(From PhysOrg.com). Funding is increasing for the development of ambitious diagnostic nanomedicine, the first wave of more advanced biomedical ("wet") nanotechnology. "Georgia Institute of Technology and Emory University [awarded] $11.5 million to establish a new research program focused on creating advanced nanotechnologies to analyze plaque formation on the molecular level and detect plaque at its early stages." The tools proposed here would represent a modest but significant step towards medical nanorobots of the sort envisaged by Robert Freitas. Advanced nanotechnology is a tool for the second wave of healthy life extension medicine, picking up where regenerative medicine and effective cancer therapies leave off.

Link: http://www.physorg.com/news3933.html

Via Responsible Nanotechnology, here is an interesting illustration of the pace of progress:

The first image is from the game Pacman, released in 1980. At the time it was considered to be an innovative video game.

The second image is Half-Life 2, released just a few months ago. It too is considered to be an innovative video game.

These two games are separated by only 25 years, yet they look like they are from completely different planets. One is a flat, pixelated, handful-of-colors-on-a-mostly-black-screen game. The other is a photo-realistic real-time romp through an artifical world of incredible depth and detail. The two games cannot be compared. It would be like comparing a backhoe to a spoon.

An awareness of this rate of change - which could just as well be illustrated by examples pulled from the world of medicine - is why advocates for healthy life extension are pushing for funding now. Transformative technological change in two decades, while perfectly possible, can only be achieved in an environment of public support, expressed desire and high levels of funding. Substantial progress towards working anti-aging medicine is quite possible in a time frame of 25 years - just as substantial progress in cancer therapies has been made in the past 30 years - but only if we start from a position of widespread enthusiasm and a large funding base.

Unfortunately, we don't have either of these items yet, but we're working on it - join in and make a difference!

(From Small Times). The rapidly falling cost of DNA sequencing will lead to a future in which medicine is truly unique and personalized for each individual: "detailed blood analysis and a person's genetic sequencing [could] move medical diagnosis from the reactive to the predictive. ... doctors could use this approach to potentially detect life-threatening medical problems early enough to save people. ... If you can do early diagnosis, you can cure most cancers. We can't just do it right now. ... Each human organ has, through the blood, a unique molecular fingerprint that reports the status of that organ. Hence, if we can read these blood molecular fingerprints, we will have the capacity to assess health and diseases."

Link: http://www.smalltimes.com/document_display.cfm?document_id=9132

One vision of stem cell medicine is, as this Forbes writer puts it, "to make human beings more like salamanders. When chopped into bits, salamanders regenerate. Humans don't. By exploiting an elegant natural process -- the body's ability to heal itself with stem cells -- scientists are hoping to find therapies or cures for a long list of conditions including spinal cord paralysis, heart failure and Alzheimer's. 'Humans have a mechanism that sort of dampens down that ability. Infusions of stem cells are basically overcoming the damping-down mechanism.'" The path ahead is quite clear from a high level viewpoint, but a great deal of work remains to fill in the details and achieve goals. Fortunately, funding and public support exist - it's amazing what can be accomplished with those two things in hand.

Link: http://www.forbes.com/lifestyle/health/feeds/hscout/2005/04/29/hscout525412.html

The Boston Herald reports on the embryonic stem cell research and therapeutic cloning bill passed by the Massachusetts senate. "The bill, which encourages embryonic stem cell research in Massachusetts, was approved by a 34-2 vote, meaning the Senate could easily override an expected veto by Gov. Mitt Romney. The legislation approved Tuesday by the Senate is a compromise between two separate versions approved last month in the House and Senate. It would allow scientists to create cloned embryos and extract their stem cells for research." This is another sign that the tide has turned from harm caused by outright opposition to (hopefully less) harm caused by regulation and politics as usual. It makes me wonder how any medical goals are accomplished, let alone the vital ones.

Link: http://news.bostonherald.com/localPolitics/view.bg?articleid=80342

For those of you interested in perusing the recently released National Academies Guidelines for Human Embryonic Stem Cell Research, here is a link to the text online. (The summary itself is twelve pages, so that should keep you busy for a while). I gather that various folks were working behind the scenes with the intent of ensuring that the end result would be a document that could be adopted by the California Institute for Regenerative Medicine (CIRM) - no sense in duplicating work when reuse can speed things up. Unfortunately, it looks like the rules prohibit the very necessary and ethical practice of compensating human egg donors - and various bioethicists would like to see even more prohibition of compensation. This is, not to put too fine a point on it, nuts: another fine example of what the medical establishment thinks of free choice, individual rights, personal responsibility and a free market.

If the folks managing CIRM want to see more rapid progress - as rapid as a government-managed program can be, that is - then they will refrain from adopting that part of these guidelines.

In the not so distant future, biotechnology will come to look much like present day software development. This is somewhat inevitable, given the falling cost of computing power. While a great deal of the newest biotechnology is powered by advances in computational technology, ultimately everything bio will benefit. Most currently real world experimental techniques - rather than just a select few - will become cheaper to carry out in simulation. Why spend millions keeping racks of mice when you can spend hundreds of thousands on reliable, tested software to do the same job - software that will become cheaper by an order of magnitude with each passing decade. Before this transition is even mostly underway, we will see an unleashing of talent comparable to that in open source software development today. Just look at how far and fast software has come in the last ten years compared to the ten before that...

For my money, the most interesting part of this process is the enabling effects of cheap computing power - and the tools to take advantage of it - on people who are not professional researchers. To put it another way, the line between researcher and nonresearcher will become very blurred, just as the line between programmer and nonprogrammer is today. The present open source software development community contains diverse individuals, small teams, academic, non-academic, corporate and non-corporate groups producing solutions for specific problems that bother them or inspire them. In the future, equally diverse organizations will form and collaborate to produce solutions for health and longevity using open biotechnology yet to come.

The most important result of open information sharing and falling costs is the way in which it opens up the priesthood - be it of programmers or biotech researchers - and allows a much wider range of people to add their skills, time, desires and ideas to the mix. Just as open source software development has led to a melting pot of innovative designs, better software and a blurring of traditional lines, so too will the open biotech movement of the future.

Looking at the tremendous dynamism and energy of the current software development space, I think that this can only be a good thing.

As a BBC article notes, "Breast and lung cancer rates have doubled around the world over the last 30 years ... much of the growth was due to more people living longer - as cancer is a disease which usually affects older people." As more people live longer lives, age-related conditions become more common. Fortunately, cancer research is very well established and very well funded; more than a dozen potential new types of therapy are in the works and the US National Cancer Institute is predicting cancer to largely be brought under control by 2015. Which then just leaves the remaining hundreds or thousands of age-related degenerative conditions, known and unknown ... wouldn't it be far more efficient just to develop working anti-aging medicine instead?

