Fight Aging!

LONGEVITY MEME NEWSLETTER
January 22 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

- Rapid, Welcome Growth in The Three Hundred
- Thinking About Cancer Research
- The Skeptical View of Cancer Stem Cells
- Discussion
- Latest Healthy Life Extension Headlines

RAPID, WELCOME GROWTH IN THE THREE HUNDRED

Looking back over the past six months, growth in the ranks of the Methuselah Foundation's Three Hundred has increased noticeably, no doubt spurred by Peter Thiel's matching grant and high profile donation. We've seen a couple of major foundations, a successful young poker player, folk from the established healthy life extension community and welcome newcomers - all stepping up to further illustrate that everyone can make a difference to the speed with which real technologies of rejuvenation are developed.

You can view donors and their comments at the Mprize website:

http://www.mprize.org/index.php?pagename=threehundredlist

Learn more about The Three Hundred by following this link:

http://www.mprize.org/index.php?pagename=thethreehundred

THINKING ABOUT CANCER RESEARCH

I've spent a fair amount of time discussing cancer research at the Longevity Meme and Fight Aging! in the past few months: cancer, the result of age-worn or otherwise broken biochemistry run amok, is one of the bolded line items to be defeated if we are to win out over aging. Like the repair of the aging brain, reengineering humanity to remove the possibility of cancer is likely to be "hard" in comparison to the "easy" jobs like building replacement organs - from what we know today, even the paths of least resistance will be tough going:

https://www.fightaging.org/archives/000497.php

On the other side of the coin, cost-effective early detection methods and cures for individual outbreaks of cancer do look to be widely available within the next ten to twenty years. How far can we ride that horse while our lives are being lengthened by other means?

https://www.fightaging.org/archives/001100.php

"The risk of cancer in any tissue increases with age - and as for most failing machines, quite dramatically so in later life. This stems from underlying changes in biochemistry and the simple rules that determine failure rates in machinery based on gradual wear in component parts - possibly the shortening of your telomeres, possibly damage to stem cells, possibly something else, possibly all of the above. Is it good enough to have a good after-the-fact cure on hand when the risk of occurrence is increasing enormously with each passing year? Is there a point past which a good therapy is just overloaded by sheer weight of new cancer bursting from your cells, and where does that point occur?"

THE SKEPTICAL VIEW OF CANCER STEM CELLS

If you've been following the popular science press of late, you'll no doubt know that the intersection of cancer and stem cell research is generating great excitement in both well-funded research communities. It is plausible that most cancers can be quelled by targeting clearly identifiable stem cells. It is even possible that most cancers arise from a small set of changes, tiny malfunctions in stem cells - and could thus be averted even prior to the first cell becoming cancerous:

https://www.fightaging.org/archives/2007/01/the-source-of-cancer/

With this in mind, I should point your attention to an outline of a skeptical view of the prospects for effective cancer cures arriving from this direction. Nothing is easy in biochemistry! See this Fight Aging! post for more:

https://www.fightaging.org/archives/001095.php

Given the present rate of progress and level of funding, I think it unlikely that any debate over the effectiveness of identifying and targeting cancer stem cells will remain unsettled past 2012, five years from now. The first therapies based on present day approaches in the laboratory should be somewhere in late trials by that time.

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/

Sirtris and the Third Rail Illustrated (January 21 2007)
http://money.cnn.com/2007/01/18/magazines/fortune/Live_forever.fortune/
One of the folk working on mitochondrial repair via protofection has said "'The cure for aging' is the instant-death third rail of grantsmanship and we stay away from it." It doesn't matter how relevant your work is to rejuvenation via the slowing or repair of age-related damage, the conservative funding and regulatory culture wants to hear you disclaim any intent in that direction. Sadly, this is only now beginning to slowly change - but where the money is in full flow, this mindset remains well in evidence. Via a Fortune profile piece on Sirtris and the science behind its CR mimetics: "he's determined to avoid any whiff of 'fountain of youth' hype - specifically, of giving the impression that Sirtris is a bunch of flakes chasing miraculous elixirs, which is the kiss of death for a startup trying to raise millions of dollars from hard-nosed money managers. He spends a lot of time explaining that his company is working to cure diseases of aging, not to cure aging itself. There's a difference, especially in the minds of regulators, who view aging as part of the human condition, not an illness warranting treatment." These are the chains of the mind that must be broken if the promise of modern biotechnology can be fulfilled, and our healthy lives greatly lengthened.

