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Longevity Meme Newsletter, February 12 2007

LONGEVITY MEME NEWSLETTER
February 12 2007

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

- UK Radio Podcast, Aubrey de Grey Interview
- Great Progress Made, Much More to be Accomplished
- Discussion
- Latest Healthy Life Extension Headlines

UK RADIO PODCAST, AUBREY DE GREY INTERVIEW

You'll find links to a podcast UK radio interview with biomedical gerontologist Aubrey de Grey in a post from the past week at Fight Aging!:

https://www.fightaging.org/archives/001115.php

"What would you do if you could live forever? The question may not be as far fetched as it sounds, according to Cambridge University biologist Aubrey de Grey. He believes that people alive today will live beyond 1000 thanks to medical advances to prevent ageing."

That journalist's "will" should be replaced by the engineer's "could, if we all get our act together" - which is much what you'll find if you choose to follow up and read de Grey in his own words. You can find more thoughts on timescales, chances and the needed work back in the Fight Aging! archives:

https://www.fightaging.org/archives/000608.php
https://www.fightaging.org/archives/000756.php
https://www.fightaging.org/archives/000817.php

GREAT PROGRESS MADE, MUCH MORE TO BE ACCOMPLISHED

The end of January marked three years of the Fight Aging! blog, and I took the occasion to note that advocates for greater funding of longevity science - and plausible, rapid progress towards the first true rejuvenation medicine - have made great strides in that short span of years:

https://www.fightaging.org/archives/001116.php

"Fight Aging! commenced around the time I first started volunteering with the Methuselah Foundation - back when the pledge fund stood at $10,000, and folk were drumming up support and donations from the healthy life extension advocates of the transhumanist community. Pledges today have topped $8.5 million dollars, and that seems like a big deal in terms of progress. The environment for debate on healthy life extension has changed greatly for the better in the past few years, and I don't think it's just the incremental advance of science, nor the many new faces who swell the ongoing conversation. This is the start of a thaw, a sea change in attitudes that will continue and reinforce itself."

At the same time, much of what I said back in 2004 on the need for progress in specific areas is just as true today. A vast sea of untapped resources and people unaware or uncaring of the prospects for real progress in longevity medicine over the next few decades remains to be accessed - no one has yet cracked the code for rapidly generating widespread understanding and support of meaningful anti-aging research.

https://www.fightaging.org/archives/001117.php

"In the world at large, most people still think of living longer through medicine as being older for longer, not being younger for longer - and they knee jerk in rejection. Most people believe that 'anti-aging science' is supplements, hucksters and flashy nonsense from cosmetics companies, and that real rejuvenation is impossible - or so far away as to be unworthy of consideration. Many people believe that overpopulation is a serious threat, that pollution will outrun technology, that the future is one of rust and poverty, rather than a golden age of technology; they see no worth in living into such a future. Many people believe they cannot affect or change the way the future unfolds. Many people have so armored themselves with a mindset of acceptance against the ugly realities of age-related suffering that they are unwilling to even talk about the subject, or consider any form of change, even for the better.

"This is essentially no different today than it was ten years ago. The changes for the better made in a few years of work are small compared to the whole, a stream feeding into a sea. But it's a start, and it's growing."

So we keep hammering away at the problem; it's a very human problem, rather than one of technology per se. It's clear that the biotechnology revolution has enough steam to get us wherever we desire to go, given the funding, some number of years and the will to action. No, the issue is that enough people have to realize that greatly extended longevity is in fact possible comparatively soon, realize that science and biotechnology are how it can be accomplished, and decide to support that goal. Then it will begin to happen in earnest.