Link: http://news.bbc.co.uk/1/hi/health/4490271.stm

A short note from the LEF News reminds us that dealing with telomeres and associated cellular biochemistry is a complex business. "Telomere shortening limits the regenerative capacity of cells during aging and chronic disease but at the same time inhibits tumor progression ... telomere shortening in [mice] in combination with chronic liver damage significantly reduced organismal survival even though telomere shortening strongly inhibited liver tumor formation. ... This study gives experimental evidence that the negative impact of telomere shortening on [regeneration and survival] can surpass the beneficial effects of telomere shortening on suppression of tumor growth in the setting of chronic organ damage." We have this balance of effects for one case in a vast range of possible cases - much more research remains to be done.

Link: http://www.lef.org/news/LefDailyNews.htm?NewsID=2133&Section=AGING

First generation regenerative therapies based on adult stem cells are getting traction, as illustrated by this report from Medical News Today on Arteriocyte, a spin-out company from the Center for Stem Cell and Regenerative Medicine: "The first installment of the combined $1.4 million grant is for the first phase of a 10 patient study to test the safety of using stem cells to repair ischemic heart tissue caused by an inadequate blood supply to the heart. ... patients with blocked or damaged heart vessels will have stem cells drawn from their own blood. These cells will then be enriched in the laboratory and reinjected into the patients at the site of their damaged heart tissue. Researchers expect this procedure to trigger the growth of new blood vessels to replace damaged ones."

Link: http://www.medicalnewstoday.com/medicalnews.php?newsid=23404

It's been fairly well established that exercise can delay or reduce the risk of suffering many age-related conditions - Alzheimer's disease included. Here, ScienceDaily reports on further investigations into the biochemistry underlying the protective effects of exercise. "Physical activity appears to inhibit Alzheimer's-like brain changes in mice, slowing the development of a key feature of the disease, according to a new study. The research demonstrated that long-term physical activity enhanced the learning ability of mice and decreased the level of plaque-forming beta-amyloid protein fragments - a hallmark characteristic of Alzheimer's disease (AD) - in their brains. ... [exercise] may bring about a change in the way that amyloid precursor protein is metabolized."

Link: http://www.sciencedaily.com/releases/2005/04/050426214147.htm

You'll recall the recent study on mortality and weight that I wasn't overly impressed with. I've seen one or two articles of late in which negative comments were made about calorie restriction in this context. In an e-mail to the Extropy Chat list, Brian Delaney of the Calorie Restriction Society notes the fallacies inherent in this sort of thing:

No conclusions about the benefits of a CR program can be drawn from studies showing a correlation between weight and mortality. People trying to draw such a conclusion are committing a serious logical error, one with potentially devastating health consequences for those who buy the error.

"CR leads to a reduction in weight." Yes.

"A reduction in weight is a sign of CR." No.

CR is not about being thin. Naturally obese mice (ob/ob) on severe CR are still chubby, but live much longer than naturally thin mice not on CR. Energy-restriction shifts resources away from growth and reproduction towards repair and maintenance. Doesn't matter what you weigh.

Indeed, the assumption (or false conclusion) that "accidental/unintentional CR" is more likely to be found among the underweight is not only wrong, it may even be backwards. People in the countries whre these mortality studies tend to be conducted who are naturally thin have LESS reason to restrict their food intake (and note: food restriction is not the same as Calorie restriction -- though that's a minor point), given societal pressures to be thin.

The way to determine whether or not CR reduces mortality is to look at people on CR and compare them to people not on CR. This is being done. Some initial results include those reported by Fontana [1].

It will take a long time before we can be certain that CR dramatically reduces mortality, but it seems extraordinarily like that it does so, and we can be certain that risks of diseases of aging (certainly, type 2 diabetes) is reduced significantly.

There are LOTS of sensible reasons not to be on CR. Believing that "it doesn't work" isn't one of them.

[1] Fontana L, Meyer TE, Klein S, Holloszy JO.
"Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans."
Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6659-63. Epub 2004 Apr 19.

Michael Cooper pointed me to the Statsman web site that tracks and displays contribution information for the Folding@Home project. I've been gently encouraging folks to join the Longevity Meme Folding@Home team for a while now, so this seems like a good occasion to remind you all:

Folding@Home is a distributed computing project run under the auspices of the smart guys at the Stanford University Chemistry Department. They rely on the contributions of millions of hours of spare computing time by people like you and I. This processing time is used to solve the hardest, latest and most pressing problems in protein biochemistry.

The understanding gained by the Folding@Home team speeds up the search for therapies and cures for a number of important degenerative conditions of aging. Currently, Alzheimer's is at the head of the list.

...

Join the Longevity Meme Folding@Home team! Competition is a good thing, inspiring us to do better. Our team number is 32461. Enter this in the "Team Number" box when installing Folding@Home. If you are using Windows, you can always update this number and other options by right-clicking on the Folding@Home icon in your system tray and choosing the "Configure..." option.

You can view the Longevity Meme team statistics over at Statsman. Don't let your computer sit idle while not in use - put those extra processing cycles to work advancing our understanding of human biochemistry and age-related conditions!

Another Edmonton Sun piece looks at progress towards healthy life extension, including opinions from scientists on both sides of the feasibility debate. "Could we elongate human lifespans past a century or two? Researchers who study aging say it's possible - some say it's inevitable. The challenge is keeping your body fit and your wits keen past your 200th birthday. ... I don't think there's a practical distinction between the diseases of aging and aging itself. If nothing went wrong with us as we age, where would the aging be? ... Which is precisely the thinking behind the so-called longevity movement, which seeks to slow or even stop the aging process by approaching it as a series of treatable disorders."

Link: http://www.canoe.ca/NewsStand/EdmontonSun/News/2005/04/26/1013186-sun.html

Research into induced hibernation in mammals may turn out to have relevance for healthy life extension - as well as "to reduce the body's need for oxygen and lengthen the window of time for treating patients with trauma, stroke, cardiac arrest or cancer. It might also be useful in surgery." The Seattle Times reports that $10 million in venture funding has been obtained by researchers who have induced a state of reversible metabolic hibernation in mice. "Scientists have been able to induce hibernation in yeast, worms and zebrafish but not previously in mammals. Now that Roth has demonstrated it with healthy mice, Ikaria's first task will be to show it can be done safely in larger animals."

Link: http://seattletimes.nwsource.com/html/businesstechnology/2002253036_ikaria26.html

Well, I crossed the line into Papal discussion a few days ago, so I may as well go the whole hog and point to comments over at Cyborg Democracy:

On life extension and anti-aging: "Disposing of death is in reality the most radical way of disposing of life."

Glee. I look forward to seeing the justifications underlying that bizarre remark - not that this position is really any different from that held by the previous Pope. Although it has to be said, I'd take these views with more than a grain of salt if their holders didn't tend to cling so tenaciously to life using the best that modern medicine and wealth can buy. The glorification of suffering and death that is so prominently displayed in the Western Christian tradition is, at root, rank hypocrisy. It's all fine and well when it's someone else's suffering and death - but you won't catch a Pope refusing to prolong his own life with advanced medicine.

