Longevity Meme Newsletter, June 01 2009

June 01 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.



- Rationale For the My Bridge 4 Life Initiative
- How to Read the Output of the Scientific Method
- Lazy Immortality
- Discussion
- Latest Healthy Life Extension Headlines


As a part of recent reorganization, the Methuselah Foundation introduced its first short-term initiative: My Bridge 4 Life. Dave Gobel, the Foundation CEO, recently explained the rationale behind the initiative:


"The reason for MB4L is that we are working to reduce the 'aha! gap' or conceptual hurdle for the billions of folks for whom a leap straight to the idea of extending healthy life is too vast and daunting a gap.

"The new effort - focused on the short term and exemplified by MB4L - is designed to gain the positive attention of the 99.9% of the population who have been too busy to pay attention to the real underlying problems [of degenerative aging], but to whom life has handed a very sad but compelling imperative - i.e. "I (or my loved one) has Cancer (or some other life-threatening condition)!" The goal of MB4L is to provide serious, valid and relevant medical information, family and community support, education and hopefully lifesaving insights to such people at very low cost. At the same time while adding supporters and generating donations in behalf of the foundation and its longer-term mission.

"During their involvement with MB4L it will become clear to MB4L's participants that the real enemy to defeat is the insidious underlying process that made them or their loved ones vulnerable to the disease that eventually attacked them. In a sense, MB4L is a real bridge that saves lives both in the present AND in the future. It is a bridge that brings people to understand the larger goals at a time when they are willing and able to listen."


The scientific method is the greatest of inventions: it allows us to sift truth and progress from the natural human state of flawed work produced by flawed people. But it doesn't produce nice neat pronouncements come down from the mountain, and reading the output of the scientific community is a skill - just like reading financial market data or high literature in a foreign language. If you'd like a place to start, read the following Fight Aging! post:


The only cure for being unable to interpret results produced by the scientific community is to dive in and practice; understanding research is no different from any other skill. If you found the post above helpful, then you might try jumping in at the deep end with recent news on AGEs and Alzheimer's disease:


Advanced glycation endproducts (AGEs) are damaging biochemicals, side-products of metabolism that build up with age. They are notably linked with metabolic diseases like diabetes, chronic inflammation, and a range of other unpleasant things that go wrong with your biochemistry as you grow older. But nothing is as clear-cut as we'd like, and Alzheimer's research is an excellent example of a field in which you have to keep the big picture of varied connections and their plausibility in mind.


Scientists can do as good a job as theologians in pontificating on immortality when they are so inclined. Discussions arise from such areas as the Many Worlds Interpretation of quantum mechanics, pattern identity theories, and so forth:


"Wouldn't it be nice to wake up and find that we were all immortal? That would save a whole lot of work, uncertainty, and existential angst - and we humans are nothing if not motivated to do less work. The best of us toil endlessly in search of saving a few minutes here and a few minutes there. So it happens that there exist a range of metaphysical lines of thought - outside the bounds of theology - that suggest we humans are immortal. We should cast a suspicious eye upon any line of philosophy that would be extraordinarily convenient if true, human nature being what it is.

"Varied non-theological metaphysical speculations on immortality largely revolve around these points: (a) the existence of an extremely large universe in which replicas of you exist, and (b) that the continuation of a replica after your own sad demise is a satisfactory form of immortality. Needless to say, I'm cutting short at the neck a number of subtleties in that two line summary, but it's about the size of it. If you buy in to, say, the Many Worlds Interpretation of quantum mechanics (which a great many people in the field do) and you are fine with identifying your self as a specific pattern, no matter if there are discontinuities in the existence of that pattern, then you might argue that you are immortal."

The risk of buying into this sort of argument is that you relinquish efforts at extending healthy life in the here and now - and therefore suffer more from age-related conditions and die younger than you would have done. Not to mention failing to do an immense amount of good by helping many other people also live longer in good health. So I think you have to live as though what you see is what you get: an imperfect world, and one good shot at engineering new medical science to greatly extend healthy longevity. The risk of lazily doing otherwise is just too great.


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!




Forbes on Medical Tourism (May 29 2009)
The FDA forbids the development of new medical technologies long past the point at which any sane person would consider them a good risk, and in the process makes these technologies vastly more expensive. Medical tourism is a sane response to heavy-handed and unaccountable government employees: "Gregg Victor is one of the 1.5 million Americans who traveled abroad to get medical treatments last year. ... More than a few were pursuing new stem-cell-based treatments unavailable in the States ... 'I am not waiting for the FDA to rule to get treatments,' says Gregg Victor, who chose her clinic in Germany after spending a year and a half looking into stem cell treatments available all over the world. ... Jordan happened upon TheraVitae, a Bangkok-headquartered biotechnology company that markets 'VesCell stem cell treatments' via licensing agreements with four clinics in Thailand ... Thai doctors injected 25 million of his own stem cells into Jordan's heart. Twenty thousand miles, 22 days, a cardiac arrest and $43,000 later, he came home to his wife with an ejection fraction between 30% and 35%. Even Jordan's doctor had to admit he was happy with the results." Results are mixed, much as you'd expect. Caveat emptor, and do your research - but a great many people are materially benefiting from technologies still forbidden by their own governments.