That was an imposing undertaking ten years ago, and it's little less of an imposing undertaking today - but we're getting there. It's been done before; for cancer, AIDS, Alzheimer's, diabetes, and so forth - so it can be done again, for the roots of all age-related degeneration. If you don't take the first steps, the journey will certainly never be done.

https://www.fightaging.org/archives/000975.php

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

Founder, Longevity Meme

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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/

Linking Calorie Restriction and Neuroprotection (February 11 2007)
http://www.pmid.us/17240074
This paper examines a mechanism to link the practice of calorie restriction to greater resistance to age-related neurodegeneration via slowing the rate of cellular damage caused by your own mitochondria: "Dietary protocols that increase serum levels of ketones, such as calorie restriction and the ketogenic diet, offer robust protection against a multitude of acute and chronic neurological diseases. The underlying mechanisms, however, remain unclear. Previous studies have suggested that the ketogenic diet may reduce free radical levels in the brain. Thus, one possibility is that ketones may mediate neuroprotection through antioxidant activity. ... Ketones also significantly decreased mitochondrial production of reactive oxygen species." This is a similar mechanism to that associated with melatonin - reduce the ongoing rate of damage through oxidative stress due to free radicals, such as reactive oxygen species. Like melatonin, however, calorie restriction is a crude tool indeed for impacting health and life span - we move the whole interconnected, poorly-understood system towards a change for the better, so far as we can tell. But the prospect of doing far better for our future longevity is right in front of our noses - all we have to do is to support and fund the research.

AMPK, Aging and Exercise (February 11 2007)
http://news.bbc.co.uk/2/hi/health/6334899.stm
From the BBC: researcher "compared the skeletal muscle of three-month-old rats and two-year-olds. They found that a process called AMP-activated protein kinase (AMPK) slowed down in the older animals. AMPK's role in skeletal muscle is to stimulate the body to burn off fat and to fuel cells, via the production of mitochondria - cells' power sources. ... a person would have to work harder when trying to maintain the same benefits from exercise as they did when they were young. AMPK activity in our skeletal muscle is probably a good thing because it activation stimulates glucose uptake, increases fat oxidation [fat burning], and promotes mitochondrial biogenesis [production]." As Randall Parker points out, this looks a lot like an evolutionary adaptation to minimize damage caused by increasing numbers of cells taken over by age-damaged mitochondria - which has the effect instead of making insulin resistance, type 2 diabetes and age-related muscle loss (sarcopenia) the order of the day. Expect to hear more on this in the next few years as scientists determine where AMPK fits within the hierarchy of cause and effect in aging.

Betting on Medical Progress (February 10 2007)
http://www.aleph.se/andart/archives/2007/02/banking_and_insuring_stem_cells.html
A perspective on some areas of modern medical research and development from Anders Sandberg: Branson's venture into stem cell banking "may turn out more useful than we could possibly think today because of advances in regenerative medicine that enable new uses of stem cells. It could also become totally obsolete if the advances go so far that normal cells can be turned into stem cells. ... This raises the interesting issue of gambling on future medical advances. Cryonics already does this in a spectacular and controversial fashion. Storing stem cells is a less radical gamble (we already know they can be useful for some things, but we don't know if they will ever prove useful for our particular maladies). ... Might we use known areas of medical progress to bank on things that are currently not useful but will be useful in the future? ... Maybe we should start documenting our healthy metabolome, kineome and proteome when we are young, somehow. Having a backup never hurt." If investment, competition and a lack of oppressive regulation can drive the cost low enough, all these things would be a bet worth taking.

Crude Tools (February 10 2007)
http://ouroboros.wordpress.com/2007/02/09/melatonin-as-an-anti-aging-therapeutic-for-the-brain/
A post on the applications of melatonin from Ouroboros is a good illustration of just how crude are the tools available to us today. It's like having a complex machine and trying to keep it running for longer by hitting it with a hammer at various points to jog the components. Entire branches of the scientific community are devoted to figuring out where best and how hard to hit the machine; it used to be a matter of trial and error, but now is moving towards better understanding how the components fit together. "Animal and cell culture models of several [neurodegenerative] disorders have benefited from the application of melatonin. The mechanisms underlying the neuroprotective properties of melatonin are likely to involve activation of specific melatonin receptors. This can lead to modulation of transcription factors and consequent altered gene expression, resulting in enhancement of antioxidant enzymes and downregulation of basal levels of inflammation. Melatonin has potential utility both in slowing normal brain aging and in treatment of neurodegenerative conditions." The greatest advance that stems from modern biotechnology will be the ability to move beyond the hammer approach - and melatonin is very much a hammer approach - to precisely interact with the components of the machinery rather than reaching into the rack of blunt implements.