Fortunately, progress towards better medicine, greater control over our bodies and regenerative cures for age-related conditions seems to be happening despite the destructive wishes of the Vatican and other like-minded people. It would go faster if they would just make their own choices for themselves and stop trying to force the dire consequences of their worldview down our throats.

EurekAlert reports on trial results for a first generation gene therapy for Alzheimer's: "UCSD physician-scientists took skin cells from eight patients diagnosed with early Alzheimer's disease. The tissue was modified in the lab to express nerve growth factor (NGF), a naturally occurring protein that prevents cell death and stimulates cell function ... the genetically modified tissue was implanted deep within the brains of the eight patients who had volunteered for the study." The results were better than any existing therapy, but only slowed degeneration. Better results are to be expected as therapies become more tailored to address the underlying biochemistry of the condition.

Link: http://www.eurekalert.org/pub_releases/2005-04/uoc--acd041805.php

The LEF News notes a study suggesting at least some of the characteristic biochemistry of calorie restriction (CR) can be obtained by restricting just proteins in the diet: "Previous studies have shown that [CR] decreases mitochondrial oxygen radical production and oxidative DNA damage in rat organs, which can be linked to the slowing of aging rate induced by this regime. These two characteristics are also typical of long-lived animals. However, it has never been investigated if those decreases are linked to the decrease in the intake of calories themselves or to decreases in specific dietary components." It remains to be seen whether the results of this study translate into actual healthy life extension in mice, as for CR.

Link: http://www.lef.org/news/LefDailyNews.htm?NewsID=2117&Section=AGING

LONGEVITY MEME NEWSLETTER
April 25 2005

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.

______________________________

CONTENTS

- Life Terms and Radical Life Extension
- That Weight and Mortality Study
- On Being Distracted By the Little Things
- Discussion
- Latest Healthy Life Extension Headlines

LIFE TERMS AND RADICAL LIFE EXTENSION

I found myself talking about Papal succession this past week, rather to my surprise. A recent essay by Rand Simberg used the succession as a starting point for questions about the fate of life terms in a world of greatly extended healthy life spans. For my part, I think it's clear enough that change brings change. As and when scientists attain funding enough to build the technologies of radical life extension, we will start to see shifts in society to match. I imagine that lifetime positions will be one of the first things to go, but read the article and make your own minds up:

http://www.fightaging.org/archives/000459.php

THAT WEIGHT AND MORTALITY STUDY

I've sure that many of you noticed the furor over a recent study of mortality risk at various weight levels; it seems to show that slightly overweight people have a lower mortality rate. The sound-bite versions of this study are probably being taken the wrong way: people like to hear what they like to hear - anything to suggest that it's not so bad to be overweight will get a fair amount of attention. Don't reach for the donuts yet, however, as it's good to be conservative in matters scientific. Bear in mind that there are still a great many studies to show that being even slightly overweight greatly increases your risk of suffering age-related illnesses:

http://www.fightaging.org/archives/000458.php

As I have pointed out a number of times, we simply can't take each new study as the last word on any complex topic in science - statistics and human health are certainly both complex topics. The process of scientific investigation, research and debate on any given subject produces an array of papers supporting each major position as the years go by. Only slowly does the preponderance of evidence lean one way or another, and certain answers must wait for a complete understanding of the underlying processes and factors involved.

ON BEING DISTRACTED BY THE LITTLE THINGS

It's very easy to lose focus and join the chorus of folks talking about commonplace health details and differences of a year here and a year there in life expectancy or healthy life span. It's good that these things are discussed and it's good to pay attention, but medical science will be able to do far better than just a few extra years - if the funding exists, if there is widespread support, if people embrace the idea of a cure for degenerative aging.

Why settle for tinkering an extra year out of the engine if you can upgrade to something that will last an extra twenty ... or a hundred ... or more? Just because you can tinker now but that upgrade is somewhere in the future is no excuse to lose sight of the end goal. How much time and money did you invest in researching and maintaining your health this year? Compare that to the time and money you invested in making sure that the future of healthy life extension and longevity medicine is going to be up to scratch - why the disparity?

Take a step forward; if you can keep a retirement fund growing, you can certainly help real anti-aging science to grow, gain acceptance and produce results:

http://www.mprize.org

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

The Near Future Of Medicine (April 24 2005)
http://www.canoe.ca/NewsStand/EdmontonSun/News/2005/04/24/pf-1010857.html
An article from the Edmonton Sun looks at some of what we can expect from the next ten years in medicine: stem cell based regeneration medicine and gene therapies. "It could be the magic bullet, the medical technology that puts surgery permanently in the shade - if we can just figure out how to make the damn things work. ... In the long run, we see science getting around the use of embryos as stem cell sources. Stem cell therapy could lend itself to all kinds of degenerative diseases, blood-borne diseases, cancer. ... The so-called Northern Trial is being conducted on human patients at six cardiac hospitals across the country, including the U of A and St. Michael's in Toronto. It's one of the more promising applications of gene therapy - the use of cloned DNA to urge the human body to heal itself."

A Long-Term Aging Study (April 24 2005)
http://www.nydailynews.com/boroughs/story/302834p-259266c.html
The New York Daily News examines the Albert Einstein College of Medicine's long-term aging study, soon to expand to a larger study group. "The work is yielding clues about the aging brain, Alzheimer's disease and other forms of dementia, and how people can keep their minds sharper longer by engaging in mentally challenging activities, such as playing bridge or the piano. ... It used to be thought that dementia was a part of the aging process, but it is not. ... Researchers have found that high blood pressure, high cholesterol and diabetes increase the risk of Alzheimer's, and that on average memory loss accelerates seven years before people are diagnosed with the disease." All the more reason to get working on a treatment for the underlying problem - the aging process.

Keeping Stem Cells Totipotent (April 23 2005)
http://www.rferl.org/featuresarticle/2005/4/61E9E32F-9251-43A5-B179-C1B52C1C166B.html
Radio Free Europe / Radio Liberty profiles the work of researcher Petr Dvorak in the Czech Republic: "Dvorak was excited as he explained his laboratory's latest discovery -- a possible mechanism to keep human [embryonic] stem cells in their original 'blank' [totipotent] state. The leading international scientific journal in the field, 'Stem Cells,' is about to publish a paper detailing the findings. ... Embryonic stem cells do a couple of things. One, they will differentiate into all sort of cell types, and that's what excites everyone, because we can turn them, hopefully, in the long run, into cells that can be used for therapeutic purposes. But the problem is they do that when they feel like it, and we need to be able to control that."

