Scientists at the Oregon National Primate Center have succeeded in producing healthy rhesus infants using the egg nucleus from one female transplanted into the enucleated cytoplasm of another female. The mitochondria from the cytoplasmic component reproduced normally alongside the nuclear material from the nuclear component, without contamination of mitochondria from the nucleus donour.

For their experiments, Mitalipov and his colleagues extracted DNA from the nucleus of monkey eggs; the nucleus contains the genes for most of a creature's traits. The researchers then transplanted that DNA into eggs from other females that had healthy mitochondrial DNA but from which the nuclear DNA had been removed.

They then fertilized the eggs in the laboratory and transferred 15 of the resulting embryos into the wombs of nine females. Two twins were born -- named Mito and Tracker -- along with two other offspring, Spindler and Spindy. So far, all the offspring appear to be healthy. _WaPo_via_ImpactLat

This research shows the way to new techniques for using cytoplasmic donour eggs to assure healthy offspring for mothers who may carry deficiencies for mitochondria -- which have their own DNA, for the most part.

Assuring mitochondrial health is one of the most important bases for overall health and longevity.

While this technique will only work for animals at the egg stage, there is no reason not to believe that advanced forms of mitochondrial culturing and transplant will not occur. Eventually, interventional genetic therapies will be developed which will move most of the genetic material from the mitochondria -- where it is subjected to extreme mutagenic oxidative stress -- to the nucleus where it would be better protected. That is one of the foundations of the SENS approach to longevity.

Hope for the Aging Brain

2009-07-03T12:05:00.000-07:00

An intriguing finding from the University of South Florida offers new hope for rejuvenating aged and amyloid-clogged brains.

GCSF is a blood stem cell growth factor or hormone routinely administered to cancer patients whose blood stem cells and white blood cells have been depleted following chemotherapy or radiation. GCSF stimulates the bone marrow to produce more white blood cells needed to fight infection. It is also used to boost the numbers of stem cells circulating in the blood of donors before the cells are harvested for bone marrow transplants. Advanced clinical trials are now investigating the effectiveness of GCSF to treat stroke, and the compound was safe and well tolerated in early clinical studies of ischemic stroke patients.

....The researchers showed that injections under the skin of filgrastim (Neupogen®) — one of three commercially available GCSF compounds — mobilized blood stem cells in the bone marrow and neural stem cells within the brain and both of these actions led to improved memory and learning behavior in the Alzheimer’s mice. “The beauty in this less invasive approach is that it obviates the need for neurosurgery to transplant stem cells into the brain,” Dr. Sanchez-Ramos said.

Based on the promising findings in mice, the Alzheimer’s Drug Discovery Foundation is funding a pilot clinical trial at USF’s Byrd Alzheimer’s Center. The randomized, controlled trial, led by Dr. Sanchez-Ramos and Dr. Ashok Raj, will test the safety and effectiveness of filgrastim in 12 patients with mild to moderate Alzheimer’s disease _Biosingularity

As noted, the reversal of Alzheimer's brain damage occurred in research mice -- a mouse "Alzheimer's model" involving 52 aged study mice. If the trial involving 12 human patients shows promise, expect several larger human studies.

In my opinion, Alzheimer's Disease is every bit the crisis that AIDS represents, and the search for therapies for Alzheimer's should be given at least as much funding and regulatory impetus as the research effort into HIV and AIDS has been given. Unfortunately, President Obama and his administration are sending signals that advanced medical care for the aged will be given an extremely low priority under Obamacare.

Another stem cell growth factor -- EGFL7 -- may play a large role in therapies for a wide array of conditions involving brain degeneration and damage.

The findings of Schmidt and Dikic offer a plethora of medical applications. Maturation of adult stem or precursor cells is significant for the development of multiple tissues, e.g. in the central nerve system or in the heart. Moreover, cancer stem cells have been described, which are important for the formation of tumors, especially in the human brain. EGFL7 might also be applied as a neuronal differentiation factor in ischemic insults or neurodegenerative diseases such as Alzheimer or Parkinson predict both researchers. Future work will unravel in which diseases EGFL7 can unfold its therapeutic potential. _Biosingularity

We are likely to find dozens of growth factors and differentiation factors that will come into play in the reversal of degenerative, traumatic, and age-related diseases of the brain. It will take time, investment, and long hours of dedicated research by an army of bright and well-trained researchers with open minds.

It is also important to eat the right foods, and to get plenty of exercise. Thinking "young" can also keep the brain more vital. Seek out new experiences and adventures. Try new foods, travel within your means, renew old friendships and make new ones.

It is easy to tell the difference between people who have given up, and those who will be scrapping right up to the end. Try to be a scrapper.

Will This Metallomolecule Help to Extend Life?

2009-06-09T10:21:00.000-07:00

Perhaps it will extend life. It can kill cancer, kill deadly resistant microbes, and may become a key part of the SENS anti-aging platform. Here is how:

The compound [Fe2L3]4+ is an iron triple helicate with three organic strands wrapped around two iron centres to give a helix which looks cylindrical in shape and neatly fits within the major groove of a DNA helix. It is about the same size as the parts of a protein that recognise and bind with particular sequences of DNA. The high positive charge of the compound enhances its ability to bind to DNA which is negatively charged.

When the iron-helicate binds to the major groove of DNA it coils the DNA so that it is no longer available to bind to anything else and is not able to drive biological or chemical processes. _PO

The interesting structure known as [Fe(2)L(3)](4+) was first researched as a treatment for cancer. But University of Warwick researchers have discovered that the metallomolecule is a particularly potent killer of bacteria -- even bacteria that are resistant to conventional antibiotics.

Initially the researchers focused on the application of this useful property for targeting the DNA of cancer cells as it could bind to, coil up and shut down the cancer cell's DNA either killing the cell or stopping it replicate. However the team quickly realised that it might also be a very clever way of targeting drug-resistant bacteria.

New research at the University of Warwick, led by Dr Adair Richards and Dr Albert Bolhuis, has now found that the [Fe2L3]4+ does indeed have a powerful effect on bacteria. When introduced to two test bacteria Bacillus subtilis and E. coli they found that it quickly bound to the bacteria's DNA and killed virtually every cell within two minutes of being introduced - though the concentration required for this is high. _PO

It will be important for the researchers to learn ways that the compound can be preferentially transported across bacterial membranes, to bacterial DNA. By reducing the necessary concentrations needed to kill the bacteria, and by making the construct preferentially attracted to pathological bacteria rather than to normal human cells, the safety and the efficacy of any possible future treatment using this compound will be enhanced.

