Longevity Meme Newsletter, August 11 2008

August 11 2008

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.



- Attitudes of Researchers to Engineered Longevity
- There are Few Old Fat People
- Hints of the Importance of Methionine
- Discussion
- Latest Healthy Life Extension Headlines


A recent paper suggests that the split of attitudes to healthy life extension in the aging research community is much the same as in the public at large - which is to say that a great many gerontologists don't consider engineering longevity to be desirable or a priority:


"Some saw a limit to the extension of human life, while others did not. Some felt that research into the fundamental ageing process was a priority; others did not. Researchers tended to weigh up the potential risks and benefits of life extension with most expressing a personal interest in life extension that was contingent on the technology providing a good quality of life. Some participants were not interested in the prospect of life extension for personal reasons, because they felt the potential risks outweighed the potential benefits, or because life extension raised issues of justice and equity."

It is hard to envisage a world in which cancer researchers talked the same way about the goals of their research. What good is understanding aging if it doesn't result in initiatives to eliminate the massive, world-wide suffering and death that aging causes?


There are old people and fat people, but there are few old fat people. As we count the years until the advent of working rejuvenation technologies, medicine capable of repairing the biochemical damage of aging, it is worth paying attention to the mundane issues that will cut your time and health short:


"Structural models have the ability to unravel the complicated simultaneous relationship between body weight, disability, and mortality along the aging process. Using longitudinal data from the Medicare Current Beneficiary Survey from 1992 to 2001, we constructed a structural model to estimate the longitudinal dynamic relationship between weight, chronic diseases, functional status, and mortality among the aging population.

"The elderly with normal weight at age 65 experience higher life expectancy and lower disability rates than the same age cohorts in other weight categories. The interesting prediction of our model is that the average body size of an elderly cohort will converge to the normal weight range through a process of survival, senescence, and behavioral adjustment."

Put on visceral fat and keep it over the years at your own risk. The data is pretty clear as to what the results will be: a shorter, less healthy life, and greater chance of missing out on the longevity science of the future:



Those of you following research into the biochemistry of calorie restriction might find this interesting. You'll recall that reduction in intake of the essential amino acid methionine seems to be an important driver of the health and longevity benefits provided by calorie restriction. Recent work suggests that alterations to methionine biochemistry might also be behind some other modern discoveries in engineered mammalian longevity:



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!




To view commentary on the latest news headlines complete with links and references, please visit the daily news section of the Longevity Meme: http://www.longevitymeme.org/news/

Some More Calorie Restriction Correlations (August 08 2008)
Some solid correlations in this paper, but I'm not sold on the suggested mechanism of action. Eating fewer calories definitely slows down the manifestations of aging, but researchers have a way to go yet to fully explain why this is so in each case: "iron accumulates with senescence in several organs, but little is known about iron accumulation in muscle and how it may affect muscle function. In addition, it is unclear if interventions which reduced age-related loss of muscle quality, such as calorie restriction, impact iron accumulation. We investigated non-heme iron concentration, oxidative stress, [and] key indices of sarcopenia (muscle mass and grip strength) in male [rats] fed ad libitum (AL) or a calorie restricted diet ... iron levels in the gastrocnemius muscle of AL rats increased progressively with age. Between 29 and 37 months of age, the non-heme iron concentration increased by approximately 200% in AL-fed rats. Most importantly, the levels of oxidized RNA in gastrocnemius muscle of AL rats were significantly increased as well. The striking age-associated increase in non-heme iron and oxidized RNA levels and decrease in sarcopenia indices were all attenuated in the calorie restriction (CR) rats. These findings strongly suggest that the age-related iron accumulation in muscle contributes to increased oxidative damage and sarcopenia, and that CR effectively attenuates these negative effects."