Adult Stem Cells And Cancer Risk (April 23 2005)
http://news.bbc.co.uk/1/hi/health/4465717.stm
A number of articles have seen print this week about the possible cancer risk from adult stem cells; a team has demonstrated the ability of lab-cultured adult stem cells to become cancerous after many months of cultivation. This has always been regarded as a low level potential risk, but as this BBC piece notes, "stem cell lines maintained and developed in stem cell banks over a long period of time are currently only used for research purposes. They are not transplanted into people." Still, this shows that much more research into cellular behavior would be a good thing. That understanding feeds into many different fields: regenerative medicine, cancer research and aging research amongst them.

More Neurodegenerative Trials (April 22 2005)
http://www.camradvocacy.org/fastaction/news.asp?id=1361
(Reprinted at CAMR). "A University of Wisconsin-Madison researcher said he would ask federal regulators Friday to approve the first clinical trial injecting special stem cells into the spinal cords of people with the degenerative nerve ailment called Lou Gehrig's disease." It is good to see more promising signs of progress towards therapies for neurodegenerative conditions; this and similar work forms a platform on which to build a greater understanding of age-related damage to the brain. Unlike other organs, we can't just replace the brain with fresh tissue in a worst case scenario for healthy life extension - so we had better get very good at understanding, repairing and preventing the myriad ways in which this complex machine fails with age.

A Look At Alzheimer's Research (April 22 2005)
http://www.lef.org/news/LefDailyNews.htm?NewsID=2107&Section=AGING
From the Life Extension Foundation News, a look at current and near term efforts in Alzheimer's research. "Today, the only treatments for Alzheimer's are drugs that slow the symptoms. And by the time typical symptoms like memory loss begin to appear, the disease has already caused extensive brain damage. To counter that, the University of Arizona and a handful of other research centers around the country are working on a new track to identify tests like brain scans or blood samples that could detect Alzheimer's long before symptoms even start. At the same time, a new Alzheimer's treatment that would arrest a major cause of symptoms is undergoing clinical trials ... Champions of the treatment are so confident in its potential, they're calling it a vaccine."

Better, Faster Bone Generation (April 21 2005)
http://www.engineer.ucla.edu/news/2005/bones.html
UCLA scientists have found a new biochemical trigger for bone formation that is a large improvement over the previous standard: "For the average person, this new development potentially means faster, more reliable bone healing with fewer side effects at a lower cost. In more severe cases, such as in children born with congenital anomalies, the new protein may offer an advanced solution to repair cleft palates, which involves bone deficiencies, and also aid in repairing other bone defects such as fractures, spinal fusion and implant integration." Developments in bone generation can also be expected to help those suffering from osteoporosis, a common age-related condition of bone loss.

More On Making Cancer Age (April 21 2005)
http://www.medicalnewstoday.com/medicalnews.php?newsid=23223
(From Medical News Today). You may recall that some groups are making progress in turning off the ability of cancer to resist cellular aging. UK scientists are making confident pronouncements: "Halting the production of telomerase is evolution's way of preventing cancerous growth. I am very confident that we are working along the right lines by targeting this molecule. ... The aim of the project is to develop a series of candidate drugs, which will then enter clinical trials after our four-year project period. Although it may be a number of years before treatments will be available to patients, we are very confident that we have found cancer's 'Achilles Heel', and that by the end of the project we will be in a position to exploit it."

A Good Idea, Slowly Spreading (April 20 2005)
http://www.timesonline.com/site/printerFriendly.cfm?brd=2305&dept_id=478663&newsid=14372260
An article on research funding for the study of falls and mobility in the elderly contains a good idea that I'd like to see more of: "Many people believe that unsteadiness is a natural part of aging. But Studenski said it was once thought senility was inevitable, but is now known to not be universal. The center will try to debunk such myths as it promotes independence among the elderly." Moving all age-related degeneration from the "natural, will happen" column into the "problem, we should do something about it" column is an important part of advocacy for healthy life extension. We should not have to accept the indignities of accumulated damage and loss of function - it may be natural, but so were smallpox, anthrax and commonplace chronic childhood illnesses.

Inside A Stem Cell Therapy Trial (April 20 2005)
http://www.signonsandiego.com/news/science/20050420-9999-lz1c20stem.html
SignOnSanDiego.com takes an inside look at a successful trial of a bone marrow stem cell therapy for heart disease. These first generation therapies use the patients own stem cells, and scientists do not yet have a complete understanding as to why they work. "It's not clear, for instance, which type of bone marrow stem cell is specializing into myocytes. Researchers aren't even certain that bone marrow cells actually cross lineages to become heart cells. Rather, the transplanted cells might secrete proteins that spur the division of existing heart stem cells – or perhaps recruit stem cells from elsewhere. Distinguishing one type of cell from another in any tissue is still terribly difficult for scientists, as is tracking where cells and their differentiating progeny wind up."

Promising Gene Therapy For Blindness (April 19 2005)
http://www.dailytelegraph.news.com.au/story.jsp?sectionid=1274&storyid=2990150
(From the Daily Telegraph). Australian scientists are moving towards trialing a gene therapy for some forms of blindness: "Researchers at the Perth-based Lyons Eye Institute have also successfully reversed blindness in mice using gene therapy and are now preparing to trial the procedure on humans. The process entails a gene being injected directly into the eyes. In the case of 14 dogs that were born blind, four weeks after the initial treatment they regained full sight. The technology [will be] focused on people who either inherited the condition or lost their sight through diabetes or ageing." This research group aims to commence human trials within two years.

Towards More Human Trials (April 19 2005)
http://www.wired.com/news/print/0,1294,67266,00.html
Wired takes a look at the the timeline for the next wave of human trials in stem cell based regenerative medicine: "Several scientists have used embryonic or fetal stem cells to help rodents with spinal cord injuries walk again. The researchers travel the country showing videos of rats dragging their hind legs, followed by clips of them miraculously hopping around following stem-cell injections. The question now, especially in the minds of the 250,000 people in the United States with spinal cord injuries, is: When will the research transfer into helping humans? The answer depends on who you ask. Some scientists believe it could happen as soon as the end of this year. Others say that's too soon, and data from larger animals such as dogs or monkeys is necessary before researching with humans."

Evaluating Longevity Genes (April 18 2005)
http://www.sciencedaily.com/releases/2005/04/050417213244.htm
(From ScienceDaily). Researchers have been hard at work building out a larger set of knowledge of genes and aging in the humble nematode worm: "Worms that lack fully functional daf-2 exhibit significantly extended lives, persisting approximately twice as long as their wild-type counterparts. Daf-2 was first reported as a critical aging-associated gene in 1993, but since that time, scientists have identified dozens of additional genes that are crucial for longevity ... In an effort to perform a comprehensive analysis of gerontology-related genes, the researchers compared gene-expression libraries obtained from daf-2 mutants to those obtained from controls at different ages." Metabolic control and stress response genes appear to be the most affected by daf-2.