The prevalence of antibiotic resistance has resulted in the need for new approaches to be developed to combat previously easily treatable infections. Here we investigated the potential of the synthetic metallomolecules [Fe(2)L(3)](4+) and [Cu(2)(L')(2)](2+) as antibacterial agents.... [Fe(2)L(3)](4+) binds in the major groove and causes DNA coiling... The work described here shows that ... [Fe(2)L(3)](4+) is bactericidal for Bacillus subtilis and Escherichia coli. We demonstrate that [Fe(2)L(3)](4+) binds bacterial DNA in vivo and, strikingly, that it kills B. subtilis cells very rapidly. _IntJnlAntimicrobialAgents

Cytocidal approaches are valuable medically to the extent they can be targeted and controlled -- with only limited damage to normal cells and tissues.

One of the main pillars of the SENS anti-aging approach is the elimination of superfluous and dangerous cells that have outlived their usefulness. The more precisely that one can target cytotoxic molecules, the more useful they will be for anti-aging therapies in addition to more conventional medical disciplines such as oncology and infectious disease.

Cross-posted at Al Fin

Regenerative Medicine Gets a Boost

2009-06-01T04:45:00.000-07:00

Blood disorders are likely to be the first targets for therapy because corrected cells can easily be transferred back to the patient via bone-marrow transplants. _TechnologyReview

Salk Institute researchers in La Jolla have demonstrated a technique that opens the door to cures for several genetic blood diseases. It involves taking a patient's skin cells, treating them genetically to correct the inherited disorder, next turning the skin cells into induced pluripotent stem cells (iPS), then differentiating those iPS into progenitor cells. These progenitor cells can be implanted into the patient to provide a supply of normal blood cells.

"This is an exciting bit of science," says Chris Mason, a professor of regenerative medicine at University College London, who was not directly involved in the research. "It's likely to be the first of a slew of similar papers that may offer hope for conditions where today there is no real therapy, let alone a cure."

So far, Belmonte's approach is applicable only to diseases in which the genetic defect that underlies the disease has been identified. "But there are quite a few of these--and the number will increase," says Mason. Blood disorders are likely to be the first targets for therapy because corrected cells can easily be transferred back to the patient via bone-marrow transplants.

Belmonte adds that in the future, the correction of more-complex genetic disorders might become possible, thereby significantly increasing the number of diseases that might be treated with altered iPS cells. _TechnologyReview

If the bone marrow can be "re-stocked" with viable normal blood progenitor cells, the inherited blood disorder may indeed be cured. The concept can be extended to other inherited and acquired genetic diseases with extensive work.

Such approaches to cell and tissue replacement open the door to significant extension of maximum life span.

Taken from an earlier post at Al Fin

Tiny Porous Nano-Spheres Carry 2 Drugs at Once

2009-05-30T07:25:00.001-07:00

Ames Lab researchers at Iowa State University continue their work with porous silica nano-spheres as drug delivery systems. This time, they have devised nano-systems capable of delivering two different drugs simultaneously.

A boronic acid-functionalized mesoporous silica nanoparticle-based drug delivery system (BA-MSN) for glucose-responsive controlled release of both insulin and cyclic adenosine monophosphate (cAMP) was synthesized. Fluorescein isothiocyanate-labeled, gluconic acid-modified insulin (FITC-G-Ins) proteins were immobilized on the exterior surface of BA-MSN and also served as caps to encapsulate cAMP molecules inside the mesopores of BA-MSN. The release of both G-Ins and cAMP was triggered by the introduction of saccharides. The selectivity of FITC-G-Ins release toward a series of carbohydrate triggers was determined to be fructose > glucose > other saccharides. The unique feature of this double-release system is that the decrease of FITC-G-Ins release with cycles can be balanced by the release of cAMP from mesopores of MSN, which is regulated by the gatekeeper effect of FITC-G-Ins. In vitro controlled release of cAMP was studied at two pH conditions (pH 7.4 and 8.5). Furthermore, the cytotoxicity of cAMP-loaded G-Ins-MSN with four different cell lines was investigated by cell viability and proliferation studies. The cellular uptake properties of cAMP-loaded FITC-BA-MSN with and without G-Ins capping were investigated by flow cytometry and fluorescence confocal microscopy. We envision that this glucose-responsive MSN-based double-release system could lead to a new generation of self-regulated insulin-releasing devices. _ACS

The ability to release two interacting substances from separate compartments in a nano-delivery system, provides for much longer shelf life and greater potency at the time of delivery. In this case, the payoff will be stop-gap implantable blood glucose regulation.

For long term control of diabetes, working cellular systems that can synthesise their own insulin are preferable to artificial systems. In general, the same principle is valid for all replacement organs and systems.

Replacement parts that can repair themselves, and work in concert with the rest of the body, are preferable to "one trick pony" replacements that too easily give out.

Almost certainly the best use of the Ames nano-spheres will be for genetic therapies to permanently alter gene expression of cells and tissues. But for now, proving the extent of functionality of this delivery system remains important.

50 Best Anti-Ageing Blogs

2009-05-26T15:55:00.000-07:00

The Ultrasound Technician Schools blog has put together a list of the 50 top anti-ageing blogs, for those who want to follow the broad range of online approaches to ageing and longevity.

Some of Al Fin's favourites that are on the list include Fight Aging, Ouroboros, and the Alliance for Aging Research.

Al Fin Longevity -- this blog -- finds itself on the top 50 list under the category of Longevity and Life Extension at #43.

As a side topic, I have noticed several healthcare training related blogs that provide wide ranges of lists of blogs for various topics. Some of these lists are quite useful. In fact, I would like to see a list of the top 100 list-making blogs. Wait -- what about a top 100 list of lists of top 100 list-making blogs? How about ..... Thwack!!

All righty then. My domestic android, Valerie, has just slapped me to bring me out of my list fugue. As Valerie points out, by the time you compiled the ultimate top 100 list of top 100 lists of lists of top 100 list-making blogs, the entire list would probably be obsolete. Please pardon me for the regression.

As scientific research pushes on, an extended lifespan becomes much more likely. The challenge will be not so much to keep living, but to combine the optimum mixture of enjoyable and important activities in order to fill one's life satisfactorily.

More important than improving the quantity of life is improving the quality of life. But doing both at the same time beats either one alone.

A Better Matrix for Artificial Tissues and Organs?

2009-05-18T07:59:00.000-07:00

One of the challenges of creating artificial organs for replacement of human body parts is the need for a structural matrix to build the functional tissue around. Australian and Korean scientists have developed an interesting approach to the problem by pairing carbon nanotubes and DNA strands together, then treating them with calcium chloride solution to create cross-linking between the fibres.

