Fight Aging!

LONGEVITY MEME NEWSLETTER
January 14 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.

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CONTENTS

- Why Should You Care About Biogerontology?
- Bulk Biochemical Changes With Aging
- Discussion
- Latest Healthy Life Extension Headlines

WHY SHOULD YOU CARE ABOUT BIOGERONTOLOGY?

Researcher Chris Patil demonstrates that explaining aging research to laymen is not so different from advocating aging research to the public at large:

https://www.fightaging.org/archives/001388.php

"Surprisingly, comprehensive cures for all heart disease, stroke, diabetes and cancer are predicted to have rather modest effects on [average lifespan]. Such cures, in any event, are still far away even after years of study. Aging is the primary risk factor for these (and many other) diseases; as a relatively new science, biogerontology holds greater promise for near-term radical improvements in healthspan. The Olshansky projections really blew them away, especially when coupled with a few words about the longevity increases we've achieved with single-gene changes and dietary restriction in model organisms. Then I showed a pie chart comparing the NIH funds spent on diseases to those spent on basic aging research. Gasps."

Next to nothing goes toward aging research, as there are strong financial and social disincentives for researchers to become involved in the first place. Regulatory bodies in the US do not recognize aging as a medical condition, and therefore will not approve therapies aimed at extending longevity by directly attacking the processes of aging. This closes off the path to finance through commercialization and venture investment - that has a very strong effect on career choice and academic investment in a field:

https://www.fightaging.org/archives/2007/07/another-view-of-the-problem/
https://www.fightaging.org/archives/2007/07/the-problem-illustrated/

"Why, despite the great range of potential applicable biotechnology, do we not see hundreds of millions of dollars invested in startups attempting to address the aging process? The answer is buried in this New York Times article on Sirtris: Dr. Westphal and Mr. Sinclair stress that they are not working to 'cure' aging, a condition that, so far at least, is common to all humanity and that most physicians do not consider a disease. 'Curing aging is not an endpoint the federal drug agency would recognize,' Dr. Westphal says dryly. Instead, both men say, they are working to ameliorate the diseases of aging."

Furthermore, up until very recently aging research has been conducted by an extremely conservative research community. In effect, the older half of the community has been active or complicit in suppressing exploration, expansion and application of their work:

https://www.fightaging.org/archives/000728.php
https://www.fightaging.org/archives/000448.php

Thankfully, this cultural roadblock is beginning to melt away, but we are still stuck with a regulatory system that explicitly forbids attempts to extend the healthy human life span. This is nothing short of insanity.

BULK BIOCHEMICAL CHANGES WITH AGING

Some age-related changes are simpler than others - single chemical changes in a widespread, important molecule rather than interrelated alterations in the behavior of complex biological systems. For example, consider the accumulation of glucosepane cross-links in the skin - and the consequences to skin structure and resilience - versus the multifaceted breakdown of the immune system with age. The paper referenced in this Fight Aging! post looks at the contribution of such simpler chemical changes to the age-related failure of elastin in the body:

https://www.fightaging.org/archives/001389.php

"The quantitative evaluation of these processes suggests an approximative upper limit for the elastic properties of the cardio-respiratory system of about 100-120 years, at least, as far as elastin is involved."

"The technologies of slowing and repairing haven't progressed very far at all down the road of what is possible. Yet. But they will - and viewpoints like that in the paper above encourage more people to think in terms of damage and repair. This is important, because that mindset leads to initiatives and results."

"Reversing bulk changes in chemical properties and structure in the body - like the changes that render elastin incapable of its function - is an area in which I would expect to see significant progress sooner rather than later. Once funding and a research community ramps up, that is. This is a situation ideally suited to the present generation of biotechnology: molecules and molecular complexes in state A that you'd rather have in state B - with the complication that your chemical tool for achieving that goal must be safe to put inside people. There are many, many different types of such biochemical changes that we'd like to undo, but each victory is incremental progress, and many research groups can work in parallel."

DISCUSSION

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!

Reason

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LATEST HEALTHY LIFE EXTENSION HEADLINES

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/

More on Predation Versus Longevity (January 11 2008)
http://ouroboros.wordpress.com/2008/01/11/predation-vs-longevity-a-counterexample/
Biology is diversity; while the rule on predation and the evolution of longevity seems to hold for most species, there are always outliers: "mice are low on the food chain and rather likely to meet a bad end; consequently, there’s very little opportunity for genes that enhance longevity to benefit the animal (or even get expressed in the first place). Based on examples of this kind, biologists of aging generally predict that lower extrinsic mortality from predation is a positive influence on the evolution of longevity. Hence, it is surprising that guppies exposed to predation actually appear to live longer (and age more slowly) than similar fish from a similar environment without predators. ... This is an exception to two classical predictions of evolutionary theory: that low extrinsic mortality should be associated with longer life span, and that higher fertility should be associated with shorter life span. Some theorists have tried to accommodate this and other anomalous results within the standard framework, but we argue that the exceptions they carve out do not explain the results at hand. In fact, the findings suggest that population regulation has been selected at the group level, though this is a mechanism that most theorists regard with suspicion."