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I stumbled across a nice quote from James Vaupel today in a filler piece from The Age:

The Max Planck Institute says medical innovations, a better diet and less risk of sudden death in war or accidents means that every second child born in the industrialised world now has an even chance of living to more than 100.

"But 125, 130 years is not unreasonable to expect soon," said James Vaupel, the institute's expert on ageing. "Really, the potential to live even beyond this time is there."

With more talk of healthy life extension in the media, public support for funding research into longevity therapies will increase. What separates us from much longer healthy lives is a gulf of acceptance, will and funding ... the technology is almost secondary given that the path ahead is so clear.

An article from the Edmonton Sun looks at some of what we can expect from the next ten years in medicine: stem cell based regeneration medicine and gene therapies. "It could be the magic bullet, the medical technology that puts surgery permanently in the shade - if we can just figure out how to make the damn things work. ... In the long run, we see science getting around the use of embryos as stem cell sources. Stem cell therapy could lend itself to all kinds of degenerative diseases, blood-borne diseases, cancer. ... The so-called Northern Trial is being conducted on human patients at six cardiac hospitals across the country, including the U of A and St. Michael's in Toronto. It's one of the more promising applications of gene therapy - the use of cloned DNA to urge the human body to heal itself."

Link: http://www.canoe.ca/NewsStand/EdmontonSun/News/2005/04/24/pf-1010857.html

The New York Daily News examines the Albert Einstein College of Medicine's long-term aging study, soon to expand to a larger study group. "The work is yielding clues about the aging brain, Alzheimer's disease and other forms of dementia, and how people can keep their minds sharper longer by engaging in mentally challenging activities, such as playing bridge or the piano. ... It used to be thought that dementia was a part of the aging process, but it is not. ... Researchers have found that high blood pressure, high cholesterol and diabetes increase the risk of Alzheimer's, and that on average memory loss accelerates seven years before people are diagnosed with the disease." All the more reason to get working on a treatment for the underlying problem - the aging process.

Link: http://www.nydailynews.com/boroughs/story/302834p-259266c.html

Radio Free Europe / Radio Liberty profiles the work of researcher Petr Dvorak in the Czech Republic: "Dvorak was excited as he explained his laboratory's latest discovery -- a possible mechanism to keep human [embryonic] stem cells in their original 'blank' [totipotent] state. The leading international scientific journal in the field, 'Stem Cells,' is about to publish a paper detailing the findings. ... Embryonic stem cells do a couple of things. One, they will differentiate into all sort of cell types, and that's what excites everyone, because we can turn them, hopefully, in the long run, into cells that can be used for therapeutic purposes. But the problem is they do that when they feel like it, and we need to be able to control that."

Link: http://www.rferl.org/featuresarticle/2005/4/61E9E32F-9251-43A5-B179-C1B52C1C166B.html

A number of articles have seen print this week about the possible cancer risk from adult stem cells; a team has demonstrated the ability of lab-cultured adult stem cells to become cancerous after many months of cultivation. This has always been regarded as a low level potential risk, but as this BBC piece notes, "stem cell lines maintained and developed in stem cell banks over a long period of time are currently only used for research purposes. They are not transplanted into people." Still, this shows that much more research into cellular behavior would be a good thing. That understanding feeds into many different fields: regenerative medicine, cancer research and aging research amongst them.

Link: http://news.bbc.co.uk/1/hi/health/4465717.stm

Some interesting points are raised in an article I noticed today:

The aging population increase in the US and throughout the developed world appears to correlate with a switch from acute infectious diseases to chronic diseases as the major cause of morbidity and mortality.

Some diseases like ulcers and certain types of cancer, once thought to be primarily related to lifestyle factors, are now known to be caused by microorganisms, and many more syndromes, including some psychiatric conditions, may have a connection to infection.

Scientists propose that much of the (entirely incidental) increase in average and maximum healthy life span over the past century stems from removing the damage done to our bodies by disease over a lifetime. Less disease means less damage - which means a better chance of a longer life according to the reliability theory of aging. This article proposes that medical science has, to date, only managed to deal with the easy half of the disease problem:

Up until the late 20th century, health professionals believed that chronic diseases such as peptic ulcers and cervical cancer were caused in part by lifestyle factors such as diet, stress and exposure to environmental toxins. In the last several decades, researchers have compiled strong evidence that most peptic ulcers are caused by an infection with the bacterium Helicobacter pylori and can be treated with antibiotics. An infection with human papillomavirus (HPV), the cause of genital warts, appears to be the cause of cervical and other cancers.

In addition to H. pylori and HPV, the report lists 30 other microorganisms for which there exists strong evidence of an associated chronic disease. The report also lists over 40 other chronic diseases, including heart disease, Alzheimer's and schizophrenia, which are suspected of having an infectious cause.

Proving causation is difficult. Scientists have traditionally applied a series of tests, known as Koch's postulates, to establish that a specific microorganism does indeed cause the associated disease. Because of the complex nature of chronic illnesses, oftentimes it is not practical or even possible to use Koch's postulates to prove the infectious nature of chronic illness. The report recommends that new criteria for evaluating the strength of association between microbes and chronic illnesses be developed.

The lack of progress to date in more important age-related conditions may be as much a function of the difficulty of identifying a cause as it is a function of these conditions only becoming more prevalent as more people live longer lives.

I point this out as a matter of interest - it is of course still that case that far more progress in healthy life extension can and should be made by directed research into extending the healthy human life span. We do need cures for chronic age-related conditions (infectious agents or not), but a great deal of funding is already invested in that research. Not so for the fight to cure aging, alas.

(Reprinted at CAMR). "A University of Wisconsin-Madison researcher said he would ask federal regulators Friday to approve the first clinical trial injecting special stem cells into the spinal cords of people with the degenerative nerve ailment called Lou Gehrig's disease." It is good to see more promising signs of progress towards therapies for neurodegenerative conditions; this and similar work forms a platform on which to build a greater understanding of age-related damage to the brain. Unlike other organs, we can't just replace the brain with fresh tissue in a worst case scenario for healthy life extension - so we had better get very good at understanding, repairing and preventing the myriad ways in which this complex machine fails with age.

Link: http://www.camradvocacy.org/fastaction/news.asp?id=1361

From the Life Extension Foundation News, a look at current and near term efforts in Alzheimer's research. "Today, the only treatments for Alzheimer's are drugs that slow the symptoms. And by the time typical symptoms like memory loss begin to appear, the disease has already caused extensive brain damage. To counter that, the University of Arizona and a handful of other research centers around the country are working on a new track to identify tests like brain scans or blood samples that could detect Alzheimer's long before symptoms even start. At the same time, a new Alzheimer's treatment that would arrest a major cause of symptoms is undergoing clinical trials ... Champions of the treatment are so confident in its potential, they're calling it a vaccine."