The new concept uses DNA strands as a matrix; the strands completely “wrap” the scaffold-forming carbon nanotubes in the presence of an ionic liquid, networking them to form a gel. This gel can be spun: just as silk and synthetic fibers can be wet-spun for textiles, the gel can be made into very fine threads when injected into a special bath. The dried fibers have a porous, sponge-like structure and consist of a network of intertwined 50 nm-wide nanofibers. Soaking in a calcium chloride solution further cross-links the DNA, causing the fibers to become denser and more strongly connected.

These spongy fibers resemble the collagen fiber networks of the biological extracellular matrix. They can also be knotted, braided, or woven into textile-like structures. This results in materials that are as elastic as the softest natural tissues while simultaneously deriving great strength from the robust DNA links. An additional advantage is the electrical conductivity of the new material, which can thus also be used in electrodes for mechanical actuators, energy storage, and sensors. _Wiley

A similar matrix might be seeded with living cells to create tendons, cartilage, or more complex structures such as noses, ears, blood vessels, eyelids, lips, or as support reinforcement for hernia or breast surgeries etc. Reconstructive surgery and vascular surgery would create a demand for such living replacement parts immediately, should they prove safe and durable.

For more complex organs such as kidneys, livers, lungs, and hearts, more breakthroughs will be needed. For intermediate structures such as bladders, rectums, and other GI or GU segments, the jump from simple replacement parts may not be too difficult once the best ways for making the simpler parts are perfected.

Previously posted at Al Fin The Next Level

Tiny Nerve Stimulator Implants Use RFID Tech

2009-05-15T15:20:00.000-07:00

These tiny implantable nerve stimulators are meant to stimulate peripheral nerves to treat chronic pain and other neurological disorders. But eventually, devices this small -- or smaller -- will fit near or within the brain, to deliver tiny currents of healing and eventually pleasure.

Like some cochlear implants and other medical devices, the implant is powered with radio-frequency transmission: radio waves transmitted by the external coil generate a magnetic field in the internal coil, which powers the electrodes. Adopting technologies from the rapidly advancing RFID world has allowed the researchers to further shrink the device. "Instead of trying to transfer energy from two coupled antennas to do telemetry, which is a common approach for medical devices, RFID is geared to have very small transponders, so you don't need a large coil," says Joseph Pancrazio, a program director at the National Institute for Neurological Disorders and Stroke, a government funding agency, in Bethesda, MD, that has given the company small business loans.

The research is still in a very early stage. Researchers have developed a prototype device, which they are testing in rats. The device can effectively stimulate peripheral nerves in rats, although it's not yet clear whether the electrical stimulation alleviates chronic pain. (Scientists assess chronic pain in rats by recording how much the animals eat; a rat in pain won't eat as much.)

Some scientists are skeptical that the device will be powerful enough to deliver a therapeutic level of stimulation. "The main limitation of any electronic device small enough to be injected into the body is that it must receive enough power to operate its circuitry and provide the required stimulation parameters," says Gerald Loeb, director of the Medical Device Development Facility at the University of Southern California, in Los Angeles. Loeb has also developed an injectable radio-powered microstimulator, which he says has encountered substantial limitations in range and power.

"We believe we can do it with less power," says Scott Armstrong, MicroTransponder's chief technical officer. However, he declined to give further details of the technology for proprietary reasons. _TechnologyReview

If not now, soon. It is quite clever of the researchers to use RFID technology for implantable nerve stimulators. Such an approach could be easily transferred to intracranial implants-without-antennas, as long as the power signal was able to safely penetrate the skull without damaging intervening tissues. Otherwise, antennas that are colour-matched to the person's hair could transmit the power signal to the implant. Advances in biocompatible materials will make such long-term implants viable.

Needless to say, technology that allows for miniaturisation of implants should also allow for simultaneous placement of multiple, strategically-placed implants that could communicate with each other, and coordinate for sophisticated neuro-stim routines.

Cross-posted at Al Fin

Restoring Lost Memories to Dementia Sufferers

2009-04-21T05:47:00.001-07:00

When a person has a loved one with dementia, it is as if part of themselves is lost. Shared memories between pairs and groups of humans is a large part of what makes life satisfying and fun. When shared memories are lost, life's colours can fade. Researchers at MIT are attempting to understand the molecules of memory better, in order to restore lost memories to persons who suffer from dementia.

Having shed light on the mechanisms driving the progress of Alzheimer's disease, Tsai, who had come to MIT in 2006, wanted to figure out how to fight or even reverse some of the symptoms. She and postdoc Andre Fischer, now at the European Neuroscience Institute in Göttingen, Germany, knew of evidence from other studies that physical exercise and environmental enrichment--such as the addition of companions and toys--increases brain function in mice. So they decided to test what would happen if they tried this technique with their Alzheimer's-like mice.

In one experiment, they trained mice to find and remember a platform submerged within a murky pool. Then they induced the Alzheimer's-like effects. The mice swam aimlessly, unable to locate the spot. But when the researchers moved the mice to a more stimulating environment and then placed them back in the swimming pool, the rodents kicked directly to the platform. Those supposedly lost memories had returned.

....The results imply that restoring seemingly lost memories might also be possible in people. "Even in those patients that seem to lose their memory, we don't think the memory is really erased," she says. Tsai suspects that the massive neuronal die-off damages the brain's circuitry--the wiring that connects different regions. Rather than promoting neuron growth, she says, the new environment and the HDAC inhibitors strengthen synapses and dendrites, boosting connections between regions. In other words, they repair the circuits.

...."We're very hopeful," she says. "We may have something in the next few years that could be safe and beneficial enough to go into humans." Basic research may remain her first love, she adds. "But if my work can do something for the community or society, I would be so overjoyed." _TechnologyReview

We value most the things we can share.

If you don't have your mind, you have nothing. If you have your mind but not your health, at least you have your mind. Better to have your mind and your health, of course. Best of all, to be able to share good minds and good health with others of similar good fortune. A fulfilling life is a step by step proposition. Too often, the natural processes of life work against all of our efforts to create a fulfilling life. That is where we ask science to step in. It is not natural, what we are trying to do. But it is good.

Australian and American Researchers Team to Advance Regenerative Medicine Strategies

2009-04-07T10:52:00.000-07:00

When humans can grow new organs to replace tired or damaged organs, we will transcend one of the reasons for too-early death: organ failure. Every advance in the field of regenerative medicine is a positive step toward that goal.

John Foster's Bio/Polymer Research Group at the University of NSW worked out in 2004 the correct wavelength of infra-red laser to seal sheets of the university's patented discovery, SurgiLux, over wounds.