The Strange Mix of Attitudes Towards Longevity (January 21 2007)
http://www.sciencedaily.com/releases/2007/01/070116131540.htm
The popularity in the press of articles explaining a bonus of an extra year here and a year there to your life span (through some mundane circumstance or lifestyle choice) stands in stark contrast to the comparative unpopularity of articles discussing the serious prospects of engineering additional decades - and then centuries. People are fascinated and eager to read about additional longevity, but at the same time shy away from the very same thing. The frivolous is called from the rooftops, the serious dismissed. It is all very strange; a puzzle waiting to be cracked by those engaged in healthy life extension advocacy. "The average life span for this group was just over 76 years. Winners of the Nobel Prize were found to live 1.4 years longer on average (77.2 years) than those who had 'merely' been nominated for a prize (who lived on average for 75.8 years). When the survey was restricted to only comparing winners and nominees from the same country, the longevity gap widened even more by around another two thirds of a year on average. ... Status seems to work a kind of health-giving magic. Once we do the statistical corrections, walking across that platform in Stockholm apparently adds about 2 years to a scientist's life-span. How status does this, we just don't know."

Acknowledge the Risks and Limitations (January 20 2007)
http://www.webmd.com/content/Article/131/118059.htm?printing=true
The need for an answer now has a way of bringing people to willfully blind themselves to the realities of uncertainty and risk. This is a familiar sight in that part of the "anti-aging" marketplace that attempts to manipulate common physiological aspects of health by the brute-force application of hormones - pouring fuel on the fire and praying it burns the way you want, in other words. "Roughly 2.4 million prescriptions for testosterone were filled in the U.S. in 2004 -- more than twice the number filled just four years earlier ... the benefits of boosting testosterone levels in otherwise healthy aging men experiencing natural declines in hormone levels are not as well understood. ... Patients and their physicians should be able to make therapeutic decisions with a clear idea of what the risks and benefits are, but in this case that isn't possible. There is still a lot of uncertainty about this treatment ... We have a situation where physicians and patients are essentially in the same boat. Neither is fully informed about testosterone therapy, because the long-term research just hasn't been done."

How To Fund Your Cryopreservation (January 20 2007)
http://www.alcor.org/BecomeMember/sdfunding.htm
Alcor, a cryonics provider, recently posted a helpful overview of the way in which folk of ordinary means fund indefinite low-temperature storage following death, to await future technology capable of repairing the damage of aging and disease. "The following four funding methods are currently accepted by Alcor for new applicants ... 1. Life Insurance. Used by the vast majority of current Alcor members, this is the most typical funding arrangement because it is affordable on a day-to-day basis. Alcor is designated as both the beneficiary and owner of the life insurance policy (revocable if membership terminated) ... 2. Prepaid - Cash or Equivalent ... 3. Trusts. All trusts involve some form of fees to the oversight trust company. Some applicants may perceive a potential advantage of trust funding, as it introduces third-party involvement in the trust company, which pays Alcor after the terms of your contract with Alcor have been satisfied. ... 4. Annuity. An annuity is a 'savings plan with a life insurance company.' Funds are reallocated from other accounts to establish an annuity. An annuity can provide the same level of certainty of funds being available as a life insurance policy."

More On Funding Embryonic Stem Cell Research (January 19 2007)
http://www.reason.com/news/show/118069.html
By way of following up on a recently noted article on funding for embryonic stem cell research, here are comments by Ronald Bailey from Reason Magazine: "Instead of being modeled on drug development, perhaps embryonic stem cell research will follow a development path more like that blazed by researchers in assisted reproduction. Rather than being hampered by a paucity of federal research funding perhaps embryonic stem cell research will flourish just as research on assisted reproduction techniques (ART) has. Arguably in vitro fertilization research has proceeded rapidly because of, not in spite of, essentially no federal funding. ... Without intrusive federal oversight and regulation IVF researchers have been able to deploy new techniques such as intracytoplasmic sperm injection, pre-implantation genetic diagnosis, and sperm sorting for sex selection very shortly after they have been developed. Research has stopped in promising areas of ART only when the Feds decide to get involved." It should be no surprise that work is more effective per dollar spent when the funders have a far greater, pressing interest in the outcome, and when there is less regulation to raise costs to no good end.

Tackling Type 2 Diabetes Yourself (January 19 2007)
http://www.eurekalert.org/pub_releases/2007-01/bmj-lce011907.php
A reminder via EurekAlert! that type 2 diabetes is one age-related disease that you have a lot of control over: "Changing to a healthier lifestyle appears to be at least as effective as taking prescription drugs in reducing the risk of developing Type 2 diabetes ... [Researchers] found that lifestyle changes, e.g. switching to a healthier diet and increasing exercise to be at least as effective as taking prescription drugs. On average, lifestyle changes helped to reduce the risk of developing type 2 diabetes by around half. Lifestyle changes were also less likely to have adverse side-effects. However, the researchers say that both lifestyle changes and prescription drug taking must be sustained in order to prevent the development of Type 2 diabetes." Neglecting basic good health practices has dire consequences on your life span, quality of life and bank account contents. Exercise, eating sensibly, keeping the weight off and dropping bad habits are nothing new - it's not rocket science. Why not make more of an effort to avoid the avoidable and raise your chances of being healthier for longer?