Recent Alagebrium Research (February 09 2007)
http://www.pmid.us/17278974
Alagebrium, or ALT-711, is an AGE-breaker - a class of compound designed to break up the advanced glycation endproducts (AGEs) that contribute to some types of age-related degeneration. "Arterial stiffening and endothelial dysfunction are hallmarks of aging, and advanced glycation endproducts (AGE) may contribute to these changes. We tested the hypothesis that AGE crosslink breakers enhance endothelial flow-mediated dilation (FMD) in humans and examined the potential mechanisms for this effect. ... Alagebrium enhances peripheral artery endothelial function and improves overall impedance matching. Improved endothelial function correlates better with reduced vascular fibrosis and inflammation markers than with vessel distensibility. AGE-crosslink breakers may reduce cardiovascular risk in older adults by reduced central arterial stiffness and vascular remodeling." Unfortunately, despite promising animal studies, results in people have not been unambiguously positive: it is probably the case that alagebrium targets a type of AGE that is common in old animals, but not in old people. AGE-breakers are a serious branch of research, but we need to move past alagebrium as anything other than an illustrative example, and on to the fruits of more advanced biotechnology.

On "Human Dignity" (February 09 2007)
http://www.reason.com/news/show/118608.html
(From Reason Online). Those who would work to ensure we all age, suffer and die wave the banner of "human dignity" - a twisted construct of tortured meaning in their hands, as any rhetorical tool must become in the service of herding millions to their graves: "That deeply felt lack and limitation, of which Kass speaks, is what motivates scientists to develop new treatments not only to rescue people from the ordinary degradations of disease and the slow loss of vitality that comes with aging, but it is what also inspires them to conjure the new technologies that will enable people to flourish. Transhumanists argue for allowing people to choose the good of augmented capacities such as stronger immune systems, more agile bodies, sharper minds, greater powers of self-control, and radically longer lives. Instead of being degraded, people will be liberated to perfect as never before arts and crafts, song and story, noble deeds and customs, fine character, the search for wisdom, and yes, even a reaching for the eternal and the divine. The pursuit of mastery over pitiless nature will not only expand and enlarge human capabilities, but it will also expand and enlarge true human dignity. ... Surely the salient lesson we learn from Brave New World is that we must guard against tyranny, not against technological progress."

More on Mitochondria, Gender and Aging (February 08 2007)
http://www.physorg.com/news90156140.html
Via PhysOrg.com, more on possible biomechanisms for gender differences in longevity: "While both parents contribute to their offspring's cellular genetic inheritance, only the female passes on the mitochondrial genome to the next generation. Why, and how, this asymmetrical inheritance happens is not clear, but Tower thinks understanding it may be key to understanding sex differences in aging. ... Mitochondria play a key role in regulating the programmed cell death pathway, or apoptosis. In flies and humans, apoptosis works during normal embryonic development and sexual differentiation, sculpting the body by killing unwanted cells. But the cell death pathway, in which the p53 gene is a central player, also appears to malfunction more frequently over an organism's lifetime, thereby contributing to aging and aging-related diseases like Parkinson's. This might happen more often or differently in males, Tower speculates, leading to a shorter life span. Tower's far-reaching model leads to 'a list of predictions,' which his lab has already started testing in experiments with Drosophila. One that he's particularly interested in following up on is the idea that the human Xist gene may control sex determination and be very much involved in regulating human life span."