Now Foster is teaming up with Stephen Badylak, pioneer of the extra-cellular matrix, at the McGowan Institute for Regenerative Medicine at the University of Pittsburgh. Badylak creates ECM from ground-up pig organs. It acts as a scaffolding material for wounds and can be absorbed by the body. Cells spontaneously regrow on it and adult stem cells are attracted from other parts of the body, developing into tissue similar to the original.

These scaffolds have helped more than one million people regrow cartilage, rebuild urethras and repair hernias.

Foster and Badylak hold high hopes for the marriage of their technologies now that Foster has been awarded aFulbright senior scholarship that will fund him for up to four months' work with Badylak's group from June next year. The aim is to develop the technology to support the surgical repair ofnerves. _Australian

Growing new cells and tissues in the proper mix of cell types with neurovascular and lymphatic support, will require precise methods and timing. Learning how to best attach the new cells, tissues, and organs to the rest of the body is a vital part of the regenerative picture.

Gamma Secretase Inhibitors: Meant for Alzheimer's but Also Helpful for Brain Trauma?

2009-03-17T06:16:00.000-07:00

Georgetown University scientists have studied the use of gamma secretase inhibitors (GSIs) to prevent permanent brain injury after head trauma, in mice. GSIs prevent the formation of amyloid buildup in the brain, in order to prevent or mitigate the amyloid plaques of Alzheimer's disease.

Interestingly, amyloid also accumulates in the brains of persons with brain injuries -- even very young victims of head injury.

Researchers at Georgetown University Medical Center will publish their findings in an advance online publication of Nature Medicine.

They say the results suggest that this class of drugs could potentially do something no other drug has been able to do — prevent the long-term and continuing damage that often follows a serious injury to the brain.

That is because the agents, known as gamma secretase inhibitors, are designed to prevent buildup of amyloid, a toxic peptide found in the brain. This peptide clogs the brains of Alzheimer’s patients but it is also found in people who have died from traumatic brain injury, says the study’s lead author, neuroscientist Mark Burns, Ph.D, an assistant professor at GUMC.

“No one knows why it occurs, but abnormal amounts of amyloid plaque have been found during an autopsy in about a third of brain injury victims, some of whom were children who would ordinarily never have had these deposits,” says Burns. _PsychCentral

Amyloid deposits can begin building as soon as 1 day after injury -- demonstrating how dynamic a contribution amyloid may make to long term brain damage.

It is hoped that rapid diminution of amyloid deposits will lead to brain recovery in both Alzheimer's patients and in victims of traumatic brain injury. For mice, the treatment was successful in blocking permanent brain damage.

GSIs are currently investigational drugs. If they can demonstrate efficacy for both Alzheimer's and traumatic brain injury, clinicians can hope for a dual approval when the drugs are released.

Turbocharging Antibody Response to Cancer etc

2009-03-11T10:33:00.000-07:00

The human immune system is a powerful deterrent to a wide range of diseases, including cancer. But it takes time to build an immunity to new diseases. Researchers at Scripps Research Institute have devised a synthetic adaptor that can generate an almost instant immune response to the protein target of one's choice.

Most vaccines - like those for measles or smallpox - prompt the immune system to build a standing army of antibodies against a virus or bacterium by injecting a deactivated version of the bug into the body.

But it can take weeks or months to build up immunity, and you have to catch people before they get infected. What's more, the approach doesn't always work - cancer and HIV vaccines have proved elusive.

So instead, Carlos Barbas and colleagues at the Scripps Research Institute in La Jolla, California, have developed dumb-bell shaped "adaptor" molecules that bind mouse antibodies to proteins on the surface of disease-causing agents, redirecting the antibodies' killing focus. In an earlier experiment they attached these molecules to a single kind of antibody in the lab, and injected these "retrofitted" antibodies into the mouse to kill tumour cells.

Now they have demonstrated that these synthetic molecules can bind many kinds of antibodies to cancer cells inside mice and reduce the size of implanted human tumours.

Four weeks after the molecules were injected, the colon tumours had shrunk by up to 90 per cent, and melanomas by 78 per cent (Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.0900147106). _NS

Even if this new immune therapy does not completely eradicate a tumour, by shrinking its size it gives the patient's medical team more time to chance upon the magic bullet treatment for that particular patient. Each person is different, so it is natural that a person's response to disease and therapy will be unique.

A Realistic Look at Obama's Stem Cell Order

2009-03-10T10:11:00.000-07:00

President Obama's long anticipated and much heralded signing of new federal guidelines for the financing of embryonic stem cell research will help US scientists learn more of the mysteries of embryonic cell differentiation and manipulation. But in reality, the effect of the new rules will be far less significant for the future of regenerative medicine than most gullible news consumers will ever know.

.....the president’s support of embryonic stem cell research comes at a time when many advances have been made with other sorts of stem cells. The Japanese biologist Shinya Yamanaka found in 2007 that adult cells could be reprogrammed to an embryonic state with surprising ease. This technology “may eventually eclipse the embryonic stem cell lines for therapeutic as well as diagnostics applications,” Dr. Kriegstein said. For researchers, reprogramming an adult cell can be much more convenient, and there have never been any restrictions on working with adult stem cells.

For therapy, far off as that is, treating patients with their own cells would avoid the problem of immune rejection.

Members of Congress and advocates for fighting diseases have long spoken of human embryonic stem cell research as if it were a sure avenue to quick cures for intractable afflictions. Scientists have not publicly objected to such high-flown hopes, which have helped fuel new sources of grant money like the $3 billion initiative in California for stem cell research.

In private, however, many researchers have projected much more modest goals for embryonic stem cells. Their chief interest is to derive embryonic stem cell lines from patients with specific diseases, and by tracking the cells in the test tube to develop basic knowledge about how the disease develops.

Despite an F.D.A.-approved safety test of embryonic stem cells in spinal cord injury that the Geron Corporation began in January, many scientists believe that putting stem-cell-derived tissues into patients lies a long way off. Embryonic stem cells have their drawbacks. They cause tumors, and the adult cells derived from them may be rejected by the patient’s immune system. Furthermore, whatever disease process caused the patients’ tissue cells to die is likely to kill introduced cells as well. All these problems may be solvable, but so far none have been solved.

Restrictions on embryonic stem cell research originated with Congress, which, each year since in 1996, has forbidden the use of federal financing for any experiment in which a human embryo is destroyed. This includes the derivation of human stem cell lines from surplus fertility clinic embryos, first achieved by Dr. James Thomson of the University of Wisconsin in 1998.

President Clinton contemplated but never implemented a policy that would have allowed N.I.H.-financed researchers to study human embryonic stem cells derived by others. Research was able to begin only in August 2001, when President Bush, seeking a different way around the Congressional restriction, said researchers could use any lines established before that date.