Change Versus Suffering and Death (January 18 2007)
http://www.opednews.com/articles/genera_jon_faul_070114_science__26_ponce_dele.htm
Here, via OpEdNews.com, is another illustration of the degree to which people see change as a terrible thing, the counterweight when discussing healthy life extension. We hear speakers weighing death and suffering for billions - versus those billions living in good health to see and bring about change - as a choice that requires thought. Amazing; but human psychology is indeed exceptional in ways both good and bad. "It's because of our abbreviated lives that we struggle to fit all the things we want to do, into the little time there is to do them. Bitterness, the acute sense of failure that overtakes so many, results because of nothing more complicated than the repetitious experience of 'That's all. Times up,' as the carny opens the gate on your tilt-a-whirl before you're ready to get off. When science over-runs everything we thought we knew, our Gods, our institutions, all of our notions of governments before and since, even the ethical and moral regards we see as our values, the adjustment humanity will be forced to make will be the most traumatic, but bitter-sweet it has ever suffered." This is just silly and overwrought - people will be people whether they are 20, 80, or hundreds of years old. What "trauma" could possibly match the billion deaths by aging that take place every two decades?

Those Who Want To Age and Die (January 18 2007)
http://commentisfree.guardian.co.uk/edward_pearce/2007/01/post_926.html
(From the Guardian). An odd and sometimes guarded, inward-looking lot, the folk who want to die much younger than future technology could enable. Sighing about boredom here, about approaching change there - even understanding that a longer life would be a longer span of youth, and that death by aging (left unmentioned) is a horror of frailty and suffering, they'd rather anything but live longer. "It would be like Gilbert's account in Patience of a toffee glut. 'We adore toffee; but toffee for dinner? Toffee for tea? Even toffee would become rather tedious.' ... Eternity would surely pall as readily as toffee." Oblivion is a choice of course, and one we should all be free to make. But this sort of flippancy strikes me as the cloak for twice a value judgement: first of the value they give to being alive, and second upon themselves and their merits as a sentient, living being. If you'd rather suffer and die than change and challenge to live in youth, what does that say about what you're bringing to the table? There is the echo of a fear at the bottom of all this: the fear of being offered working anti-aging medicine, using it, and of embracing life for decades more. If you fear that, what is it you really fear? Change, life, or yourself? Just asking.

A Scientist's View on Funding (January 17 2007)
http://dx.doi.org/10.1371/journal.pbio.0050032
From PLoS Biology, a scientist's view of the movement of funds, politics and funding in embryonic stem cell research in the past years: "All this support from states and private donors puts more scientists to work ... With the uncertainty at the federal level [it's] important that the states and private donors are stepping in, 'instead of scientists stepping back and waiting till the policy changes.' ... those hot on the trail of potential cures using stem cells are not about to sit idly by while Washington fiddles. Kerr is hoping for the best in 2007, but he and his California collaborator, Hans Keirstead, are pursuing nonfederal funding 'while we await changes in D. C.' Both are appealing to private philanthropy groups for bridge funding to make sure their work continues. ... Meanwhile the research moves ahead without the centralized control and oversight of the federal government." Can't say I think that last point is a bad thing; expect higher quality and faster progress per dollar spent when research takes place in a much more competitive environment, i.e. when those who hold the purse strings care deeply and personally about results, and misspending has meaningful personal consequences for those who authorize it.

Resveratrol as Antioxidant (January 17 2007)
http://ouroboros.wordpress.com/2007/01/17/resveratrol-as-an-antioxidant/
An interesting thought from Chris Patil of Ouroboros: "The ability to efficiently scavenge reactive oxygen species such as peroxide makes resveratrol protective against oxidative stress ... Thus the cardioprotective effects of resveratrol (or, if you prefer, the wine in a Mediterranean diet) could be mediated not by the regulatory-biological output of a ligand-receptor interaction but rather by an unassisted chemical reaction between small molecules. ... in order for scientists to make the best choices about how to spend our time, it's important to know how a beneficial molecule is exerting its effects. If it's the receptor-mediated outcome that is most desirable, then we should be working on better ligands: molecules that bind more tightly to the proteins that actually generate the relevant output. On the other hand, if the growing family of salubrious natural products turn out to be valuable primarily for their antioxidant activity, then we should be focusing on generating highly effecting antioxidant compounds that can target every tissue and subcellular structure in the body." On the third hand, it seems to me that both are short-termist, considering the presence of far more promising projects aimed at reversing age-related decline.