Pushing Out the Frontiers of Yeast Longevity (January 11 2008)
http://biosingularity.wordpress.com/2008/01/11/10-fold-life-span-extension-reported-in-simple-organism/
As noted at Biosingularity, researchers are greatly improving the degree to which they can extend the life spans of simple organisms: "Biologists have created baker's yeast capable of living to 800 in yeast years without apparent side effects. The basic but important discovery, achieved through a combination of dietary and genetic changes, brings science closer to controlling the survival and health of the unit of all living systems: the cell. ... Longo's group put baker's yeast on a calorie-restricted diet and knocked out two genes, RAS2 and SCH9, that promote aging in yeast and cancer in humans. ... We got a 10-fold life span extension that is, I think, the longest one that has ever been achieved in any organism." It is interesting to see methods that are additive - this result in and of itself is going to spur a great deal of combinatory experimentation in mice over the decade ahead, I'll wager.

Exercise and Calorie Restriction: Both Good (January 10 2008)
http://www.eurekalert.org/pub_releases/2008-01/wuso-elo011008.php
If you want to help yourself live a longer, healthier life, you have to keep up with the basics. From EurekAlert!: "Studying a group of healthy, overweight but not obese, middle-aged men and women, the researchers found that a yearlong regimen of either calorie restriction or exercise increase had positive effects on heart function. Their analysis revealed that heart function was restored to a more youthful state so that during the heart's filling phase (called diastole) it took less time for participants' hearts to relax and fill with blood. ... By the end of the yearlong study, both the calorie restriction and exercise groups of volunteers lost 12 percent of their weight and 12 percent of their body mass index (BMI), a measurement considered to be a fairly reliable indicator of the amount of body fat. In both groups, participants' hearts responded to this weight loss by gaining the ability to relax more quickly, recovering some of the elasticity characteristic of younger heart tissue. Those in the calorie restriction group achieved slightly more reduction of heart stiffness. ... By looking at filling function in healthy, non-obese [people], the researchers in the current study were able to understand in more detail how normal hearts react to moderate weight loss."

Update on Bear Biochemistry and Osteoporosis (January 10 2008)
http://online.wsj.com/public/article/SB119983481583876129.html
The Wall Street Journal looks at ongoing research into the secrets of bear biochemistry: "Why don't bears suffer from osteoporosis during hibernation, he asked himself during one wilderness encounter nearly a decade ago? Even a few weeks of inactivity for humans, and most animals, are enough to soften and weaken bones. But bears snooze as much as six months a year and wake up robust and ready to rumble. ... bears have a uniquely potent form of a substance called parathyroid hormone, which helps maintain bones. The ursine version of the substance spurs bone growth when it normally wouldn't occur, offsetting the deterioration that one would expect for a bear snoozing away in the woods. Dr. Donahue's group has sequenced the gene for the bear parathyroid hormone and has had a small amount of it made synthetically. He's applied for a government grant to fund the lab's efforts to insert the gene into bacteria and coax them to produce the substance." It's a fair way from basic research such as this to accurate, safe control over human biochemistry - but that is the end goal.

Alzheimer's and TNF-Alpha (January 09 2008)
http://www.sciencedaily.com/releases/2008/01/080109091102.htm
ScienceDaily summarizes a recent demonstration of the dynamic role TNF-alpha plays in Alzheimer's disease. The full PDF paper is available for those who care to dig deeper. "Normally, TNF finely regulates the transmission of neural impulses in the brain. The authors hypothesized that elevated levels of TNF in Alzheimer's disease interfere with this regulation. To reduce elevated TNF, the authors gave patients an injection of an anti-TNF therapeutic called etanercept. Excess TNF-alpha has been documented in the cerebrospinal fluid of patients with Alzheimer's. The new study documents a dramatic and unprecedented therapeutic effect in an Alzheimer's patient: improvement within minutes." From the abstract: "In addition to its pro-inflammatory functions, TNF-alpha has recently been recognized to be a gliotransmitter that regulates synaptic function in neural networks. TNF-alpha has also recently been shown to mediate the disruption in synaptic memory mechanisms, which is caused by beta-amyloid and beta-amyloid oligomers." You might recall demonstrations in 2006 and 2007 showing mice full of beta-amyloid, but suffering no symptoms of neurodegeneration due to key changes in the mechanisms by which amyloid affects the brain.