Critics said the distinction between the Clinton and Bush policies lacked moral significance, given that each was intended to get around the Congressional ban, based on a religious and moral argument. The proposed Clinton policy amounted to: “Stealing is wrong, but it’s O.K. to use stolen property if someone else stole it.” The Bush policy was: “Stealing is wrong, but it’s O.K. to use stolen property if it was stolen before Aug. 9, 2001.”

Mr. Obama has put the proposed Clinton policy into effect, but Congressional restrictions remain. Researchers are still forbidden to use federal financing to derive new human embryonic stem cell lines. They will, however, be allowed to do research on new stem cell lines grown in a privately financed lab. _NYT

More research on embryonic stem cells will help scientists understand the intricate mechanisms of cell development. They will acquire a fabulous treasure trove of knowledge about many diseases -- both rare and less rare. The knowledge spinoffs from this research will stretch far beyond regenerative medicine (RM) to cancer treatments, life extension technologies other than RM, and a much deeper understanding of biological mechanisms in general.

But all of that would have occurred without that much celebrated penstroke yesterday. And it is undeniable that the flow of NIH funds to non-embryonic stem cell research has been a boon to technologies that are more immediately applicable to the everyday regenerative cell and tissue treatments of the future -- treatment using the patient's own cells.

Science under Obama is every bit as political as science under any other president -- and will probably only grow more political with time. Obama's promotion of carbon penalties (disguised as "cap and trade") are a politicised hyping of the pseudo science of catastrophic global warming from anthropogenic CO2. Obama's carbon hysteria-based political meddling in the energy industry is likely to make Americans far more miserable, leaving them with far less resources to deal with exigencies, than if he had done nothing at all.

So let's celebrate the abundant biological future that will eventually come to us via all the avenues of research being followed. And let us not fall for the hype surrounding the gilded age of Obamanation.

Taken from an earlier posting at Al Fin

More Engineered Stem Cell News

2009-03-01T13:41:00.000-08:00

Toronto's Samuel Lunenfeld Research Institute at Mt. Sinai Hospital is the site of groundbreaking research on engineered stem cells.

"We hope that these stem cells will form the basis for treatment for many diseases and conditions that are currently considered incurable," said Dr. Nagy, Senior Investigator at the Samuel Lunenfeld Research Institute of Mount Sinai Hospital, Investigator at the McEwen Centre for Regenerative Medicine, and Canada Research Chair in Stem Cells and Regeneration. "This new method of generating stem cells does not require embryos as starting points and could be used to generate cells from many adult tissues such as a patient's own skin cells."

Dr. Nagy discovered a new method to create pluripotent stem cells (cells that can develop into most other cell types) without disrupting healthy genes. Dr. Nagy's method uses a novel wrapping procedure to deliver specific genes to reprogram cells into stem cells. Previous approaches required the use of viruses to deliver the required genes, a method that carries the risk of damaging the DNA. Dr. Nagy's method does not require viruses, and so overcomes a major hurdle for the future of safe, personalized stem cell therapies in humans.

"This research is a huge step forward on the path to new stem cell-based therapies and indicates that researchers at the Lunenfeld are at the leading edge of regenerative medicine," said Dr. Jim Woodgett, Director of Research for the Samuel Lunenfeld Research Institute of Mount Sinai Hospital. Regenerative medicine refers to enabling the human body to repair, replace, restore and regenerate its own damaged or diseased cells, tissues and organs. _PO

The new method avoids the risks of tumourogenesis that come with using viruses for reprogramming cells into stem cells. Various new and potent techniques of producing virtually any stem cell type from adult cells bring modern biomedicine ever closer to the ability to replace and / or rejuvenate virtually any tissues in the body -- using the person's own cells!

There is still much to be learned about the genetic switching mechanisms involved. Until we are certain that the re-programming techniques can truly provide safe, long-lived replacement cells for the various tissues of the body, we will need to continue experimenting with embryonic stem cell lines as well as with the re-programmed stem cells.

New Alzheimer's Disease Model Offers Hope for a New Array of Therapeutic Targets

2009-02-20T10:15:00.000-08:00

Biomedical research is learning a great deal about how the brain works at the cellular level. Alzheimer's Disease, for example, is being seen more as an imbalance within normal cell processes -- like cancer. A better understanding of these processes should allow more precise targeting of drug research.

One of the mysteries of AD has been the normal function of the amyloid precursor protein (APP) which are concentrated at the points where neurons connect. Even though the sticky amyloid plaques which have been viewed as a hallmark sign of AD result from APP, it seems unlikely that APP exists simply to cause Alzheimer's disease. In their study, scientists from the Buck Institute and the CNRS (Centre Nationale de la Recherche Scientifique) show that APP binds to netrin-1, a protein that helps to guide nerves and their connections in the brain, as well as helping nerve cells to survive. When netrin-1 was given to mice that have a gene for Alzheimer's disease their symptoms were reversed, and the sticky amyloid was reduced. These results suggest that the long-held belief that AD is caused by brain cell damage inflicted by the amyloid plaques may be wrong; instead, it is beginning to appear that the disease stems from an imbalance between the normal making and breaking of connections in the brain, with netrin-1 supporting the connections and the amyloid breaking the connections -- both by binding to APP and activating normal cell programs. Not only did the netrin-1 binding to APP keep the nerve cells alive and connected, but it also shut down the production of the amyloid, all of which makes it an interesting potential therapeutic. _Scientistlive

In the past few decades, the therapeutic viewpoint toward Alzheimer's has paced the rapidly growing knowledge of the underlying mechanisms of the disease. Already we have gone through multiple generations of treatments, with several radically new treatments in the pipeline. If "netrin-1" or its analogues can be delivered to the proper brain regions, and can at least partially reverse both the histological and the clinical pathology in AD, we will not only have a better treatment, but we will have one more promising lead to follow.

New Stem Cell Hope For Parkinson's

2009-02-17T09:16:00.000-08:00

Researchers in Bonn have developed a method of culturing an indefinite supply of replacement neural stem cells -- including the cells that fail in Parkinson's -- from a single embryonic source.

"The new cells, in contrast, serve as an inexhaustible source: they provide a supply of human neural cells over periods of months and years without demanding any recourse to supplementary embryonic stem cells", declares Professor Dr. Oliver Brüstle, head of the research team at the Institute for Reconstructive Neurobiology at Bonn University.

