Fight Aging!

LONGEVITY MEME NEWSLETTER
January 28 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

- Methuselah Foundation Update
- Free Access to Rejuvenation Research
- The Challenges of Long-Term Cryosuspension
- The Destruction Brought On By Excess Fat
- Discussion
- Latest Healthy Life Extension Headlines

METHUSELAH FOUNDATION UPDATE

It's in the weekly news at the end of this newsletter, but don't miss this update on fundraising and longevity research:

http://blog.methuselahfoundation.org/2008/01/methuselah_foundation_fundrais_1.html

"So, what's the bottom line? $1,860,000 received or pledged within the last 60 days! ... these additional funds will more than double the amount that we can spend on SENS research in 2008 relative to 2007. We plan to put this money to work by increasing the manpower on both our existing SENS projects (LysoSENS and MitoSENS), and by initiating at least two new projects."

Find out more about Strategies for Engineered Negligible Senescence (SENS) research at the Methuselah Foundation website:

http://www.mfoundation.org/sens

FREE ACCESS TO REJUVENATION RESEARCH

The full text of the December 2007 issue of Rejuvenation Research is presently freely available online. These promotions don't last too long, so jump in while you can. In addition to the scientific papers, you'll find the usual array of interesting articles aimed at the layperson:

https://www.fightaging.org/archives/001402.php
http://www.liebertonline.com/toc/rej/10/4

Articles include an interview with Paul Glenn - the force behind the Glenn Foundation for Medical Research and the Paul F. Glenn Laboratories for the Biological Mechanisms of Aging - and a pointed commentary on attitudes to longevity from William Bains:

"The question is not, 'Do you want to live forever?' The question is, 'Do you want to die tomorrow?' Replacing 'should we live forever' with 'do you want to die tomorrow?' strips away the sheer nonsense that is spouted about what 'might be,' and brings us back to specifics. Many people state firmly that they do not want to live forever. Many say they would not want to live beyond 100. Usually they are less than 60 years old when they say it (few 95-year-olds hold this view; very few 99-year-olds). But these people appear genuinely to feel that they do not want to live to be 100. So they do not want to live another 50 years. Do they want to die tomorrow? No. If I ask again tomorrow, will they want to die the day after? No."

THE CHALLENGES OF LONG-TERM CRYOSUSPENSION

The cryonics industry is moving more adroitly towards greater growth and professionalism these days, as illustrated by efforts at Alcor and a greater number of initiatives aimed at advancing the technology base, education, spin-off technologies and commercialization:

https://www.fightaging.org/archives/001398.php

"Cryonics, for those new to the party, is a form of low temperature storage of the body, vitrified rather than frozen to preserve the fine structure of your brain and all the information it contains - preserve your self, in other words, waiting for the likely technology of the 2040s or later that can repair and revive a cryopreserved individual. It is very plausible, very sensible and less supported than it should be. Just like serious research into rejuvenation technology, cryonics suffers from the mass acceptance of - and even impassioned advocacy for - aging and death we see in the world today.

"But back to the question: how to best ensure the continuation of an organization and its resources such that cryopreservation of vitrified customers continues solidly for half a century or longer? For added value, you'd want an organization that contributes to and helps to build the research communities developing revival technologies. You can be sure that a lot of thought has gone into this matter over the decades that cryonics providers have already existed."

You'll find links in that post to a fair amount of writing on the topic, as well as recent updates from Alcor on initiatives aimed at ensuring the continuation of service for as long as is necessary. How long will that be? Your guess is as good as mine, but molecular manufacturing technologies will probably be in full swing by the 2040s. For a taste of what that might mean, have a look back in the Fight Aging! archives:

https://www.fightaging.org/archives/001096.php

THE DESTRUCTION BROUGHT ON BY EXCESS FAT

Our understanding of the biological mechanisms linking visceral fat to age-related damage and death continues to expand:

https://www.fightaging.org/archives/001399.php

The very short summary: "All that excess fat hanging around over the years generates atherosclerosis, which then kills you." Read the post above for a more detailed understanding as to why that is the case.

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/

Categorizing the Molecular Damage of Aging (January 25 2008)
http://pmid.us/18215483
Aging is molecular damage: how much faster can we progress to repair technologies with a detailed map of that damage? "One of the most fundamental molecular aspects of aging is accumulating oxidative damage caused by reactive oxygen species (ROS) as proposed by the free radical theory of aging. These unwanted chemical side products of normal metabolism lead to the formation of altered, less active and potentially toxic species of DNA, RNA, proteins, lipids, and small molecules. Due to gradually accumulating small contributions of irreversible reactions during ageing, uncatalyzed chemical side reactions occur with increasing frequencies and repair functions decline. Eventually key biochemical pathways are impaired by increasingly less efficient cellular stress management. In this review, we describe the chemical nature of nonenzymatic age-related modifications of proteins and provide an overview of related analytical challenges and approaches, with a focus on mass spectrometry. We include the description of a strategy to rapidly exploit the wealth of mass spectrometric information [for] the characterisation of age-related oxidative amino acid modifications."