Link: http://www.lef.org/news/LefDailyNews.htm?NewsID=2107&Section=AGING

Much of the currently funded research into healthy life extension - such as work on calorie restriction biochemistry and mimetics - is focused on manipulating metabolism. This is much akin to fine tuning an engine to get a better mean time to failure; not fixing the underlying problem so much as somewhat reducing the rate at which it causes damage. With that in mind, the healthy life extension community is currently pondering what to make of news that a hibernation state can be induced in mice:

Mark Roth, a biochemist at the Fred Hutchinson Cancer Research Center, Seattle, and his colleagues tried exposing mice to air laced with relatively low concentrations of the gas: within minutes, the mice seemed to fall unconscious. Their core body temperature dropped by some 20°C, and their breathing slowed from about 120 breaths a minute to fewer than 10, the team reports in Science.

When re-exposed to clean air after six hours, the mice bounced back without any evident side-effects, says Roth. "This indicates that it's possible to decrease metabolic rate on demand," says Roth.

Aside from the obvious uses in surgery and a range of life threatening circumstances, what can be done with this discovery in the arena of extending healthy life spans? That's a good question, but it's worth noting that some folks feel that investigating the biochemistry of large hibernating mammals is very relevant to healthy life extension.

UCLA scientists have found a new biochemical trigger for bone formation that is a large improvement over the previous standard: "For the average person, this new development potentially means faster, more reliable bone healing with fewer side effects at a lower cost. In more severe cases, such as in children born with congenital anomalies, the new protein may offer an advanced solution to repair cleft palates, which involves bone deficiencies, and also aid in repairing other bone defects such as fractures, spinal fusion and implant integration." Developments in bone generation can also be expected to help those suffering from osteoporosis, a common age-related condition of bone loss.

Link: http://www.engineer.ucla.edu/news/2005/bones.html

(From Medical News Today). You may recall that some groups are making progress in turning off the ability of cancer to resist cellular aging. UK scientists are making confident pronouncements: "Halting the production of telomerase is evolution's way of preventing cancerous growth. I am very confident that we are working along the right lines by targeting this molecule. ... The aim of the project is to develop a series of candidate drugs, which will then enter clinical trials after our four-year project period. Although it may be a number of years before treatments will be available to patients, we are very confident that we have found cancer's 'Achilles Heel', and that by the end of the project we will be in a position to exploit it."

Link: http://www.medicalnewstoday.com/medicalnews.php?newsid=23223

Rand Simberg ties papal succession (a topic I have to admit I didn't see showing up here) and healthy life extension together in his latest article:

Despite his years, though, they may get a lot more continuity than they bargained for. This is, after all, the twenty-first century, in which technological breakthroughs in general, and medical breakthroughs in particular, are coming along at a breakneck and accelerating pace. Such advances, described in the recent books More Than Human by Ramez Naam, and Joel Garreau's Radical Evolution, may upend (among many other things) the stately applecart of traditional papal successions if (as seems increasingly likely) they result in extreme life extension and indefinitely-long healthy human life spans.

...

In a world of conventional life spans, we can always console ourselves with the thought that, if we're stuck with a dud pope, or a particularly nasty and competent dictator, or an overactivist judge, no one lasts forever.

...

If, as many think, this pope was selected to provide at least a temporary bulwark against modernity, how ironic that one of the features of modern life that he might be having to fight could also be one that could allow his own obstruction to it to be permanent

I think that it's clear that change means change - as and when scientists attain funding enough to build the technologies of radical life extension we will start to see shifts in society to match. I imagine that lifetime positions will be one of the first to go. Large organizations like to maintain the status quo, and the status quo is a certain amount of turnover.

As a side note, I've never found the immortal dictator to be a particularly convincing objection to healthy life extension. For a start, it's also an objection to all modern medicine and its life-prolonging effects. Secondly, how many dictators manage to maintain their position for life at the moment?

A study on the health risks of being overweight has been in the news of late, as it declares the effect on mortality rates of modest excess weight to be much lower than previously estimated. This sort of news is always received well for all the obvious (and poor) reasons - people like to be told that they aren't doing so badly after all.

Unfortunately, we simply can't take each new study as the last word on any complex topic in science; statistics and human health are certainly both complex topics. The process of scientific investigation, research and debate on any given subject produces an array of papers supporting each major position as the years go by. Only slowly does the preponderance of evidence lean one way or another, and certain answers must wait for a complete understanding of the underlying processes and factors involved.

I have opined before on the merits of being a conservative late adopter in matters relating to healthy and healthy life extension; the points are still valid. A wait and see attitude is a good thing in my book:

Science is a debate aimed at discovering the truth, supported by tested methodologies for determining, reviewing, interpreting and predicting facts. Important questions, especially those related to medicine and statistics, are not answered with a single study. Each study, and the resulting debate, can take years. Building - or changing - even a preliminary scientific consensus on any position is a process that spans decades.

People are hungry for definitive answers. Nobody likes an unanswered or partially answered question, but unanswered questions are the essence of science. All "answers" provided by science are theories, possibly wrong in as-yet undetermined ways, and subject to replacement when a better theory emerges.

So while looking at this latest study on one hand and a plate of donuts on the other, bear in mind that there are still a great many studies out there to demonstrate that even modest excess weight greatly increases the chance of suffering common age-related diseases. A last word from the article linked above:

Dr. JoAnn Manson, chief of preventive medicine at Brigham and Women's Hospital in Boston, said she is not convinced that the new estimate is right: "It's likely there has been a weakening of the mortality effect due to improved treatments for obesity. But I think this magnitude is surprising and requires corroboration."

Improved treatments or not, it's probably not a good idea to expect medical science to rescue you from the future costs - financial and otherwise - of failing to take care of your health now.

An article on research funding for the study of falls and mobility in the elderly contains a good idea that I'd like to see more of: "Many people believe that unsteadiness is a natural part of aging. But Studenski said it was once thought senility was inevitable, but is now known to not be universal. The center will try to debunk such myths as it promotes independence among the elderly." Moving all age-related degeneration from the "natural, will happen" column into the "problem, we should do something about it" column is an important part of advocacy for healthy life extension. We should not have to accept the indignities of accumulated damage and loss of function - it may be natural, but so were smallpox, anthrax and commonplace chronic childhood illnesses.

Link: http://www.timesonline.com/site/printerFriendly.cfm?brd=2305&dept_id=478663&newsid=14372260

SignOnSanDiego.com takes an inside look at a successful trial of a bone marrow stem cell therapy for heart disease. These first generation therapies use the patients own stem cells, and scientists do not yet have a complete understanding as to why they work. "It's not clear, for instance, which type of bone marrow stem cell is specializing into myocytes. Researchers aren't even certain that bone marrow cells actually cross lineages to become heart cells. Rather, the transplanted cells might secrete proteins that spur the division of existing heart stem cells – or perhaps recruit stem cells from elsewhere. Distinguishing one type of cell from another in any tissue is still terribly difficult for scientists, as is tracking where cells and their differentiating progeny wind up."