Using animal experiments, the researchers in Bonn provided direct proof that these artificially derived neural cells will also function. Transplanted into the brain of a mouse, these cells made contact with the recipient brain and were subsequently able both to send and receive signals. "This is the first direct evidence that neural cells derived from human stem cells are capable of synaptic integration in the brain", declares Dr. Philipp Koch, the original author of the study. The scientists in Bonn are now also hoping to exploit this inexhaustible cell source to study neurodegenerative diseases and possible active agents directly in human neural cells. _MNT

If scientists can prevent the rejection of donor stem cells, the pathway toward routine replacement of aging brain tissue is now being constructed. Adult induced pluripotent stem cells from the patient herself is the best means for preventing rejection of tissue and stem cell implants. But if embryonic cell and tissue banks are able to carry a large "on-demand" supply of suitable cells, they will be quite useful.

Clearly the promise of stem cell research applies to other diseases besides Parkinson's, and to other organs besides the brain.

The problem for the US -- where funding for the development of new embryonic stem cell lines is expected to be expanded -- is the overall economy. The new government appears not to understand how a market economy recovers from a recession -- a recession that was brought on by bad government policies to begin with. A helpful hint to Obama and Pelosi: get rid of those bad government policies! (CRA etc)

Interferon Makes Dormant Cells Vulnerable

2009-02-14T07:10:00.000-08:00

Dormancy is an important protection mechanism of stem cells. First, it protects their genetic material from genetic alterations, which happen primarily during cell division. In addition, dormancy helps them escape attacks of many cytotoxins, which act only on dividing cells. _MNT

Many cancer stem cells are likewise dormant, which can protect them from chemotherapy. Waking these cancer stem cells up before chemotherapy is one way to kill more of them, and increasing chances for a remission. Interferon seems to wake stem cells up from a dormant state, and force them to divide. This makes them vulnerable to mutation and to cytotoxins.

Patients suffering from a type of blood cancer called chronic myelogenous leukemia who are treated with a drug called Gleevec almost always relapse after drug treatment has ended. Several patients were given interferon-alpha prior to the Gleevec treatment. Surprisingly, these patients experienced long relapse-free phases without any medication. "We believe that the leukemia stem cells were awakened by the interferon administration and, thus, were sensitized to elimination by Gleevec," Andreas Trumpp explains. _MNT

The other side of the story is that interferon makes normal stem cells vulnerable to cytotoxic agents, so that blood forming stem cells in the bone marrow will be killed by some chemotherapeutic agents such as 5-FU, if interferon is given first. This can cause severe anemia and death.

This knowledge can lead one to speculate about the effects of viral infections and natural interferon on stem cells in other locations, such as the brain. The constant infectious assault experienced in the tropics, for example, may lead to chronic depletion of stem cells with all of the failure of normal regeneration that such depletion implies.

Each scientific discovery becomes the trigger for new exploration. The contemporary human mind cannot keep up with the multiple ongoing chain reactions of knowledge, but computers should be of some help.

Skin Cells Programmed to Become Heart Cells

2009-02-12T18:11:00.000-08:00

Using techniques of induced pluripotent stem cell conversion, scientists at the University of Wisconsin created heart cells out of skin cells. The idea is to take a person with heart failure, make functioning replacement heart cells from abundant skin cells, and give the person what is in essence a new heart.

"This is the first demonstration that human induced cells can form different types of heart cells in a dish," said study co-author Tim Kamp, a University of Wisconsin cell biologist.

The latest findings, published Thursday in Circulation Research, suggests that failing hearts might be mended.

"We didn't know whether they could form heart cells efficiently," said Kamp. "But they successfully formed heart cells with all the electrical and organizational properties we'd expect."

In the last few years, induced pluripotency has been hailed as an uncontroversial alternative to embryonic stem cells, production of which requires the destruction of embryos.

Reprogramming flakes of skin would be a far easier alternative. _Wired

Novel Alzheimer's Drugs Coming

2009-02-11T09:44:00.000-08:00

• As many as 5.2 million people in the United States are living with Alzheimer’s.

• 10 million baby boomers will develop Alzheimer's in their lifetime.

• Every 71 seconds, someone develops Alzheimer’s.

• Alzheimer's is the sixth-leading cause of death.

• The direct and indirect costs of Alzheimer's and other dementias to Medicare, Medicaid and businesses amount to more than $148 billion each year. _Alz

The older you get, the more likely that you will suffer some form of cognitive impairment -- most likely Alzheimer's. With the aging of North America and the developed world, the need for better ways to diagnose and treat Alzheimer's is critical.

New cognitive tests are being developed to determine whether a person with early cognitive impairment can drive safely. Special MRI techniques can show the early tell-tale signs of Alzheimer brain atrophy.

On the treatment side, "brain games" that develop short term memory appear helpful in reversing early cognitive impairment.

Another hopeful bit of news is that Rember and Dimebon -- two novel drug treatments for Alzheimer's -- are working their way through human drug trials, and show some promise.

A bit further in the future is the promise of Ampakines. Cortex Pharmaceuticals is the foremost developers of Ampakines for a wide range of disorders -- including Alzheimer's in the long run.

Further into the future, an even wider array of drugs are being developed to target several pathological mechanisms that are believed to contribute to Alzheimer's.

The main question at this time appears to involve financing for drug discovery and testing in the midst of an international financial crisis. US governmental policies under the new administration suggest that US pharmaceutical research and research into other vital innovative technologies will be short-changed. New drug development may well move offshore from the US to East and South Asia, where capital is less likely to be diverted to non-productive ends.

It is ironic that just when a relaxation of stem cell research regulations occurs, that draconian economic re-structuring should threaten the future of technological development in the biosciences and most other high tech fields.

Genetically Modified Regenerative Skin Graft Material Designed to Resist Infection

2009-02-03T15:28:00.000-08:00

Stratatech’s StrataGraft® tissue is a second-generation human skin substitute that exhibits normal human skin structure and function. It is manufactured using the company’s proprietary NIKS® human keratinocytes, which were discovered at the University of Wisconsin. Keratinocytes are the cells that make up approximately 90 percent of the epidermis, the outer layer of human skin. NIKS® cells are a consistent source of pathogen-free, non-tumor-producing, long-lived adult progenitor cells. These cells faithfully reproduce normal human skin tissue architecture and barrier function when cultured appropriately. _StratatechCorp.

Regenerative medicine company Stratatech Corporation has developed a genetically tweaked living skin substitute for use in skin grafting. The genetic modifications of the living skin replacement makes it far more resistant to infection than currently available skin graft materials -- including autologous skin grafts.

