Longevity Meme Newsletter, August 03 2009

August 03 2009

The Longevity Meme Newsletter is a weekly e-mail containing news, opinions, and happenings for people interested in healthy life extension: making use of diet, lifestyle choices, technology, and proven medical advances to live healthy, longer lives.



- A Research Fundraising Music Festival in Belgium
- A Likely Path for Progress in Applied Longevity Science
- A Regulatory Reminder
- Too Much Methionine is a Bad Thing
- Discussion
- Latest Healthy Life Extension Headlines


The Healthy Life Extension Society in Belgium is holding a music festival on September 12th in Ninove, near Brussels:


Funds raised will go to the SENS Foundation to help advance LysoSENS research. LysoSENS is a bioremediation program: efforts to find and develop bacterial enzymes that can break down the buildup of damaging metabolic byproducts that contribute to degenerative aging.



A little light fiction for you, illustrating what I see as a plausible path towards progress:


"Looking back from the perspective of 2035, I guess we should all be surprised that it took so long. The Vegas Group came together formally sometime in 2016, though the first kick-off meeting was the year prior at one of the bi-annual conventions for longevity research held in California. By that time, more than a dozen gene manipulations and other biotechnologies had been shown to significantly extend life in mice, but no progress was being made to develop these technologies for human use. The Vegas Group was a natural outgrowth of a decade of advocacy and anticipation for human enhancement technologies, coupled with the frustrating realization that no such technologies would be meaningfully developed, never mind made available to the public, under the regulatory regimes then in place in the US and Europe.

"There were initial fractures in the Vegas Group around the course of political change versus direct action - which led to the formation of another influential movement discussed elsewhere - but by 2017 the direct action contingent of the Vegas Group consisted of about a hundred people all told. Their declared objective was a distributed collaborative effort to (a) develop human versions of the most successful longevity and metabolic enhancements demonstrated in mice, and (b) cultivate hospitable medical groups in the Asia-Pacific countries. When these technologies were developed, the founding members would cast lots and carefully test upon themselves, in rotation, and though the agency of medical centers in Asia. In doing this the hope was to spur change in the public view and greater progress in the commercialization of these technologies - and of course to gain access to manipulations that were greatly extending life in mice. 'Pulling the big red lever,' as one of the founders said, a venture where altruism and greed collide to best effect."


People are used to and generally fairly accepting of whatever system they are used to, no matter how objectively terrible it is:


"It is only in the last couple of years that clinical trials have started for autologous stem cell therapies in the US. Or, to put it another way, for some time now unelected and largely unaccountable employees of the US government have forbidden US residents - on pain of criminal prosecution - from offering or making their own decisions about a medical technology commercially available elsewhere in the world. All the while, these bureaucrats impose vast costs on medical development concerns by insisting on largely pointless trials, continuing far past any reasonable trade-off between risk and reward, thereby greatly postponing the commercial introduction of these technologies in the US.

"Do you have responsibility for, or even the ability to make your own medical choices? Not according to people in positions of power at the FDA. Regulation in medicine has largely become an exercise undertaken for its own sake, as is the end result of any centralization of power. No-one's interests are being served save for those of the career bureaucrats in charge of forbidding new things. Everyone else gets to suffer due to the ball and chain shackled to medical progress, and due to being forbidden the basic, fundamental freedom to choose how to treat their own medical conditions."


Restricting the essential amino acid methionine without reducing overall calorie intake has been shown to capture many of the health and longevity benefits of calorie restriction in laboratory animals. Lowered dietary methionine levels change metabolic processes so that they cause less ongoing damage and degeneration. Supplementing methionine appears to have the reverse effect:


"Per recent research, it looks like too much methionine is a bad thing - biochemical measures of damage and good operation that are improved by lowering methionine intake are instead made worse when methionine is supplemented in the diet. This worsened set of metabolic processes occurs in addition to any further unpleasant effects produced by the visceral fat tissue most of us would gain in boosting our methionine intake the easy way - by eating more. ... today many Western human populations consume levels of dietary protein (and thus, methionine) 2-3.3 fold higher than the average adult requirement."


The highlights and headlines from the past week follow below.

Remember - if you like this newsletter, the chances are that your friends will find it useful too. Forward it on, or post a copy to your favorite online communities. Encourage the people you know to pitch in and make a difference to the future of health and longevity!




Cellular Reprogramming to Repair the Retina (July 31 2009)
From ScienceDaily: "researchers were able to program bone marrow stem cells to repair damaged retinas in mice [which] implies that blood stem cells taken from bone marrow can be programmed to restore a variety of cells and tissues, including ones involved in cardiovascular disorders such as atherosclerosis and coronary artery disease. ... To our knowledge, this is the first report using targeted gene manipulation to specifically program an adult stem cell to become a new cell type. Although we used genes, we also suggest you can do the same thing with drugs - but ultimately you would not give the drugs to the patient, you would give the drugs to their cells. Take the cells out, activate certain chemical pathways, and put the cells back into the patient. ... scientists describe how they used a virus carrying a gene that gently pushed cultured adult stem cells from mice toward a fate as retinal cells. Only after the stem cells were reintroduced into the mice did they completely transform into the desired type of vision cells, apparently taking environmental cues from the damaged retinas."