The Broad, Long Avenue of Progress Ahead (January 25 2008)
http://www.timesonline.co.uk/tol/comment/columnists/guest_contributors/article3254111.ece
This Times Online columnist gets it; wrong in the details of the science that will most likely liberate us from age-related degeneration, but right in the grand scope of what is possible: "Until 1828 it was believed that life, with its so-called 'vital forces', owed nothing to science, but in that year Friedrich Wohler synthesised urea in the test tube. Since then, chemistry's invasion of biology has been unstoppable. So it is not science fiction, it is inevitable, that within our children's lifetimes, molecular biologists will tweak the human genome. If we can re-create existing bacterial genomes, we will be able to create new improved human ones. The ills that flesh is heir to are many, but thanks to DNA chemistry they will be abolished. Diseases such as cystic fibrosis or muscular dystrophy will be eliminated as thoroughly as smallpox. And the greatest ill of all - ageing - will also be conquered. It was Sir Francis Bacon, the Father of the Scientific Method, who wrote in his Valerius Terminus of 1603 that the purpose of science was the 'discovery of all operations and possibilities of operations from immortality (if it were possible) to the meanest mechanical practice' - and immortality is possible."

More Vacularization By Stem Cell Transplant (January 24 2008)
http://www.eurekalert.org/pub_releases/2008-01/ef-asc012408.php
As a companion piece to the clinical trial noted yesterday, here's more stem cell research aimed at blood vessel repair and regrowth: "Multipotent adult progenitor stem cells extracted from bone marrow, and known as MAPCs, have proved to be effective in the regeneration of blood vessel tissue and also in muscle tissue when treating peripheric vascular disease. ... Acute peripheric vascular disease involves the obstruction of the blood circulation in a determined area of the organism, as a consequence of the occlusion of the artery supplying blood to it, with the consequent reduction in blood flow. ... The most important finding from the research was that adult MAPC stem cells are more effective when injected without pre-differentiation, not only because they contribute in increasing the quantity of arteries and veins generated in the new area, but also because they manage to enhance muscle regeneration [as] a consequence of secreting a series of substances. The research thus concluded that the MAPC progenitor cells implanted in mice achieved an indirect improvement of the muscle and a direct enhancement of the vessels."

What Is Aging? (January 24 2008)
http://pmid.us/18208348
As good a definition as any in this paper: "Aging at the molecular level is characterized by the progressive accumulation of molecular damage. The sources of damage act randomly through environmental and metabolically generated free radicals, through spontaneous errors in biochemical reactions, and through nutritional components. However, the occurrence of damage on a macromolecule may depend on its structure, localisation and interactions with other macromolecules. Damages in the maintenance and repair pathways comprising homeodynamic machinery lead to age-related failure of homeodynamics, increased molecular heterogeneity, altered cellular functioning, reduced stress tolerance, diseases and ultimate death." This means that any therapy capable of effectively intervening in aging must "incorporate means to minimize the occurrence and accumulation of molecular damage." At the high level, the most important debate in biogerontology today is over whether to work to slow the damage or repair the damage. I favor the latter course.

The State of Knowledge of Longevity Genes (January 23 2008)
http://pmid.us/18208581
An overview: "Ample evidence from model organisms has indicated that subtle variation in genes can dramatically influence lifespan. The key genes and molecular pathways that have been identified so far encode for metabolism, maintenance- and repair mechanisms that minimize age related accumulation of permanent damage. Here, we describe the evolutionary conserved genes that are involved in lifespan regulation of model organisms and humans, and explore the reasons of discrepancies that exist between the results found in the various species. In general, the accumulated data has revealed that when moving up the evolutionary ladder, together with an increase of genome complexity, the impact of candidate genes on lifespan becomes smaller. ... currently used methodologies may have only little power and validity to reveal genetic variation in the population. In conclusion, although the study of model organisms has revealed potential candidate genetic mechanisms determining aging and lifespan, to what extent they explain variation in human populations is still uncertain." Genetic and metabolic manipulation in humans - changing our biology - is not the way ahead for the near term. Rather, we need to learn how to repair the damage of aging in the biology we have today.

Stem Cells and Blood Vessel Regrowth (January 23 2008)
http://www.eurekalert.org/pub_releases/2008-01/nu-rts012108.php
EurekAlert! notes that stem cell therapies continue to show promise as a way to regrow damaged blood vessels: researchers have "launched the first U.S. trial in which a purified form of subjects' own adult stem cells was transplanted into their leg muscles with severely blocked arteries to try to grow new small blood vessels and restore circulation in their legs. ... Severely blocked arteries in the leg and sharply diminished blood flow can result in wounds that don't heal, the breakdown of tissue and gangrene. This painful condition is called critical limb ischemia (CLI) and results in the amputation of more than 100,000 limbs every year in the United States. ... An estimated 15 percent of the population will have this disease by the time they reach age 70. ... The stem cells themselves can assemble into blood vessels. They can also secrete growth factors that stimulate and recruit other stem cells to come into the tissue and help with the repair. It's an amazing biology we're trying to leverage in these folks. ... transplanting stem cells into the limbs have shown this approach to be effective in mice and rats. ... Based on that, we think it has a good chance of helping humans."