Link: http://www.signonsandiego.com/news/science/20050420-9999-lz1c20stem.html

There is nothing unusual, radical or strange about working towards extending the healthy human life span.

We are forced to rely on a valuable, complex machine - our bodies - in everything that we do. Like all machines, it tends to run down and eventually stop working; the process is unpleasant and we would prefer to make longer and better use of this machine. As for all machines, we can research better means of preventative maintenance and repair. If we can keep a vintage car in good condition for so long as we care to spend resources on it, we can certainly work towards the same capacity for the human body. Complexity is just a matter of degree - there is nothing mystical about cells and genes, no more so than for crankshafts and fan belts. The dividing line is between things we know how to do and things we don't yet know how to do.

Thus healthy life extension is simply common sense; the same common sense you apply to making the most of every other machine in your life. If you don't know how to do it, you learn.

(From the Daily Telegraph). Australian scientists are moving towards trialing a gene therapy for some forms of blindness: "Researchers at the Perth-based Lyons Eye Institute have also successfully reversed blindness in mice using gene therapy and are now preparing to trial the procedure on humans. The process entails a gene being injected directly into the eyes. In the case of 14 dogs that were born blind, four weeks after the initial treatment they regained full sight. The technology [will be] focused on people who either inherited the condition or lost their sight through diabetes or ageing." This research group aims to commence human trials within two years.

Link: http://www.dailytelegraph.news.com.au/story.jsp?sectionid=1274&storyid=2990150

Wired takes a look at the the timeline for the next wave of human trials in stem cell based regenerative medicine: "Several scientists have used embryonic or fetal stem cells to help rodents with spinal cord injuries walk again. The researchers travel the country showing videos of rats dragging their hind legs, followed by clips of them miraculously hopping around following stem-cell injections. The question now, especially in the minds of the 250,000 people in the United States with spinal cord injuries, is: When will the research transfer into helping humans? The answer depends on who you ask. Some scientists believe it could happen as soon as the end of this year. Others say that's too soon, and data from larger animals such as dogs or monkeys is necessary before researching with humans."

Link: http://www.wired.com/news/print/0,1294,67266,00.html

A little science from sci.life-extension to start the week off on the right foot:

Increasing evidence suggests that mitochondrial function declines during aging in various tissues and in a wide range of organisms. This correlates with an age-dependent large accumulation of specific point mutations in the mtDNA control region that was reported recently in human fibroblast and the skeletal muscle. However, it is rather rare to evaluate aging-related mtDNA mutations in other model animal systems. In this study, we analyzed mtDNA control regions of brain, skeletal muscle, heart, and other tissues from aged mice, in search of specific point mutations.

...

This may suggest that that humans have a better or tighter copy number control. Deletion mutations and clonal expansions occur in in human cells with relaxed copy number control but apparently not normally as in mice . If this is in fact true then this could presumably account for the longer lifespans and decreased ROS of humans in relation to mice.

The commentary is of course speculative (if well informed), but it is always good to see more work being done on mitochondria in the context of aging. Unlike many other areas of aging science, some groups are making headway on the required groundwork for repairing age-related damage in mitochondria.

(From ScienceDaily). Researchers have been hard at work building out a larger set of knowledge of genes and aging in the humble nematode worm: "Worms that lack fully functional daf-2 exhibit significantly extended lives, persisting approximately twice as long as their wild-type counterparts. Daf-2 was first reported as a critical aging-associated gene in 1993, but since that time, scientists have identified dozens of additional genes that are crucial for longevity ... In an effort to perform a comprehensive analysis of gerontology-related genes, the researchers compared gene-expression libraries obtained from daf-2 mutants to those obtained from controls at different ages." Metabolic control and stress response genes appear to be the most affected by daf-2.

Link: http://www.sciencedaily.com/releases/2005/04/050417213244.htm

FuturePundit has a good followup to recent discussions of the effects of great wealth on longevity. The bad news for billionaires is that "they can't buy much better medical care. They are super rich. They can buy any medical treatments available. But the same incurable diseases that kill most people in industrialized countries kill billionaires as well. The billionaires not only can't take it with them but they also can't use it to substantially delay their departure into the afterlife. There are limits to their buying power because of the deficiencies in our scientific knowledge about human biology. ... The lesson here for the billionaires is that if they want to extend their lives the best use of their own wealth is to fund more research and development aimed at developing better treatments."

Link: http://www.futurepundit.com/archives/002726.html

LONGEVITY MEME NEWSLETTER
April 18 2005

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

- Taking Responsibility for Your Future
- Discussion
- Latest Healthy Life Extension Headlines

TAKING RESPONSIBILITY FOR YOUR FUTURE

The sorts of discussions currently taking place regarding the future of socialized medical systems - such as Medicare in the US, or the NIH in the UK - should not inspire anyone with confidence. Take these two examples:

http://www.techcentralstation.com/041805D.html
http://www.longevitymeme.org/news/view_news_item.cfm?news_id=1624

"Krugman obviously thinks that the US currently pays too much for its health care and he might even be right. Yet as we know, the demand for health care is virtually unlimited, very few of us passing gently into the long dark night. There has to be some form of rationing, by price, by queue, by diktat, and if I'm right, and he's going to propose a system which is free at the point of treatment, by eliminating the price structure's effect in reducing demand, just how is he going to limit the system's costs?"

If advocates of healthy life extension and funding for working longevity medicine succeed in their efforts, radical change is in the air. If there's one thing that sprawling government entitlement programs do not handle well, it's change - even change for the better in the form of medical technologies that can greatly extend the healthy human life span. The culture of entitlement is an ugly thing to behold once it gets going:

http://www.fightaging.org/archives/000103.php

The bottom line is that you should not expect entitlement programs like Medicare, Social Security and so forth to continue to exist in their present form; it is simply impossible. Medicine has costs, and those costs must be paid in some way - but you shouldn't expect any organization or program to step up and pay the likely cost of the first generation of therapies to effectively intervene in the aging process:

http://www.fightaging.org/archives/000057.php

You do have time to plan for this uncertain future, however - it may take 10 years to establish a large funding base for directed, modern anti-aging research and a further 20 years of hard work to make meaningful progress on initiatives like Aubrey de Grey's SENS:

http://www.gen.cam.ac.uk/sens/

Thirty years is plenty of time to make a best effort to assure your health and longevity by assuring your financial security - by saving and planning ahead, in other words. Based on current trends and even a cursory look back at history, it would be foolish to count on other people's taxes as a source of payment for your longevity treatments (and unethical besides, but that's a whole other discussion). Just remember that when bad political policy runs headlong into economic reality, the unprepared are those who suffer the consequences.