The anti-infective capacity of Stratatech’s genetically-engineered tissue, which is being developed and commercialized by the company as ExpressGraft™ Enhance skin substitute through a worldwide exclusive license from the Wisconsin Alumni Research Foundation, or WARF, is produced by genetically engineering the elevated expression of a naturally-occurring antimicrobial host defense peptide called hCAP-18/LL-37. hCAP-18/LL-37 was selected because of its broad antimicrobial activity against both Gram-positive and Gram-negative bacteria, including methicillin-resistant S. aureus (MRSA), vancomycin-resistant E. faecalis (VRE) and other antibiotic-resistant hospital-acquired infections, as well as some fungi and viruses. The enhanced tissue possesses a full-thickness structure and barrier function similar to that of native human skin. The cell type used to generate the ExpressGraft™ tissue has been demonstrated to be non-tumor-producing and free from detectable pathogens, characteristics critical for cell-based, regenerative medicine therapies for patient use.

“Bacterial infection is a substantial cause of skin graft rejection and additional health care costs,” said Lynn Allen-Hoffmann, Ph.D., Stratatech’s founder, chief scientific officer and chief executive. “The potent anti-infective capability Stratatech has engineered in our living human skin substitute can be an important tool in improving skin-injury patient outcomes, and reducing the incidence and expense of hospital-acquired infections. We look forward to beginning the clinical evaluation of our antimicrobial skin substitute in the near term.

...Stratatech’s genetically-engineered skin substitute was generated using a non-viral vector, or carrier. The company believes it is the first time a virus-free approach has been used to genetically modify a living, cell-based tissue substitute. The data published in Molecular Therapy demonstrate that the modified tissue contained 139-fold more anti-infective proteins called host defense peptides than unmodified tissue in vitro. _BusinessWire

This is only the beginning of genetically improved, artificially grown bio-replacement materials. This skin replacement product from Stratatech should do well in the marketplace if it lives up to its promotion. But expect competing products that improve on the ExpressGraft's performance to emerge before long. This graft material does not perfectly reproduce the full, intricate layered structure of natural skin. But it is a good start.

Other more intricately structured grown replacement parts should follow on rather quickly. We are entering the age of regenerative medicine, when body parts and tissues will be grown in labs, rather than being donated by accident and crime victims. If these replacements can be designed to be tougher than the original parts being replaced, all the better.

Not Over the Hill Yet, Baby!

2009-01-30T16:49:00.000-08:00

From the journal Stem Cells: UCLA researchers have managed to program human induced pluripotent stem cells into the precursors of human reproductive cells -- eggs and sperm. As quoted in Biosingularity:

Theoretically, an infertile patient’s skin cells, for example, could be taken and reprogrammed into iPS cells, which, like embryonic stem cells, have the ability to become every cell type in the human body. Those cells could then be transformed into germ line precursor cells that would eventually become eggs and sperm. Clark cautioned, however, that scientists are still many years from using these cells in patients to treat infertility. There is still much to be learned about the process of making high quality germ cells in the lab.

In another important finding, Clark’s team discovered that the germ line cells generated from human iPS cells were not the same as the germ line cells derived from human embryonic stem cells. Certain vital regulatory processes were not performed correctly in the human iPS derived germ cells, said Clark, an assistant professor of molecular, cell and developmental biology.

So it’s crucial, Clark contends, that work continue on the more controversial human embryonic stem cells that come from donated, excess material from in vitro fertilization that would otherwise be destroyed.

When germ cells are formed, they need to undergo a specific series of biological processes, an essential one being the regulation of imprinted genes. This is required for the germ cells to function correctly. If these processes are not performed the resulting eggs or sperm, are at high risk for not working as they should. This has significant consequences, given that the desired outcome is a healthy child. _Biosingularity

In other words, women past menopause or who have had their ovaries removed and men without testicles or with very low sperm counts will soon be able to produce viable sperm and eggs with the best of the twenty-somethings! Yes, I know that most people of a certain age do not want to have more children. But modern women often pursue their careers through the ages of optimal reproduction, and find that it's too late to have children by the time they feel they are ready. There are many other situations where persons might want to have their own children but can no longer produce the germ cells to do the job.

Eventually we will have artificial wombs that will take early embryos and support healthy gestation all the way to birth. By then, most of us will probably be living in good condition to 150 or beyond. Some may live long enough to raise three generations of offspring to adulthood. Why not, if you enjoy it and you can do it well?

Because by then, the question will not be "where will we put all these people?" The question will be, " where will we ever get enough people to do all the things that need to be done in this big universe?"

New Drug Class Promises a Medical Revolution

2009-01-26T09:23:00.000-08:00

Image Source

Research into the effects of melanocortins has a huge potential to revolutionise medicine. Here are a few of the effects of melanocortin peptides on the brain:

Increase of motivation
Increase of attention
Improvement of short-term memory
Increase of visual retention
Lowering of auditory, gustatory and olfactory detection thresholds
Functional antagonism of opiate effects
Inhibition of feeding (satiety-inducing effect)
Antiinflammatory effect (sites of action: brain and immunocytes)
Antipyretic effect
Reversal of hypovolemic hypotension
Reversal of shock
Resuscitation after prolonged asphyxia
Improvement of recovery after traumatic brain lesions and spinal cord injuries
Delay of the aging-linked behavioural deficits
Beneficial influences in neurodegenerative disorders
Increase of regenerative capacity of peripheral nerves in postlesion repair
Improvement of diabetic and toxic neuropathies
Induction of spontaneous penile erections
Increase of [sexual] proceptivity and receptivity (in females)

_Pharmacological Research

Like I say, those are a few of the effects that have been discovered so far for the melanocortins (melanocyte stimulating hormones [MSH], ACTH). New drugs which can either block or stimulate these hormone receptors will likely revolutionise treatment for:

Alzheimer's and other neurodegenerative disease
Stroke
Diabetic Neuropathy
Hemorrhagic Shock
Sexual Dysfunction for males and females
Obesity
Anorexia and Cachexia
Depression
Anxiety
Various learning disorders

...and quite a few things more. It is only in the past decades that scientists have been able to distinguish different receptor types for the many peptides and neurotransmitters affecting the brain and nerves. Now, it looks like nothing can stop the steamroller of biomedical and biotech research -- except perhaps bad government that wastes precious resources on policies that have failed for many generations.

If you have an interest in any of the listed diseases or hormonal effects above, visit the linked article and skip down to the section that interests you particularly. It is a long review article that covers a wide range of effects and potential therapies. I strongly recommend learning to read scientific articles -- despite their dryness -- because any person who can draw meaning from the early stages of research can often see into the future, and profit from that vision. If you wait until "science journalists" spell it out and dumb it down for you, it may be too late.

When the baby revolutions of nanotechnology, biotechnology, information sciences, and cognitive sciences begin to grow up and converge, you will begin to understand how quickly things can change.