Stem Cell Medicine: Less Regulation, More Progress (January 09 2008)
http://www.abcnews.go.com/print?id=4109559
Less regulation means greater progress. In medicine, that truism is demonstrated year after year in veterinary science. From ABC News: "You can see that the edges of the bone are very worn away. They're not nearly as smooth ... Facing the possibility of a shortened life for Hunter, the Rihas were considering a $10,000 hip replacement when the doctors offered something new, different and much less expensive. For only about $2,500, they could treat Hunter with his own stem cells, the healing and regenerative cells that live in both humans and animals. ... This is an excellent in-between that may mean he may never need a total hip ... In the race to perfect 'regenerative medicine,' stem cell therapy for animals is ahead of treatment for humans because it is not so strictly regulated. It's not experimental - it's here. ... There are no side effects and no problems with rejection, because the patient is also the cell donor. ... I don't see any reason why humans aren't doing it." There is no reason, beyond wasteful, damaging government restrictions and government employees more interested in pointless rules than progress, health and the lives of others.

Eyeing Progress at Sirtris (January 08 2008)
http://www.telegraph.co.uk/earth/main.jhtml?xml=/earth/2008/01/07/scidiab107.xml
This Telegraph piece is a good summary of the present direction at Sirtris Pharmaceuticals - producing more effective sirtuin activating drugs, and commercializing them as diabetes treatments. From the company: "A strong trend to lowering glucose and statistical significance in improving insulin sensitivity showed the benefits of activating the sirtuin anti-ageing genes to treat a disease of ageing. It is important to note that glucose and insulin are two of the key markers of ageing, and in this study, we seem to be having a positive effect on both. ... SRT501 may represent a promising treatment option for these [diabetic] patients. We look forward to obtaining the results from our other Phase 1b clinical trial and the results from our Phase 2a clinical trial later this year. ... If all goes well, SIRT1 activator drugs could be available on the market as early as 2012 or 2013." This is all a small step in a less productive direction, really, when viewed in the grand scheme of things. Regulators won't permit commercialization of therapies to tackle aging itself, hence the focus becomes patching up preventable, avoidable diseases - rather than doing something truly groundbreaking.

Working Towards Control of Muscle Growth (January 08 2008)
http://www.eurekalert.org/pub_releases/2008-01/cp-nii010208.php
Progressive loss of muscle with age is a problem, and a number of lines of research show promise in engineering a way around that. Here, EureAlert! notes another possible path: "a transient and local rise in an inflammatory signal, the cytokine known as interleukin-6 (IL-6), is essential for the growth of muscle fibers. The findings offer the first clear mechanism for the stem cells' incorporation into muscle and the first evidence linking a cytokine to this process ... As we learn more about how muscles grow in adults, we may uncover new methods for restoring lost muscle mass in the elderly and ill ... IL-6 was produced both within myofibers and in their associated satellite cells, leading to muscle growth. In contrast, the muscles of mice lacking IL-6 did not show any significant increase in size after several weeks of overloading. The researchers also showed that IL-6 exerts its effects by inducing the proliferation of satellite cells. ... Treatments could be designed to compensate for or block the pathways leading to muscle loss. In muscles that have already lost mass, you might also be able to stimulate muscle growth."

Calorie Restriction in the Times Online (January 07 2008)
http://www.timesonline.co.uk/tol/life_and_style/health/article3121926.ece?print=yes
The Times Online is running an article on calorie restriction (CR) and its practitioners - suffering somewhat from the outsider looking in, per usual. "The problem with CR studies is that the majority have been done in short-lived animals like rats. Primates are more difficult to study as less is known about their nutrition and they live relatively long lives. A rhesus monkey can live 40 or 50 years in captivity, even without CR. ... Comparing the mice, monkey and human studies should give him a clearer picture of how, and if, CR works in humans. ... It's advantageous for mice to switch to a high reproductive gear in the season of plenty. Come winter it is better to switch that off because you don't want a lot of offspring when you have less food, body fat and energy ... In the wild, CR - a lack of food - helps animals get through winter so they can breed in spring. ... CR seems to switch down that sex drive (anecdotally more so in men) [and] diverts the body's energies elsewhere into a broad set of maintenance activities. The byproduct may be life extension."

The Years of Difference (January 07 2008)
http://www.eurekalert.org/pub_releases/2008-01/plos-fhb010708.php
EurekAlert! summarizes the results of a recent PLoS Medicine study: "People who adopt four healthy behaviours - not smoking; taking exercise; moderate alcohol intake; and eating five servings of fruit and vegetables a day - live on average an additional fourteen years of life compared with people who adopt none of these behaviours ... After factoring in age, the results showed that over an average period of eleven years people with a score of 0 - i.e. those who did not undertake any of these healthy forms of behaviour – were four times more likely to have died than those who had scored 4 in the questionnaire. Furthermore, the researchers calculate that a person who has a health score of 0 has the same risk of dying as someone 14 years older who had scored 4 in the questionnaire (i.e. someone engaging in all four healthy forms of behaviour)." The cost of harming yourself, or indeed even of just failing to take care of the health basics could be very large indeed, given the prospects for the repair of aging in the future. Ten years might be the difference between living to benefit from healthy life extension technologies, or missing that boat entirely.

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