Another Look at Hormesis (May 29 2009)
A little damage can be a good thing in a self-repairing system: "Oxidative stress has been linked to aging, cancer and other diseases in humans. Paradoxically, researchers have suggested that small exposure to oxidative conditions may actually offer protection from acute doses ... One major contributor to oxidative stress is hydrogen peroxide, converted from a type of free radical that leaks from the mitochondria as it produces energy. ... [Researchers] used the rich functional genomics toolbox of yeast to identify pathways involved in the cell's adaption to hydrogen peroxide. Adaption (or hormesis) is an effect where a toxic substance acts like a stimulant in small doses, but is an inhibitor in large doses. ... This finding may explain recent studies suggesting that eating less may, in fact, raise [oxidant] levels - and, in doing so, provide protection from acute doses of oxidants. This is counter to the hypothesis that caloric restriction extends lifespan in some species because it reduces [oxidants] produced as a by-product of the energy generated by mitochondria. ... It may be that adaption to oxidative stress is the main factor responsible for the lifespan-expanding effects of caloric restriction." Possibly, but my money is still on enhanced autophagy as the major mechanism.

Looking Back at the Free Radical Theory of Aging (May 28 2009)
From Ouroboros: "The free radical theory of aging (FRTA) was first advanced by Denham Harman more than 50 years ago. The theory proceeds logically from a small number of straightforward assumptions, based on observations from radiation biology ... Over a half-century, the FRTA has evolved substantially (eventually focusing on the mitochondria as a major source of the initially postulated endogenous radicals), and has lately been the subject of several reviews evaluating its explanatory power and extent of current acceptance. ... The basic chemical process underlying aging was first advanced [in] 1954: the reaction of active free radicals, normally produced in the organisms, with cellular constituents initiates the changes associated with aging. The involvement of free radicals in aging is related to their key role in the origin and evolution of life. The initial low acceptance of the FRTA by the scientific community, its slow growth, manifested by meetings and occasional papers based on the theory, prompted this account of the intermittent growth of acceptance of the theory over the past nearly 55 years."

Complicating Alzheimer's Disease (May 28 2009)
From MedPage Today: "The pathological features of Alzheimer's disease -- tangles, neuritic plaques, and diffuse plaques -- may not be as representative of clinical dementia in the very old as in the younger elderly ... For example, a 75-year-old with a moderate-to-severe burden of neurofibrillary tangles in the hippocampus was much more likely to have had a dementia diagnosis than a 95-year-old with the same amount of tangles. ... it will become even more important to understand the atypical cases of older old persons who are cognitively intact despite having neurodegenerative-disease lesions. ... their findings suggest that current disease-based classifications made on the basis of discrete entities, such as Alzheimer's disease, vascular dementia, or mixed dementia, are [a] simplification." One thing that leaps to mind here is that a 95-year-old is much less likely than a 75-year-old to have been overweight and suffered metabolic syndrome (by virtue of having avoided death by all the age-related conditions that follow that state) - and Alzheimer's appears to be very much like diabetes in terms of its relationship to metabolism and excess fat.

Telomere Length and Years of Healthy Life (May 27 2009)
Shorter telomeres appear to be a bad thing, but their relationship to longevity is not straightforward: "Although telomere length (TL) is known to play a critical role in cellular senescence, the relationship of TL to aging and longevity in humans is not well understood. In a large biracial population-based cohort, we tested the hypotheses that elderly persons with shorter TL in peripheral white blood cells have poorer survival, shorter life span, and fewer years of healthy life (YHL). ... TL [was] not associated with overall survival or death from any specific underlying cause including infectious diseases, cancer, or cardiac and cerebrovascular diseases. TL, however, was positively associated with more YHL. Findings suggest that TL may not be a strong biomarker of survival in older individuals, but it may be an informative biomarker of healthy aging." Which suggests to me that telomere length is broadly associated with all sorts of poor health and age-related decline, but modern medicine is blunting the resulting hit to life expectancy. Questions of cause and effect remain, however: is telomere shortening merely a reflection of other age-related damage, or a fundamental damage-causing process itself?