On the Culture of Instant Gratification (February 08 2007)
http://www.slate.com/id/2158975/pagenum/all/
I think the recent article on calorie restriction with optimal nutrition (CRON) in Slate gives more insight into the damaging culture of instant gratification - and instant results, or else - than anything else. "[Mary] Robinson told me how she came to adopt the CRON life six years ago. ... She joined the Calorie Restriction Society and wrote a computer program to track everything she ate and its nutritional value. It has vastly improved her health. Robinson was in a study of CRON followers done by Dr. Luigi Fontana at Washington University School of Medicine. Fontana found that the CRON adherents - many of whom, like Robinson, had been formerly pudgy - now had arteries as efficient as fire hoses and blood pressure readings like those of 10-year-olds. ... Is CRON crazier than having a doctor suck out your fat, or staple your stomach? Is it crazier than a world in which a drug company is looking to market a product to temporarily eliminate people's sense of taste and smell so they will lose weight? ... But can someone without any notable will power - me - stay on a CRON diet? I decided to try CRON for two months, but it's past that now and I'm still avoiding seconds and skipping my late-night snack. CRON was supposed to do much for me that it hasn't." All worthwhile results require a little effort and persistence.

Linking Tau and Amyloid Beta in Alzheimer's (February 07 2007)
http://www.virginia.edu/uvatoday/newsRelease.php?id=1435
Tau and amyloid beta are implicated in the mechanisms of Alzheimer's disease; here researchers look into why we see both: "two kinds of abnormal structures accumulate in the brain: amyloid plaques and neurofibrillary tangles. The plaques contain fibrils that are made from protein fragments called 'beta-amyloid peptides.' The tangles also are fibrous, but they are made from a different substance, a protein called 'tau.' ... researchers found a deadly connection between beta-amyloid and tau, one that occurs before they form plaques and tangle ... We think we've found one of the seminal cell biological events in the pathogenesis of Alzheimer's and if we can figure out all of the steps in the process and understand each player at every step, it will represent many potential new drug targets for Alzheimer's therapy. Our paper defines one of the earliest events that causes neurons to die in both early-onset familial Alzheimer's and late-onset Alzheimer's disease. We believe this is the first evidence for the long elusive 'missing link' between amyloid and tau in Alzheimer’s disease."

What Early Medical Nanorobots Will Look Like (February 07 2007)
http://www.eurekalert.org/pub_releases/2007-02/cmu-cmr020707.php
Scientists will be designing and mass-producing medical nanorobots from carbon feedstock some decades from now, so as to directly manipulate biochemistry to cure and prevent disease, wear and tear, and ultimately aging itself - but we'll have to get the whole molecular manufacturing technology base sorted out for that. Earlier than this, it seems likely that the first medical nanorobots (well, microrobots in this case) will be highly modified or even completely artificial cells. Why ignore the working blueprint that's right in front of you, after all? Via EurekAlert!: "Our proposal is to use naturally available molecules to create pseudo-cell factories where we create a super artificial cell capable of targeting and treating whatever is ailing the body. The human cell is like a bustling metropolis, and we aim to tap the energy and diversity of the processes in a human cell to help the body essentially heal itself. ... Understanding both the nature of a cell as an independent unit and its role in the life processes of larger organisms is crucial in our quest to duplicate the molecular units which form the building blocks of the cell and its parts. We see this development of artificial cells as a building block for a variety of new and exciting therapeutic approaches."

