Total Brain Network Imaging Reveals Efficiency Loss w/ Ageing

“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?

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

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

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

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

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

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?

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?

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

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

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

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

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

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

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

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

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

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

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?

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.