Longevity Meme Newsletter, November 20 2006

November 20 2006

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 Few More Resveratrol Links For the Road
- Targeting Antioxidants to Mitochondria
- Discussion
- Latest Healthy Life Extension Headlines


A cautionary note, a scientific paper generously offered in full, and thoughts on resveratrol from the respectable side of the blogosphere are wrapped up for your convenience in this Fight Aging! post:


"The interesting question to me is to what degree all of this manipulation of genetic expression and biochemistry via diet, drugs and other methodologies will be found to boil down to effects on a few core processes. To put it another way, how much of the benefit of calorie restriction stems from lacking fat, how much from low levels of inflammation, and so forth?

"I don't think we'll be left hanging for too many more years insofar as answers to these sorts of questions go. Metabolic manipulation may not be the most efficient path forward for healthy life extension, but it's most interesting to see answers, understanding and further questions in equal measure starting to flow thick and fast."


If your knowledge of antioxidants stops right around "they're good for you, right?" then I recommend you take a look at a couple of recent posts and articles. I'm going to be talking about mitochondria, free radicals and antioxidants, so read this guide to the territory first:


"Scientists generally concur that accumulated damage throughout the body due to free radicals is one important root cause of age-related degeneration - but the devil is in the details. The vast, overwhelming majority of those free radicals are generated by your own metabolism as an unavoidable byproduct. The rate of free radical generation increases greatly with age as the basic mechanisms of your of metabolism are themselves damaged by the free radicals they created. This is not a one-step process, however."

Antioxidants eat free radicals. The best antioxidants are very, very good at it, but not all uses of antioxidants are the same; as the mitochondrial free radical theory of aging suggests, you're not going to see significant benefits (such as, say, a 20% extension of life span in mice) unless antioxidants end up in your mitochondria, at the leverage point for this form of age-related damage:


That result of a fifth more healthy life in mice was obtained via gene therapy, and hence not something you're likely to see applied to humans any time soon. But a Russian group has apparently found a way of localizing ingested antioxidants to the mitochondria:


They are claiming much the same level of life extension in mice; as a drug, this is something you might just see work its way through the regulatory system within a decade, provided the science is verified and otherwise pans out.

The normal caveats apply - as for resveratrol, if that works out, this is only a way of slowing aging. It will be of little benefit to those already old and riddled with free-radical-producing cells populated by damaged mitochondria. Spending the hundreds of millions needed to develop a product that slows the rate at which the damage of aging accumulates is simply far less efficient than spending that money to develop repair technologies:


The resources exist to develop both lines of research in parallel, but those resources are not yet applied to the problem, and the lion's share of attention goes to slowing, not repairing. That is going to have to change if we want to live far longer, healthier lives:



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!


Founder, Longevity Meme



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/

Debates in Alzheimer's Science (November 19 2006)
Scientists are people like the rest of us, and people have issues with change - even those working to create that change. So all fields of science have a certain inherent degree of dogma versus heresy; on the one hand, funding organizations want the best chance of placing resources where they will do the most good, and so support the consensus view. On the other hand, leaps in understanding come from challenges to the orthodoxy. A healthy field is rife and energetic with heresy - where many new and different ideas are tested by the scientific method. This Post-Gazette pieces gives a taste of how this all looks in Alzheimer's research: "For more than 20 years, the leading theory has held that sticky blobs in the brain called amyloid plaques cause Alzheimer's. Because that idea has numerous problems, doubters argued that the plaques might be innocent bystanders to the real, 'upstream' culprit. If so, targeting the plaques, or the rogue protein called beta-amyloid that forms them, would do nothing to help [those] who suffer from Alzheimer's."

A Reminder: Obesity and Inflammation (November 19 2006)
Medical News Today reminds us of the link between excess fat, inflammation, and earlier onset of age-related disease: "a high fat diet draws inflammatory cells into fat tissue, which prevents the tissue from storing the fats we eat. When the tissue can not store these fats, they end up in the liver and muscle, which in turn causes diabetes and heart disease. ... [fat cells] produce molecules called chemokines, which attract inflammatory white blood cells into fat tissue. Both macrophages and T cells, which play a critical role in the immune system, accumulate in fat tissue, beginning the process that leads to disease." While researchers are talking about a drug-based solution to squash inflammation from fat, there's a better way: lose the fat. Even better, choose a healthy lifestyle that prevents you from collecting it in the first place.