More on Mitochondrial Haplogroups and Longevity (July 31 2009)
Different haplogroups of human mitochondrial DNA appear to have some influence on longevity - though there are as many null or not terribly useful results as confirmations as the moment. This should not be surprising, given the importance of mitochondria in aging. Here's another study, this time in China: "To explore the effects of mtDNA haplogroups on the prevalence of extreme longevity (EL), a population based case-control study was conducted in Rugao - a prefecture city in Jiangsu, China. Case subjects include 463 individuals [older than] 95 yr (EL group). Control subjects include 926 individuals aged 60-69 years (elderly group) and 463 individuals aged 40-49 years (middle-aged group) randomly recruited from Rugao. We observed significant reduction of M9 haplogroups in longevity subjects (0.2%) when compared with both elderly subjects (2.2%) and middle-aged subjects (1.7%). Linear-by-linear association test revealed a significant decreasing trend of N9 frequency from middle-aged subjects (8.6%), elderly subjects (7.2%) and longevity subjects (4.8%). In subsequent analysis stratified by gender, linear-by-linear association test revealed a significant increasing trend of D4 frequency from middle-aged subjects (15.8%), elderly subjects (16.4%) and longevity subjects (21.7%) in females. Conversely, a significant decreasing trend of B4a frequency was observed from middle-aged subjects (4.2%), elderly subjects (3.8%) and longevity subjects (1.7%) in females." This all has the look of a field that will generate a big mountain of data before researchers establish any useful application of the science.

The Importance of Myelin (July 30 2009)
I've discussed the role of myelin in aging and neurodegeneration in the past, and here's more on the topic: "The effects of aging on myelinated nerve fibers of the central nervous system are complex. Many myelinated nerve fibers in white matter degenerate and are lost, leading to some disconnections between various parts of the central nervous system. Other myelinated nerve fibers are affected differently, because only their sheaths degenerate, leaving the axons intact. Such axons are remyelinated [by] the myelin-forming cells of the central nervous system, the oligodendrocytes [which] also continue to [build up] the myelin sheaths of intact nerve fibers ... It is presumed that the degeneration of myelin sheaths is due to the degeneration of the parent oligodendrocyte ... Whether there is a turnover of oligodendrocytes during life has not been studied in primates, but it has been established that over the life span of the monkey, there is a substantial increase in the numbers of oligodendrocytes. While the loss of some myelinated nerve fibers leads to some disconnections, the degeneration of other myelin sheaths and the subsequent remyelination [slows] down the rate conduction along nerve fibers. These changes affect the integrity and timing in neuronal circuits, and there is evidence that they contribute to cognitive decline."

HIF and Nematode Longevity (July 30 2009)
It's fascinating to see a system that evolution has apparently fine-tuned to minimize longevity - either increase its operation or disable it and longevity increases: "During normal development or during disease, animal cells experience hypoxic (low oxygen) conditions, and the hypoxia-inducible factor (HIF) transcription factors implement most of the critical changes in gene expression that enable animals to adapt to this stress. ... We examined the effects of HIF-1 over-expression and of hif-1 loss-of-function mutations on longevity in C. elegans ... We constructed transgenic lines that expressed varying levels of HIF-1 protein and discovered a positive correlation between HIF-1 expression levels and lifespan. The data further showed that HIF-1 acted in parallel to the SKN-1/NRF and DAF-16/FOXO transcription factors to promote longevity. HIF-1 over-expression also conferred increased resistance to heat and oxidative stress. We isolated and characterized additional hif-1 mutations, and we found that each of 3 loss-of-function mutations conferred increased longevity in normal lab culture conditions, but, unlike HIF-1 over-expression, a hif-1 deletion mutation did not extend the lifespan of daf-16 or skn-1 mutants. We conclude that HIF-1 over-expression and hif-1 loss-of-function mutations promote longevity by different pathways." The more longevity mutations that work in conjunction with one another the better.

Health, Common Sense, and Anticipation of Progress (July 29 2009)
Don't expect science to rescue you from the consequences of neglecting your health. It might, but frankly that doesn't seem to be a bet worth taking: "Amazing advances in anti-aging technologies may be just around the corner, but it's highly unlikely that any magic pill that undoes all the consequences of an unhealthy lifestyle will be among them. People who want longer, healthier lives for themselves and their children shouldn't abandon common sense while they wait for a scientific miracle. ... Already, two-thirds of Americans are overweight ... it seems as though many Americans are already acting as if medical cures to neutralize their bad habits are already available. Health-enhancing technology is advancing at rapid speeds. Aside from solid progress on caloric restriction, scientists are working on all sorts of projects that will no doubt extend life expectancy, such as growing new organs in the lab or fighting cancer with nano-drugs that target cancerous cells while leaving the healthy cells alone. The upside is that actual drugs based on these technologies seem closer to reality than ever before. The downside is that the possibilities these new technologies awaken sometimes entice people to throw away common sense, such as a healthy diet and at least a moderate exercise regimen."