Disrupting Cancer Stem Cells (January 16 2007)
http://sciencenow.sciencemag.org/cgi/content/full/2007/116/2
A comparatively simple approach to tackling cancer stem cells is reported in Science: "Cancer stem cells are the ultimate source of the tumor, consistently supplying it with new cells. ... Killing these stem cells should allow researchers to hit a tumor where it hurts, yet chemotherapy has proven ineffective as it tends to kill only rapidly dividing cells. ... [researchers] started by comparing cancer stem cells to noncancerous neural stem cells. These neural tissue precursors are concentrated in regions rich in blood vessels. The vessels are lined with endothelial cells, which secrete chemical signals that help stem cell survive. ... after examining over 70 human brain tumors, the researchers found that cancer stem cells were frequently located close to tiny vessels called capillaries. ... Drugs that shrunk the capillaries also caused a significant drop in cancer stem cells and consequently put a damper on tumor growth." Comparatively simple it may be, but this new understanding required the tools of modern biotechnology; as is often the case, greater knowledge leads to better use of older medical technologies.

Searching For the Marks of Stemness (January 16 2007)
http://www.newswise.com/articles/view/526585/
If scientists can identify markers for the errant stem cells that create and sustain cancer, then modern biotechnology can build a targeted therapy to destroy those cells. Hence the search for stemness in cancer, and the modest advance noted at Newswise: researchers "took tumor samples from patients undergoing surgery for head and neck squamous cell carcinoma, including cancers of the tongue, larynx, throat and sinus. Cells from the samples were separated based on whether they expressed a marker on their surface called CD44. ... The cells that expressed CD44 were able to grow new tumors, while the cells that did not express CD44 did not grow new tumors. ... This ability to both self-renew and produce different types of cells is a hallmark of stem cells. ... The percent of cells within a tumor expressing CD44 varied from one sample to the next, with one sample composed of as high as 40 percent of these cells. Studies in other cancer types have found the stem cell population to be smaller than 5 percent. ... The CD44-positive cells contain the tumorigenic cells, but we don't think that's a pure population of cancer stem cells. We still need to drill down further to find the subpopulation of those cells that is the pure version."

The Past of the Future (January 15 2007)
http://www.nanowerk.com/news/newsid=1252.php
A discussion at Nanowerk reminds us that thinkers have been pondering science and the realm of the possible for healthy life extension for quite some time: "In 1769, Diderot, editor of the Encyclopedie, wrote three whimsical essays known as 'D'Alembert's Dream' recounting imaginary dialogues between himself, his friend d'Alembert, a cultured lady friend, and a physician. ... It seems likely that this century will see Diderot's prescience confirmed. In the coming decades, as pharmacology, artificial intelligence, nanotechnology, and biotechnology converge, life spans will extend well beyond a century. Our senses will extend to perceive sights, sounds and sensations beyond our current abilities. We will remember more of our lives, with greater fidelity. We will master fatigue, arousal and attention, and give ourselves more working intelligence. We will have greater control over our emotions, and be less subject to depression, compulsion and mental illness. ... Even if enhancement therapies aren't cheap, their social benefits will generally make them cost-effective. Diderot bids d'Alembert goodnight by saying 'Give a man, I don't say immortality, but only twice his lifespan, and you'll see what'll happen.'"

Replacing An Immune System (January 15 2007)
http://www.eurekalert.org/pub_releases/2007-01/uom-uom011207.php
An impressive demonstration is noted at EurekAlert!: researchers "have successfully used adult stem cells to replace the immune system and bone marrow of mice ... The researchers used multipotent adult progenitor cells (MAPCs), which can be isolated from bone marrow ... Verfaillie and her team isolated MAPCs from mice and expanded them for at least 80 doublings in the lab. They then transplanted the cells into mice that received radiation and thus had no immune system. ... The cells not only survived when transplanted but they completely repopulated the blood system of the mice." Is there a near-term path here towards a viable, safe methodology for replacing an age-damaged and ineffective immune system? Perhaps not, unless another methodology could be used to remove the original system: "Scientists must now understand that mouse MAPCs can make normal blood, and we need to explore how they do it. It is very important to note that MAPCs were not themselves radioprotective, thus they alone could not be used in patients in whom the bone marrow is totally eliminated due to radiation or chemotherapy, but it is still remarkable that they can give rise to blood cells."

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