The Aging Sense of Smell (November 18 2006)
Everything declines as we age; there is so much to be investigated that bypassing our ignorance by embracing a strategy based on repairing known classes of age-related cellular damage - rather than tracking down every last consequence, one by one - is a very attractive option. From Medical News Today: "Aging has a profound effect on olfactory function and olfactory sensitivity ... we may also uncover changes that are common to many parts of the brain and that form a basis for age-related changes in the brain and its functions. ... In both Alzheimer's and Parkinson's diseases, early onset of changes and pathology in the sense of smell suggest a central involvement of olfactory systems in aging and age-related diseases. ... Yet, little has been done in the development of animal models for studying the cellular and molecular changes in the olfactory system as a result of aging."

What Can We Learn From Germ Line Cells? (November 18 2006)
Ouroboros looks at that little piece of immortality that resides in all of us: "The germ line (the cell lineage from which reproductive cells are derived) is replicatively immortal - distinct from the soma, where most cells capable of division have a strictly limited replicative capacity, if they're not entirely postmitotic. Why? ... Understanding the proliferative perseverance of the germ line is particularly important when one considers the way in which germ cells violate one of the time-honored justifications for a replicatively limited soma, namely, that an unlimited replicative capacity would place a cell at risk for initiating cancer ... Certainly, germ-line derived tumors are not unheard of, but they are rare, even though everyone's got germ cells - so these lineages serve as an example of replicative immortality that does not confer an unusual risk of carcinogenesis." Does the key to engineering cancer-free human biochemistry lie somewhere in our germ cells? We will probably know - in detail - the answer to that question within the next twenty years.

More Spurring Cells To Action (November 17 2006)
The BBC reports on another way to potentially guide cells in your body to take that extra step to repair damage: "cells in the heart's outer layer can migrate deeper into a failing organ to carry out essential repairs. The migration of progenitor cells is controlled by a protein called thymosin beta 4, already known to help reduce muscle cell loss after a heart attack. ... Progenitor cells are similar to stem cells, in that they have the potential to turn into different types of adult tissue. However, it had been thought there was no ready source of these cells in the heart, and to carry out repairs they had to be summoned up from the bone marrow. The latest research is the first to show that they actually reside within the heart tissue itself. ... when treated with thymosin beta 4, these adult cells have as much potential as embryonic cells to create healthy heart tissue ... In the future if we can figure out how to direct the progenitor cells using thymosin beta 4, there could be potential for therapy based on the patients' own heart cells."

Wnt and Innate Regeneration (November 17 2006)
EurekAlert! notes that researchers have "been able to regenerate a wing in a chick embryo - a species not known to be able to regrow limbs - suggesting that the potential for such regeneration exists innately in all vertebrates, including humans. ... vertebrate regeneration is under the control of the powerful Wnt signaling system: Activating it overcomes the mysterious barrier to regeneration in animals like chicks that can't normally replace missing limbs while inactivating it in animals known to be able to regenerate their limbs (frogs, zebrafish, and salamanders) shuts down their ability to replace missing legs and tails. ... In this simple experiment, we removed part of the chick embryo's wing, activated Wnt signaling, and got the whole limb back - a beautiful and perfect wing. By changing the expression of a few genes, you can change the ability of a vertebrate to regenerate their limbs, rebuilding blood vessels, bone, muscles, and skin - everything that is needed."

More on Resveratrol, Sirtuins (November 16 2006)
From the New York Times, another angle on the calorie restriction mimetic resveratrol and sirtuin research: "very large doses of resveratrol protected mice from gaining weight and from developing metabolic syndrome. Dr. Auwerx attributes this change in large part to the significantly increased number of mitochondria ... the treated mice were able to burn off more fat and thus avoid weight gain and decreased sensitivity to insulin ... The principal theory [is] that the sirtuins somehow sense the level of energy expenditure in living cells and switch the body's resources from reproduction to tissue maintenance when food is low. ... The [switch] involves specific action to stave off the major degenerative diseases of aging, such as cancer, diabetes, heart disease and neurodegeneration. ... One serious uncertainty is whether, in the mouse experiments, resveratrol in fact acted through the sirtuins or by some other unknown mechanism." It won't be too long now before we find out what's really going on under the hood in calorie restriction.

From the Wellcome Trust (November 16 2006)
As noted at Ouroboros, the latest issue of Wellcome Focus is evidence for the wider spread of positive thinking on scientific intervention in the human aging process. "As one can immediately grasp from the title page, the tone of the coverage is very favorable to anti-aging therapy and lifespan extension as a concept. There are multiple articles about the sociology, biology, and biomedicine of aging - all woven together with a hope-filled depiction of what might be possible in the near term. ... The hope that we may be able to intervene successfully to secure better health in old age draws strength from the realisation that ageing is not programmed, but results instead from the gradual, lifelong accumulation of faults. Although the build-up of damage will not be easy to tackle, we can now see that the underlying biology of ageing is likely to be more malleable than was previously thought, when ageing was viewed somewhat fatalistically as part of an immutable programme."