The Two Sides of Biogerontology (January 22 2008)
http://news.independent.co.uk/sci_tech/article3362350.ece
There's nothing like a good divide to get the press interested. Here's a view from the Independent of the two ends of biogerontology: "Valter Longo is one of the small but influential group of specialists in this area who believes that an 800-year life isn't just possible, it is inevitable ... We're very, very far from making a person live to 800 years of age. I don't think it's going to be very complicated to get to 120 and remain healthy, but at a certain point I think it will be possible to get people to live to 800. I don't think there is an upper limit to the life of any organism ... The attitude of most mainstream gerontologists towards the idea that people may one day live for many centuries - or even 1,000 years, as one scientific maverick has suggested - is best summed up by Robin Holliday ... Like many experts on the science of ageing, Holliday is deeply sceptical about the idea that the ageing process can somehow be circumvented, allowing people to extend their lives by decades or even centuries. ... The whole [anti-ageing] movement not only becomes science fiction; it is also breathtakingly arrogant, Holliday says. An immense hinterland of biomedicine suggests that death at a maximum age of about 125 is inevitable." In other words, sensible people who know how science and progress works versus the flat-earthers who don't. The article is actually somewhat wrong in that respect: the majority of the community these days is much closer to Longo than to Holliday in outlook.

Methuselah Foundation Funding and Research Update (January 22 2008)
http://blog.methuselahfoundation.org/2008/01/methuselah_foundation_fundrais_1.html
From the Methuselah Foundation blog: "We wanted to provide a view of this recent fundraising for all supporters of the Methuselah Foundation - and of our work on the Mprize for longevity science and Strategies for Engineered Negligible Senescence (SENS) research - so we've pulled together a list of the high points, and an overview of where these new resources will be put to use. ... all of this wind was in our collective sails when Foundation chair Aubrey de Grey and SENS program director Jeff Hall met with Peter Thiel for the latest of our periodic updates. Peter was so pleased and excited by this very strong, broad show of support for longevity research that he decided on the spot to donate the full remaining balance of his $1,000,000 matching pledge for 2007! We're still doing the calculations, but it looks like this will add more than $750,000 in new funding, cash in hand and ready to be used in the laboratory, for the Foundation. So, what's the bottom line? $1,860,000 received or pledged within the last 60 days! ... these additional funds will more than double the amount that we can spend on SENS research in 2008 relative to 2007. We plan to put this money to work by increasing the manpower on both our existing SENS projects (LysoSENS and MitoSENS), and by initiating at least two new projects."

The New Mainstream Scientific View of Longevity Research (January 21 2008)
http://pipeline.corante.com/archives/2008/01/21/breaking_the_contract_of_aging.php
Matters have certainly moved along in the past decade. The conservative view in gerontology is now that greater human longevity is desirable and can be engineered through metabolic manipulation - a great improvement over the previous state of affairs, but still a way to go yet towards the SENS model of repair and radical life extension. This In the Pipeline post typifies the mainstream view, I think, including a knee-jerk labeling of ongoing SENS longevity research as "fringe": "first, it's increasingly clear that there are deep connections between metabolism and lifespan. All sorts of genes related to food intake and insulin signaling affect how long model organisms live, and there's every reason to expect that the same is true of us. Second, the settings for our lifespans may not be optimal - or what we'd now consider optimal. ... there's no reason that we necessarily have to accept whatever tradeoffs were made during the development of our species. ... ever since our brains became large and complex enough for language and culture, and ever since we started growing our own food, we've been altering the evolutionary bargains that all other species have had to make - predator/prey relationships, availability of food, and so on. We may yet be able to draw a black line through another paragraph of the contract, and make it stick."

The Capital Market View of Changing Longevity (January 21 2008)
http://globalpensions.com/showPage.html?page=gp_display_feature&tempPageId=686565
I think this piece from Global Pensions is representative of the way the behemoths of the insurance and other capital markets are viewing the prospects for increasing longevity: "Could longevity experience a spike if there was a dramatic breakthrough in medical science, if someone found a cure for cancer for example? ... That would not change mortality statistics suddenly. It would take a long time to filter through. If some of the drugs being tested at the moment come on stream between now and 2020 then you would not see a significant impact until the middle of the century. Our model factors in the impact of significant medical advances and the key point for investors is that longevity is nevertheless a trend exposure rather than a spike, or event risk as is the case with mortality - and yet mortality bonds have nevertheless found a fairly broad marketplace." This sort of thinking - in any market - is why disruptive innovations are disruptive. The behemoths are right in that onerous regulatory burdens greatly slow advances in medicine, but success in Strategies for Engineered Negligible Senescence (SENS) or SENS-like work will be the disruption here. I'd say that betting vast sums against greatly increasing longevity in in the midst of a biotechnology revolution isn't such a good idea.

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