Aging, Inflammation, and Cancer (August 08 2008)
Less chronic inflammation, less cancer: "Cancer is generally recognized as an age-related disease. In fact, incidence and mortality rates of most human cancers increase consistently with age up to 90 years, but they plateau and decline thereafter. A low-grade systemic inflammation characterizes ageing and this pro-inflammatory status underlies biological mechanisms responsible for age-related inflammatory diseases. On the other hand, clinical and epidemiological studies show a strong association between chronic infection, inflammation and cancer and indicate that even in tumours not directly linked to pathogens, the microenvironment is characterized by the presence of a smouldering inflammation, fuelled primarily by stromal leukocytes. ... Centenarians are characterized by a higher frequency of genetic markers associated with better control of inflammation. The reduced capacity of centenarians to mount inflammatory responses appears to exert a protective effect towards the development of those age-related pathologies having a strong inflammatory pathogenetic component, including cancer. All in all, centenarians seem to carry a genetic background with a peculiar resistance to cancer which is also an anti-inflammatory profile."

An Interview With Ben Best (August 07 2008)
An interview with Cryonics Institute president and long-time healthy life extension advocate Ben Best can be found at Depressed Metabolism: "I believe that arrogance and complacency are poison for cryonics organizations, and competition is of value in shaking complacency (sometimes). I definitely think that it would be a bad idea for cryonics to have all the eggs in one organizational basket. ... There is already too much vulnerability to lawsuits and legal/political threats. More organizations in more locations (including more countries) would reduce this vulnerability. ... Eliminating or greatly reducing cryoprotectant toxicity would be the greatest possible step toward suspended animation through cryopreservation with vitrification. If suspended animation through cryopreservation became a reality there would be immediate acceptance and adoption by conventional medicine. Patient stabilization would be perfected by researchers all over the world and adopted in hospitals and other medical facilities. I think that too much research effort in cryonics is devoted to whole body vitrification, which is a side issue. Cryoprotectant toxicity needs to be [studied] with experiments directed toward understanding the molecular mechanisms on a theoretical level - not simply trial and error. Whole body vitrification could very well be achieved more quickly if cryoprotectant toxicity was the focus of study."

The Other Application of Stem Cell Science (August 07 2008)
EurekAlert! reminds us of the second main application for stem cell science: researchers "have produced a robust new collection of disease-specific stem cell lines, all of which were developed using the new induced pluripotent stem cell (iPS) technique. ... The cell lines the researchers produced carry the genes or genetic components for 10 different diseases, including Parkinson's Disease, Type I diabetes, Huntington's Disease, Down Syndrome, a form of combined immunodeficiency ('Bubble Boy's Disease'), Lesch-Nyhan syndrome, Gaucher's Disease, and two forms of Muscular Dystrophy, among others. ... the suite of iPS cell lines [marks] an important achievement and a very significant advance for patients suffering from degenerative diseases. These disease-specific iPS cells are invaluable tools that will allow researchers to watch the development diseases in petri dishes, outside of the patients. And we have good reason to believe that this will make it possible to find new treatments, and eventually drugs, to slow or even stop the course of a number of diseases." Advances that reduce the cost of research and increase efficiency will speed further progress. This is an excellent example of the type.

Another View of Gender Differences In Longevity (August 06 2008)
Via Time: "Another more complicated possibility [for women's longevity] is that women have two X chromosomes, while men have one. (Men have an X and a Y.) When cells go through aging and damage, they have a choice in terms of genes - either on one X chromosome or the other. Consider it this way: you have a population of cells, all aging together. In some cells, the genes on one X chromosome are active; in other cells, by chance, the same set of genes, with different variations, are active on the other X chromosome. Don't forget, we all have the same genes - the reason we differ is because we express different variations of those genes, like different colors of a car. Now, if one set of variations provides a survival advantage for the cells versus another, then the cells with the advantage will persist while the other ones will die off, leaving behind more cells with the genes on the more advantageous X chromosome. So, in women, cells can perhaps be protected by a slightly better variation of a gene on the second X chromosome. Men don't have this luxury and don't get this choice."

Transhumanism and Engineering Longevity (August 06 2008)
From the Hartford Advocate: "Transhumanism is the idea that it's OK to transcend the limitations of the body and brain ... Technologies, both large and small, could radically change the human experience. The mind reels with possibilities. Could we become cyborgs, with circuitry and metallic components seamlessly integrated into our bodies? Will there be nano-machines with artificial intelligence coursing through our bodies, fixing medical problems? Will we be able to dump our consciousness into computers or other machines? ... The possibilities are endless but, at least for now, human lives are not. ... Slowing body degeneration is a modest goal, and doesn't go far enough for some national anti-aging researchers. Aubrey de Grey, an energetic Englishman with a ZZ Top-length beard, is the chief researcher and evangelist for an anti-aging movement that views aging as a disease that can be cured, and cured soon. ... I think we have a 50 percent chance of getting there in around 25 years, so long as the early proof-of-concept work in mice is well-enough funded for the next 10 years or so."