Working With Neurogenesis (May 27 2009)
What could medical science do with a reliable way of generating new neurons in the brain? "Researchers have identified a new mechanism that plays a central role in adult brain stem cell development and prompts brain stem cells to differentiate into neurons. Their discovery, known as Integrative FGFR1 Signaling (INFS) [is] considered capable of repopulating degenerated brain areas, raising possibilities for new treatments for Parkinson's disease, Alzheimer's disease and other neurodegenerative disorders ... The approach uses gene engineering and nanoparticles for gene delivery to activate the INFS mechanism directly and promote neuronal development. The INFS-targeting gene can prompt these stem cells to differentiate into neurons. ... the research team set out to see if it is possible to generate a wave of new neurons from stem cells and direct them to the affected areas. ... [There is] the need for further development of gene delivery methods for the treatment of neuronal loss. ... Targeting the INFS mechanisms by small molecules could potentially replace the need for gene transfers and create a classical drug therapy for the neuronal loss."

Rapamycin, Autophagy, and Longevity (May 26 2009)
An exercise in joining the dots here: TOR, or target of rapamycin, is known to be important in calorie restriction in species ranging from yeast to mammals. We also know that autophagy, the process by which cells recycle damaged components and break down unwanted molecules, appears to be required to gain the benefits of calorie restriction. This paper links autophagy, life span, and rapamycin in yeast, closing the circle: "Rapamycin is an antibiotic that stimulates autophagy in a wide variety of eukaryotes, including the budding yeast Saccharomyces cerevisiae. Low concentrations of rapamycin extend yeast chronological life span (CLS). We have recently shown that autophagy is required for chronological longevity in yeast, which is attributable in part to a role for autophagy in amino acid homeostasis. We report herein that low concentrations of rapamycin stimulate macroautophagy during chronological aging and extend CLS." Many lines of evidence point towards autophagy as an important determinant of longevity. I suspect this is because more autophagy means fewer damaged mitochondria, but that thesis is as yet unsupported by a good weight of evidence.

More Anti-Cancer Viral Engineering (May 26 2009)
From ScienceDaily: scientists "have tamed a virus so that it attacks and destroys cancer cells but does not harm healthy cells. They determined how to produce replication-competent viruses with key toxicities removed ... Cellular microRNA molecules regulate the stability of [messenger RNA] in different cell types, and this newly-understood mechanism provides the possibility to engineer viruses for cell-specific inactivation. [This is] a mechanism whereby wild type virus potency could be maintained in tumor cells but the virus could be 'turned off' in tissues vulnerable to pathology. ... This approach is surprisingly effective and quite versatile. It could find a range of applications in controlling the activity of therapeutic viruses, both for cancer research and also to engineer a new generation of conditionally-replicating vaccines. ... Although the current tumor-killing virus is useful in mice, transfer of the technology into the clinical setting will require re-engineering of the virus to overcome virus pathologies seen in humans, and it will be at least two years before this can be tested in the clinics."

Update on Catalase in the Mitochondria (May 25 2009)
You might recall that mice genetically engineered to generate more of the antioxidant catalase in their mitochondria live longer in good health. Similarly, ingested antioxidant compounds engineered to migrate to the mitochondria have much the same effect (but don't go looking for that in the stores - it's only in the lab so far). Other ingested antioxidants are a wash - no effects, or negative effects. Here's an update from the group working on catalase-producing mice: "Age is a major risk for cardiovascular diseases. Although mitochondrial reactive oxygen species have been proposed as one of the causes of aging, their role in cardiac aging remains unclear. We have previously shown that overexpression of catalase targeted to mitochondria (mCAT) prolongs murine median lifespan by 17% to 21% ... Cardiac aging in mice is accompanied by [a number of characteristic biochemical and structural forms of damage and change in the heart, heart tissue, and heart cells]. All of these age-related changes were significantly attenuated in mCAT mice." Much as one would expect: less damage to cells and tissues means a longer life, on average.

No Alzheimer's in Other Primates (May 25 2009)
Researchers have uncovered a difference that may explain why other primates don't suffer from Alzheimer's disease; it remains to be seen what can be done with this information. Via Yahoo! News: "Humans get the devastating neurological disorder known as Alzheimer's disease, but their closest evolutionary cousins don't. Even more inexplicable is the fact that chimpanzee and other non-human primate brains do get clogged with the same protein plaques that are believed by many to cause the disease in humans. ... a 'tag' molecule used to track plaque build-up latches easily onto plaques in human brains but not in those of apes and monkeys, suggesting that there is a basic structural difference between the two types of plaque. Figuring out the difference, they said, could lead to ways to render human amyloid plaques as harmless in human brains as they are in the brains of other primates. ... This is another finding of unknown significance, but it is a finding. None of us know why these higher primates don't get Alzheimer's disease, but we don't [fully understand the mechanisms that lead to human] Alzheimer's disease either. Where it leads us, I don't know."



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