Evolutionary Tradeoffs: Stem Cells and Cancer (February 06 2007)
http://ouroboros.wordpress.com/2007/02/06/devils-bargain-tradeoffs-between-stem-cell-maintenance-and-tumor-suppression/
From Ouroboros, a look at where evolution has left us in the aging and longevity stakes: "An emerging theme in biogerontology is the idea that lifespan may be determined by the balance between regeneration and tumor suppression. Long-term tissue health demands that damaged and dead cells be replaced, but unlimited replicative potential poses the risk of cancer. Therefore, to prevent tumors, organisms must accept a decrease in regenerative capacity. ... How direct is this connection? In an indirect model, differentiated cells are the initiatiors of tumor growth. p53 limits stem cell proliferation, which in turn decreases the rate of production of new differentiated cells. Fewer cells available to undergo neoplastic transformation means fewer cells available to initiate tumors, with the unfortunate consequence that tissues requiring new cells to maintain homeostasis must go begging. In a direct model, tumor suppressor activity decreases the number of stem cells that might become dysregulated and transformed into cancer stem cells, a relatively new concept in cancer biology." Evolution got us this far, and now its up to us to carry the ball forward to greater longevity through advanced biotechnology.

Sign Up For SENS3 (February 06 2007)
http://blog.methuselahfoundation.org/2007/02/registration_and_abstract_subm.html
From the desk of biomedical gerontologist Aubrey de Grey: "registration and abstract submission are now open for the third Strategies for Engineered Negligible Senescence (SENS) conference, to be held at Queens' College, Cambridge, England on September 6th-10th 2007. The early registration and abstract submission deadlines are both June 15th. ... The preliminary program already has 48 confirmed speakers, all of them world leaders in their field. As for previous SENS conferences, the emphasis of this meeting is on "applied gerontology" - the design and implementation of biomedical interventions that may, jointly, constitute a comprehensive panel of rejuvenation therapies, sufficient to restore middle-aged or older laboratory animals (and, in due course, humans) to a youthful degree of physiological robustness ... In addition, there will be at least a dozen short talks selected from submitted abstracts, as well as poster sessions each evening. Authors of short talks and posters will, like the invited speakers, be invited to submit a paper summarising their presentation for the proceedings volume, which will be published in the high-impact journal Rejuvenation Research early in 2008."

Learning From Werner Syndrome (February 05 2007)
http://www.eurekalert.org/pub_releases/2007-02/si-ffl020107.php
The rare accelerated aging (or progeroid) conditions have a lot to teach us about "normal" aging, as illustrated by this EurekAlert! piece: "Patients with Werner Syndrome manifest signs of aging, such as skin wrinkling, baldness, or hair graying, in their teens. Most die in their 40's or 50's due to a predisposition to diseases like cancer. ... Cancer is almost always related to chromosomal instability. If telomeres are lost on individual chromosomes, then chromosomes are not protected and can fuse with other nonprotected chromosomes. Then when cells divide, chromosomes randomly break, leading to genome instability ... The lack of a single protein (WRN) [mutant or nonfunctional in Werner Syndrome] induced loss of some telomeres, leading to a premature cellular growth arrest ... When we put telomerase into cells [it] fixed the defect by elongating short telomeres seen in Werner Syndrome cells ... We study this disease because it is an excellent model for aging, and we show here a direct relation between aging, telomere loss, and cancer occurrence. I predict that cancer in older people has precisely the same basis as that seen in Werner Syndrome patients. That is why this was such a satisfying study."

The Myth of Antioxidants (February 05 2007)
http://www.newscientist.com/article/mg19125631.500
The New Scientist looks at the myth of antioxidants: that piling them into your system is necessarily a good thing. "Since the early 1990s scientists have been putting these compounds through their paces, using double-blind randomised controlled trials - the gold standard for medical intervention studies. Time and again, however, the supplements failed to pass the test. True, they knock the wind out of free radicals in a test tube. But once inside the human body, they seem strangely powerless. Not only are they bad at preventing oxidative damage, they can even make things worse. Many scientists are now concluding that, at best, they are a waste of time and money. At worst they could be harmful." Mouse studies have shown that carefully directing antioxidants to the cellular mitochondria extends healthy life span on the order of 20-30% - a fairly complex feat of biochemical engineering that no presently available pill can match. Those studies further showed no benefit from the same antioxidants sent elsewhere in mouse biochemistry. Haphazardly throwing chemicals at a very complex problem and hoping for the best does not have the best record of success - when that's all you can do, you do it, but we can do better now.

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