Spurring Stem Cells to Action (November 15 2006)
A potential alternative to first generation (often autologous) stem cell therapies based on extraction and transplantation would be to guide stem cells already present in the body into actions they would not otherwise have taken. From Yahoo! News: researchers "injected a natural protein from the body - leukemia inhibitory factor, or LIF - into a part of the brain of adult mice where stem cells reside. This fostered the production of up to six times the usual count of adult neural stem cells. ... While this study involved mice, the researchers noted that human adults also harbor neural stem cells in their brains. The brains of neurodegenerative disease patients appear to try to marshal their own neural stem cells to replace dying cells, but not in the numbers sufficient to do the job. ... The adult brain does try to repair itself by stimulating its own neural stem cells. But obviously it's not enough. So what we're trying to do here is kick it in the pants and increase the number of neural stem cells."

More Impressive Cancer Research (November 15 2006)
PhysOrg.com notes continuing improvement in prospective cancer therapies based on dendrimers: "After a single intravenous injection, every mouse treated with the dendrimer-drug construct survived until the end of the 60-day experiment and every mouse showed complete tumor regression. In contrast, none of the mice treated with only doxorubicin survived, which an average survival time of only 24 days." A single shot cure for cancer, in other words - nice work. Enthusiasm is in view out there in the nanotechnology community: "There's that word: cures! If nanotechnology, at this early stage, can make a difference for cancer, this should greatly increase public support for nanotech R&D, especially nanomedicine. Then we can go after heart disease, Alzheimer's, AIDS, and ... aging itself. It's all about how the molecules are arranged."

Learn From the Misfortunes of Others (November 14 2006)
If you must learn from harsh experience, make sure it's the harsh experience of others. Insofar as your health goes, you only get one shot at living a long and healthy life as best you can. Why cut yourself short in ways that are shown to reduce lifespan? From JAMA: "High grip strength and avoidance of overweight, hyperglycemia, hypertension, smoking, and excessive alcohol consumption were associated with both overall and exceptional survival. In addition, high education and avoidance of hypertriglyceridemia were associated with exceptional survival, and lack of a marital partner was associated with mortality before age 85 years. ... probability of survival to oldest age is as high as 69% with no risk factors and as low as 22% with 6 or more risk factors. The probability of exceptional survival to age 85 years was 55% with no risk factors but decreased to 9% with 6 or more risk factors. ... avoidance of certain risk factors in midlife is associated with the probability of a long and healthy life among men."

Accelerated Aging and Arthritis (November 14 2006)
From ScienceDaily: "The observation that people with rheumatoid arthritis (RA) die at a younger age than people without this disease is not new, but arthritis experts don't fully understand the causes of the increased mortality rates. ... RA and other diseases can cause multiple systems within the body to age more rapidly than expected. Cells affected by diseases begin to show signs of what's called accelerated aging - damage at the molecular level resulting in poorer function. ... As expected, the observed survival rate for people with RA was consistently less than the expected survival rates for people in the general population. Researchers estimated that the RA patients in the study group aged at approximately 1.25 times the rate of people in the general population. Another way to express this finding is that during each 10-year time span, people with RA, in effect, age 12.5." An obvious place to look would be the long-term effects of chronic inflammation on the body.

Regenerative Medicine, Cardiology (November 13 2006)
Drug Discovery & Development takes a look at progress and practicalities in the first generation of stem cell therapies: "But exactly how does it all work? That's a critical question about cardiac regeneration using stem cells, and one that scientists don't yet have the answer to. They have theories, some more popular than others. ... In randomized trials in Europe, 70% to 80% of people got better. ... Are all patients who get stem cells going to get better? No. Just like with any other therapy, you have to select your patients correctly, and we're continually refining which patients may benefit. ... Right now, it's a little bit of the Wild Wild West out there, and there's a lot of hucksterism. It's hard to know what to believe and what not to. But I'm very bullish on this. I think the field of regenerative therapy will change the practice of cardiology as we know it." Early days yet.

Twenty Years Left For Cancer (November 13 2006)
Ever more scientists are willing to put forward estimated timelines for the end of cancer as a fatal age-related condition. Here's another, via the Australian: "Death from cancer - and possibly heart disease - will be a thing of the past within 20 years because of advances in genetic technology, an expert said today. John Shine, director of the Garvan Institute for Medical Research in Sydney, today said he believed while people would still get cancer in 20 years time, they would not die from it. Scientists now knew it was possible to develop 'smart' drugs which targeted particular disease-causing or susceptible genes and it was only a matter of time before there were drugs which could target cancer ... I think there's no doubt death from cancer will be confined to the annals of history, and I think a very similar thing will apply to heart disease."



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