Not Over the Hill Yet, Baby!

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

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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:

1. Alzheimer's and other neurodegenerative disease
2. Stroke
   
3. Diabetic Neuropathy
4. Hemorrhagic Shock
5. Sexual Dysfunction for males and females
   
6. Obesity
7. Anorexia and Cachexia
8. Depression
9. Anxiety
10. 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

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

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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

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.

SIRT 6 May Have Important Aging Role

SIRT1 has been the most studied of the SIRT family of proteins, but mice studies suggest that SIRT6 may also plan an important role in aging:

A formerly underappreciated member of the sirtuin family of proteins may hold the key to youthfulness and is the first sirtuin shown to specifically govern the activity of genes, scientists report.

Researchers from Stanford University report in the Jan. 9 Cell that SIRT6, a sibling of the aging-related protein SIRT1, is an important regulator of gene activity in mice.

“This is a big, big discovery,” says Raul Mostoslavsky, a chromatin biologist at the Massachusetts General Hospital Cancer Center and Harvard University Medical School in Boston. And one, he adds, that could shift some of the limelight away from SIRT1, a molecule implicated in the aging process.

“I’d say 95 percent of the literature is on SIRT1. I think that is going to change,” Mostoslavsky says. “People will start realizing that other sirtuins are probably important for regulating many biological functions.”

Mostoslavsky was not involved with the current study, led by Katrin Chua and Howard Chang of Stanford University, but he is familiar with all seven of the sirtuins found in mammals. He was the first to genetically engineer mice to lack each individual member of the sirtuin family. Mice missing SIRT6 develop normally for the first weeks of life, but then rapidly decline as if they are prematurely aging. The mice die by one month of age, ultimately of low blood sugar.

Last year, Chua’s group showed that SIRT6 is an enzyme that specifically removes a chemical called an acetyl group from a specific spot on a histone protein. Histones wrap DNA into a package that can fit inside the cell and are also important for controlling which genes turn on and off. Removing acetyl groups from histones generally shuts genes off.

Chua’s group has also previously shown that SIRT6 helps keep genomes stable and protects the ends of chromosomes, known as telomeres, from damage.

Now Chua’s and Chang’s groups together show that SIRT6 works with a master regulatory complex called NFkappa-B to govern activity of genes associated with aging, inflammation, immunity and metabolism. When SIRT6 is missing, NFkappa-B becomes hyperactive and turns up activity of aging-linked genes.

Reducing the amount of NFkappa-B in SIRT6-deficient mice restores normal life span and corrects many of the premature aging symptoms. But the mice still have low blood sugar, and many other genes not regulated by NFkappa-B show abnormal activity when SIRT6 is absent. _ScienceNews

Whether these findings are applicable to normal aging in mice or humans remains to be proven. Nevertheless, continued explication of the mechanisms of gene expression across the normal lifespan of mammals will eventually provide avenues to modifying the aging process.

Brain - Cooling Techniques

Scientists and physicians are developing new brain - cooling techniques to reduce morbidity after heart attacks (and presumably strokes) and to aid successful resuscitation after heart attacks. One device, like a reverse hair drying hood, cools the scalp and its blood vessels, achieving about 1 degree C cooling of the brain per hour. Another device sprays a refrigerant deep into the nose to indirectly cool arteries passing nearby, heading for the brain. The nasal device cools the brain by 2.4 degrees C per hour. A third device uses an icy slurry lavage into lung airways, to cool blood passing into the carotid arteries to the brain.

For some time, doctors have observed that cooling patients following a heart attack can reduce brain damage. Although they are not yet sure of the mechanism behind this effect, researchers suspect that cooling the brain by 4 °C, to around 33 °C, reduces the metabolism of brain cells, reducing their hunger for oxygen for the crucial moments during which blood is in short supply. Damage seems to be reduced even if the brain is only cooled once the heart has been restarted, suggesting that cooling may also slow the release of toxic chemicals from neurons and glial cells - a process called the ischaemic cascade, which triggers further brain-cell death up to 24 hours after a cardiac arrest or stroke.

Previously, doctors have induced "therapeutic hypothermia" by applying ice packs or cooling blankets to the whole body, or injecting cold saline solution into the veins. However, cooling the whole body can increase the risk of infection and pneumonia, so researchers are now building targeted devices that chill the brain directly.

...The ice slurry can cool the brain by 4 °C - the safe limit before damage is risked - in less than 15 minutes, says Kasza, who has so far tested the technique on pigs. His team is investigating whether their icy slurry could also be applied to the kidneys (see picture) and the heart during invasive surgery, to prevent damage to the organs when blood flow is suspended for the operation.

One of the main advantages of all the new techniques is that they are simple enough to apply before or immediately after resuscitation following a heart attack - minimising the delay between the heart malfunction and cooling the brain. "A paramedic could deliver the slurry," says Kasza.

What's more, a recent study in pigs suggests that immediate cooling with the RhinoChill device, besides reducing brain damage, could also improve the chances of success of the resuscitation itself, although it is not yet certain why this is. Sixteen pigs were given a heart attack, and then left for 15 minutes before CPR was applied to start their hearts again. Of the eight pigs cooled using the RhinoChill system during CPR, six survived, compared with just two of the eight who were left unchilled (Resuscitation, DOI: 10.1016/j.resuscitation.2008.03.087).

Rapid application of such techniques could be particularly good news for stroke victims. "Clot-busting drugs can only be administered after diagnosis and brain scans in the hospital," says Andrews. "But applying therapeutic cooling at the scene of the stroke could lengthen the time window in which the drugs are effective - before too much damage has occurred," he says. _NewScientist

These techniques are a far cry from the advanced cryonics and vitrification methods needed for long - term organismic storage or hibernation. But experiments with them, and experience using them should add to the knowledge needed to develop the longer - term methods.