Stem Cell Treatments in China (August 05 2008)
InformationWeek looks at one of the organizations that's putting stem cell research into clinical practice in China. The absence of stifling regulation means that this work proceeds much more rapidly, but rigorous data tends to come later in the process. The benefits of patient choice and researcher freedom should be obvious, however. "The company, Beike Biotechnology, uses nonembryonic stem cells to treat a variety of ailments including heart disease and neurological disorders such as cerebral palsy, spinal cord injury, muscular dystrophy, and optic nerve hypoplasia, a primary cause of blindness in children. Beike's technology, which hasn't been subjected to double-blind clinical trials of the sort required by the U.S. Food and Drug Administration, uses a combination of umbilical cord cells and stem cells derived from the patient being treated." The article notes that the company is working towards the near future use of induced pluripotent stem cells in therapy - a pace of development that is impossible in the present US regulatory system.

The Globe and Mail on Longevity Science (August 05 2008)
Mainstream articles on longevity science are slowly improving in quality - hopefully a sign of progress in advocacy for this research. From the Globe and Mail: "It's not pleasant to think about, but every cell type, every body part, has its own story of decline and decrepitude. Researchers [are] piecing together how we fall apart in the hope of finding ways to keep our bodies functioning well for longer. ... Figuring out a way to stop aging - or at least slow it down - is the modern version of Spanish explorer Ponce de Leon's quest for the fountain of youth. If researchers succeed, they could offer people the chance not only to live longer, but also to extend the healthy, active, even Olympian prime of their lives. ... Some researchers argue that aging is a simple matter of wear and tear. The average human lifespan has extended beyond 30 years only in the past couple of centuries. Different body parts are bound to break down in different ways now that we are regularly living past 80, half a century more than our hunter-gatherer ancestors. This damage is why age is a major risk factor in heart disease, cancer, diabetes and Alzheimer's. But others argue that aging is not the result of random breakdowns and failures but involves general processes common to many different cell types."

More Fuel For the DNA Damage Debate (August 04 2008)
Does the level of random damage to your nuclear DNA - genomic instability - have anything to do with general manifestations of aging? We know the correlation with cancer, but beyond that it's up for debate. This open access paper provides a new line of evidence: "Increasing genomic instability is associated with aging in eukaryotes, but the connection between genomic instability and natural variation in life span is unknown. We have quantified chronological life span and [genomic instability] in [yeast]. We show that genomic instability increases [during] chronological aging. The age-dependent increase of genomic instability generally lags behind the drop of viability and this delay accounts for ~50% of the observed natural variation of replicative life span in these yeast isolates. We conclude that the abilities of yeast strains to tolerate genomic instability co-vary with their replicative life spans. To the best of our knowledge, this is the first quantitative evidence that demonstrates a link between genomic instability and natural variation in life span."

Epigenetics in Aging (August 04 2008)
An interesting open access paper via PubMed Central: "Strictly speaking, 'epigenetics' refers to chromatin and DNA modifications that are heritable through cell division, but do not involve changes in the underlying DNA sequence ... Chromatin structure is not fixed. Instead, chromatin is dynamic and is subject to extensive developmental and age-associated remodeling. In some cases, this remodeling appears to counter the aging and age-associated diseases, such as cancer, and extend organismal lifespan. However, stochastic non-deterministic changes in chromatin structure might, over time, also contribute to the break down of nuclear, cell and tissue function, and consequently aging and age-associated diseases. ... it is apparent that chromatin structure does change with aging, in organisms as diverse as yeast and mammals. However, with the exception of Sir2 in yeast, the extent to which this impacts the aging process has not yet been defined. ... the effects of chromatin on aging are likely to be complex and bidirectional. To test and define the impact of specific epigenetic determinants on aging will be a challenging task."



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