Immune Therapies for Cancer Prevention (July 29 2009)
Here's a glimpse of the future of immune therapies for cancer. In years to come, researchers will have developed a vast library of biochemical signatures for precancerous tissue and very early cancerous growths. The immune system can be trained to attack those signs, thereby preventing known and catalogued forms of cancer from ever developing: "the new vaccine triggers the immune system to attack a faulty protein that's often abundant in colorectal cancer tissue and precancerous tissue. ... It works by spurring the body to manufacture antibodies against the abnormal version of a mucous protein called MUC1. While moderate amounts of the protein are found in the lining of normal intestines, high levels of a defective form of MUC1 are present in about half of advanced adenomas and the majority of colorectal cancers. The vaccine primes the immune system to monitor the gut for emerging cancers by teaching it to recognize abnormal MUC1. If an adenoma develops and begins to produce the faulty version of MUC1, the immune system will raise antibodies to attack and destroy the precancerous tissue. ... You would be using your immune system as a surveillance mechanism to prevent the development of malignancy."

Hair Regeneration Advances (July 28 2009)
Human nature being what it is, the application of cutting edge understanding of stem cells and cell signaling is as far advanced in the field of hair regrowth as in the field of heart regeneration. It's an ongoing demonstration of how we humans rank the relative values of being alive and looking good: "Histogen, Inc., a regenerative medicine company developing solutions based on the products of newborn fibroblasts grown under embryonic conditions, shared the results of the Company's preliminary clinical trial of Histogen's HSC human hair regrowth product for the first time ... HSC is a proprietary formulation of naturally secreted embryonic proteins, growth factors and contains the first naturally stabilized, bioactive solution of Wnt proteins and their cofactors, which have been implicated in the induction of new hair follicle formation and growth. ... 84.6% of the patients receiving one injection of Histogen's serum-free HSC showed an increase in terminal hair 12 weeks post-injection, with a statistically significant increase in the number of terminal hairs, cumulative hair thickness density and hair thickness mean." It's a press release, so assume some padding - but still, this is the sort of control over tissue behavior researchers are attempting in other fields.

Stem Cell Transplants and Degenerative Conditions (July 28 2009)
From ScienceDaily, an illustration of an issue in many degenerative conditions - transplanted stem cells are going to be just as affected by the underlying cause as are cells already in the body: "Accumulation of the synaptic protein alpha-synuclein, resulting in the formation of aggregates called Lewy bodies in the brain, is a hallmark of Parkinson's and other related neurodegenerative diseases. This pathology appears to spread throughout the brain as the disease progresses ... We demonstrated how alpha-synuclein is taken up by neighboring cells, including grafted neuronal precursor cells, a mechanism that may cause Lewy bodies to spread to different brain structures ... Our findings indicate that the stem cells used to replace lost or damaged cells in the brains of Parkinson's disease patients are also susceptible to degeneration ... Knowledge of the molecular basis of the intercellular transmission of alpha-synuclein may result in improved stem-cell based therapies with long-lasting benefits, by preventing the grafted cells to uptake alpha-synuclein or by making them more efficient in clearing the accumulated alpha-synuclein."

Convincing the Central Nervous System to Repair Itself (July 27 2009)
Researchers are working on the application of an interesting discovery: "Repair of the central nervous system and restoration of voluntary motor activity through axonal re-growth has long been considered impossible in mammals. [Researchers have] recently shown that an essential component interfering with regeneration was due to the activity of astrocytes, feeder cells that surround neurons. ... astrocytes synthesize two particular proteins (glial fibrillary acidic protein (GFAP) and vimentin), which isolate the damaged neuron to prevent interference with the operation of the central nervous system. While the protection is initially useful, in the long run it induces formation of impermeable cicatricial tissue around the neuron, thus constituting impenetrable scarring hostile to axonal regeneration and hence to propagation of nervous impulses. In the event of severe injury, the scarring engenders motor paralysis. ... the researchers pursued a strategy aimed at developing a therapeutic instrument to block formation of cicatricial tissue ... the researchers succeeded in controlling the reaction of astrocytes and when the latter were cultured with neurons, they promoted neuronal survival and triggered axonal growth."

Stem Cells in Every Implant and Medical Tool (July 27 2009)
Why not incorporate stem cells into every implant and medical tool that has prolonged contact with injured tissue? From ScienceDaily: "biomedical engineering students have demonstrated a practical way to embed a patient's own adult stem cells in the surgical thread that doctors use to repair serious orthopedic injuries such as ruptured tendons. The goal, the students said, is to enhance healing and reduce the likelihood of re-injury without changing the surgical procedure itself. ... , the students have begun testing the stem cell–bearing sutures in an animal model, paving the way for possible human trials within about five years. The students believe this technology has great promise for the treatment of debilitating tendon, ligament and muscle injuries, often sports-related, that affect thousands of young and middle-aged adults annually. .... Using sutures that carry stems cells to the injury site would not change the way surgeons repair the injury, but we believe the stem cells will significantly speed up and improve the healing process. And because the stem cells will come from the patient, there should be no rejection problems."



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