From al fin

Constructing New Infrastructure for Regeneration

2009-01-22T16:09:00.000-08:00

Tissue scaffolds are the next big thing for implants of the future. Like the scaffolding we see on construction sites, the nano scaffolds are being created by Ko to reconstruct damaged tissue within the human body. Burn victims would benefit from scaffolds used to regenerate new skin. Those with failing heart valves or damaged nerves could count on scaffolds to regenerate these parts from within the patient’s own body. As healing progresses, the scaffold, being constructed from a biodegradable material, is absorbed and metabolized by the body while slowly releasing drugs to aid in the healing process. _CyborgAge

Almost every part of the body presents opportunities for scaffold bio-engineers to experiment. From the heart to the spine to the skin, all parts of the body eventually wear out and need to be replaced or regenerated. Scientists at UC Berkeley are taking an entirely new approach to bio-scaffold development. They are using viruses (bacteriophages) to build a proteinaceous infrastructure that promotes regeneration of nerve tissue.

Some biological engineers are using scaffolds made of polymers to try to mimic the supportive matrix of real tissue. Seung-Wuk Lee, a bioengineer at the University of California, Berkeley, has turned to viruses instead. "Viruses are smart materials," he says. "Once you construct the genome, you can make billions of phages, and they're self-replicating materials." The phage that Lee is working with, called M13, is long and thin like the protein fibers that make up the cellular matrices inside the body.

First, Lee and his colleague Anna Merzlyak genetically engineered M13 to display nerve-friendly proteins on their outer coats. These proteins are known to help nerve cells proliferate, adhere, and extend into long fiberlike shapes. Next, the researchers grew large numbers of the viruses in bacterial-cell hosts and dropped them into a solution containing neural-progenitor cells. These cells are more fully developed than stem cells but are still young and need coaxing to form new tissues. In the solution, the viruses align themselves like a liquid crystal, says Lee. He and Merzlyak used pipettes to inject the solution into agar, a Jell-O-like cell-culture medium, creating long, nerve-like fibers of the virus interspersed with cells. The progenitor cells then multiplied and grew the long branches characteristic of neurons. Lee says that the phage are well suited to making long, fiberlike structures such as nerve tissue but can also be made into more complex structures by varying their concentration or manipulating their position with a magnetic field. _TechnologyReview

Lee is planning to move to research inside live animals next. He is interested to discover how the immune systems of animals will react to viral construction workers hammering, drilling, and welding new infrastructure deep inside the organism.

For regenerative medicine to take that next big step forward, it will need the ability to grow specific infrastructure for every tissue and organ type that will be replaced or regenerated. Then, scientists will need to integrate growth factors and stem cells into the new matrix, and provide optimal nutrient solution. The prognosis for significant progress in this area is extremely favourable.

Nerve Regeneration Gene Pathway Discovered

2009-01-22T14:34:00.000-08:00

Image Source

Research at the University of Utah has pinpointed specific genes in worms that appear to trigger nerve re-generation, and make old worms behave like younger friskier worms when the genes are over-expressed.

"One of the coolest things is we can improve regeneration," Nix says. "We originally looked at loss of this gene, dlk-1. The loss blocks regeneration. We can cut the nerve in these mutants and they don't regenerate. So we see worms with nerve stumps that don't do anything. But when we overproduce dlk-1 make an excess amount of it then we see an improvement in regeneration."

Jorgensen an investigator with the Howard Hughes Medical Institute says that "normally, young worms regenerate really well; old worms don't regenerate at all. What we can do by overexpressing dlk-1 is make old worms regenerate like young worms."

The chain of events the researchers identified as playing an essential role in nerve regeneration is known as a "MAP kinase pathway." Various MAP kinases play roles in cell division, response to stress, and cell specialization, Jorgensen says.

The pathway discovered in the new study "is unique in that it is not used by the nervous system during normal embryo development, yet it is absolutely required for regeneration," Bastiani says. "Most of us believed that virtually everything we found in regeneration also would be involved in development. So it is surprising."

He says while the dlk-1 gene is the most obvious target for new drugs to stimulate nerve regeneration, other genes in the pathway also could be potential targets. _GEN

Humans possess the same sets of genes that were studied in worms. It remains to be proven whether the genes have the same effect in humans for nerve regeneration, as in worms.

We are finding that older cells become leaky and let more damaging substances into their nuclear compartments, where DNA becomes damaged. Better means of preventing nerve damage and reversing that damage are beginning to come within the grasp of science.

Optical Coherence Tomography Provides an Active Window on the Brain

2009-01-18T11:14:00.000-08:00

Optical Coherence Tomography (OCT) is a powerful new tool for monitoring both degenerative and malignant activities occurring deep within the brain -- by looking into the eyes. The OCT scanner uses two light beams (diodes or pulse lasers) to generate a 3d image of the depth of the retinas. This information tells medical specialists many different things about what is happening inside the skull.

One beam of light is fired at the tissue and another at a reference mirror. When the reflected beams have travelled an identical distance, interference will make their combined beam brighter than if the distances are different. So by reflecting one beam off of different layers of tissue, and moving the reference mirror until the combined reflected beam is brightest, the technique can measure the depths of each section of tissue and build up a detailed image of its structure. It has proved particularly useful in ophthalmology because the semi-transparent nature of retinal tissue makes it possible for OCT to penetrate to greater depths - up to several millimetres. When applied to the OND it can give information about both the shape and thickness of retinal nerve fibres, allowing even subtle changes to be tracked.

Such changes can be used to monitor the progression of diseases non-invasively and relatively cheaply. Unlike MRI, which is expensive and can require patients to remain still for an hour or more, OCT is increasingly available in clinics and can be carried out in a few minutes. "It's extremely inexpensive compared to other tests," says Valenti.

One possibility is to use OCT to monitor the effectiveness of treatments for neurodegenerative diseases, says Danesh-Meyer: "These drugs can have a lot of side effects, so if they are not having a benefit then you won't want to continue with them." _NS

The progress of brain tumours, multiple sclerosis, Alzheimer's, Parkinson's, and other brain diseases can be tracked over time using this non-invasive technique.

As the technology improves and allows for faster, less uncomfortable scans, it is likely that a routine baseline scan will be done on all adolescents as part of their permanent medical records. Should any new symptoms warrant it, later OCT scans can be compared with the baseline study to look for signs of brain pathology.

Longer lives mean more chances for new pathology. Pathology in the brain has been historically very hard and expensive to track over time. Newer technologies such as the OCT should allow medical scientists and practitioners to determine which persons need treatment, and which treatments provide the best result. The time saved by such new procedures should translate into a more functional lifespan.