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

Bidding With Public Funds (April 17 2005)
http://www.middletownpress.com/site/printerFriendly.cfm?brd=1645&dept_id=10856&newsid=14363174
A Middletown Press article accurately presents the way in which politicians view state funding of stem cell research - as a bidding war. "Seven states and counting are considering setting up or operating their own embryonic stem cell programs. The potential rewards in medical breakthroughs and economic development are so enormous that these legislatures are putting mountains of money on the line. However, Connecticut's proposed $20 million is a speed bump next to California’s $3 billion. ... New Jersey is proposing a $400 million stem cell program, and Wisconsin will launch a $750 million biotechnology program that includes stem cell research. 'Twenty million dollars is short-term. It's not enough to make Connecticut attractive. A lot more funding is needed.'"

Longevity And Future Health Costs (April 17 2005)
http://www.theaustralian.news.com.au/common/story_page/0,5744,12866417%255E23289,00.html
An article from the Australian is illustrative of the need for individual thought and responsibility regarding future healthcare and living costs that will accompany healthy life extension. Socialized medical systems - such as those in all Western countries these days - are going to struggle and collapse if the cost of working anti-aging procedures are significant at the point in time at which you require them. Worse, these systems inhibit investment in research and delay or block the deployment of new treatments through price controls and other economic malfeasance. Fortunately, you still have control over your personal savings - so plan responsibly for the future of radical life extension.

Aging And Calorie Requirements (April 16 2005)
http://www.medicalnewstoday.com/medicalnews.php?newsid=22903
An interesting snippet from Medical News Today when taken in the context of calorie restriction for healthy life extension: "Studies show adults' caloric needs drop about 10 percent or more from about age 30 to age 65 and older. Some of that decline may reflect a relative lack of physical activity in the elderly, and some may represent the body's basal metabolism slowing during aging. Part of the reason is that the body loses muscle - a prime consumer of energy - during the senior years. ... These body changes are neither irreversible nor permanent. Many seniors are actually able to add muscle mass and function into their 90s. You can defy what normal aging does to body composition by a careful balancing of food intake, exercise and vitamins."

Wound Healing Gene Identified (April 16 2005)
http://www.betterhumans.com/News/news.aspx?articleID=2005-04-15-2
Betterhumans reports that the master gene that controls wound healing has been identified: "the master gene, grainyhead, activates wound repair genes in cells surrounding injuries ... Such a conserved genetic mechanism for wound repair is considered an important find. Little is known about such things as how wound repair is halted when injuries are healed. Nor is it well understood how cancer cells evade this stop program." Things move very rapidly in a modern research environment once the underlying gene is identified. We should expect to hear details of the precise biomolecular mechanisms controlling wound repair in a year or so.

Stem Cell Legislation Overview (April 15 2005)
http://news.ft.com/cms/s/32375efc-ad17-11d9-ad92-00000e2511c8.html
For those who like to keep track of such things, the Financial Times is carrying an overview of current Federal stem cell politics in the US. "A bipartisan proposal to loosen restrictions on federal funding for stem-cell research has gained unexpected momentum in Congress ... As backing for the measure increased, Mr Castle won a surprising guarantee from Republican leaders for a vote on the issue by July 4." The normal cavaets apply: everything would go so much faster if politicians had left well alone at the start; politicians and their threats to ban research are the root cause of the current comparatively poor state of research. Legislatively imposed delays and regulatory costs translate to lost lives and suffering.

Searching For The Root Of Cancer (April 15 2005)
http://www.lef.org/news/LefDailyNews.htm?NewsID=2083&Section=DISEASE
The Life Extension Foundation News is reprinting a piece on the work of Thanos Halazonetis: "Cancer is more than 100 different diseases, and what this group has found is a commonality in early stages of development ... Since 1989, scientists have known that [the gene p53] plays a role in the way cells become cancerous ... Halazonetis, 45, argues that there is a way to kill a cell without p53. He said the DNA breaks occur only in cancerous or precancerous cells and therefore can be targeted and forced to die with or without p53's intervention." Early stage identification and prevention of cancer is a big deal - and a cure for cancer is absolutely essential to healthy life extension. A targetted therapy that only killed precancerous cells would be a real breakthrough, and scientists are nearing the point at which they can do this.

Regenerate 2005 (April 14 2005)
http://www.regenerate-online.com/
The strength of a field can be measured in conferences and new buildings - by this metric, regenerative medicine is doing well. The Regenerate 2005 conference in Atlanta this June is a good example of the current line of conferences focusing on the technologies of regenerative medicine: "Regenerate combines a premier scientific program with an industry-focused forum and trade show, bringing together basic scientists, clinicians, students, business development experts, entrepreneurs, and representatives of government funding agencies to advance the science of tissue engineering/ regenerative medicine." There are a number of interesting names and presentations noted in the agenda.

Crafting New Bone (April 14 2005)
http://www.dcexaminer.com/articles/2005/04/14/features/science/98science13bones.txt
An article from the Examiner looks at progress towards tissue engineered bone grafts based on the use of scaffolding materials, stem cells and knowledge of the chemical cues that prompt differentiation. "Under the microscope, the scaffold looks like a jungle gym made up of a bunch of little glass balls fused together. Each of the balls is composed of a polymer that harmlessly degrades in the body. To the polymer scaffold, he adds adult stem cells that have been isolated from a patient's fat tissue ... There they come under the influence of a [bone morphogenetic protein, or BMP] that has been also added to the scaffold ... One of the functions of BMPs is to transform adult stem cells in the bone marrow into bone-forming cells, or osteoblasts."

Alzheimer's Antibody Progress (April 13 2005)
http://www.newsday.com/news/printedition/health/ny-hs4215513apr13,0,2888436,print.story?coll=ny-health-print
Newsday.com reports on more progress towards the use of antibodies to attack Alzheimer's amyloid plaques: "The patients received infusions of immunoglobulin, a mix of antibodies derived from human blood donors. It was originally developed to treat children born with damaged immune systems and is now used for diseases including lupus and multiple sclerosis. ... The human antibodies in immunoglobulin destroy the sticky brain plaque called amyloid that is a hallmark of Alzheimer's. ... The benefit of the approach, called passive vaccine therapy, because it administers antibodies rather than require the body to manufacture the antibodies, is that it can be stopped at any sign of a problem."

Ronald Bailey On "Death Shortage" (April 13 2005)
http://www.reason.com/rb/rb041305.shtml
(From Reason Online). Ronald Bailey points out the flaws in "The Coming Death Shortage," a pro-death lament from the pen of Charles Mann. "Mann outlines an improbably dystopian vision of greedy geezers growing ever richer as their deserving children languish in poverty ... Mann dim-wittedly treats economics as a zero sum game. Evidently he thinks that there are a limited number of jobs available and the only way for a youngster to get one is for someone older to die. ... Slowing the Grim Reaper down will undoubtedly create some transition problems, but Mann has not identified any insuperable ones. The only shortage that he has demonstrated is the characteristic shortage of imagination that so many other pro-mortalists exhibit."

Sifting For Stem Cells (April 12 2005)
http://www.scienceblog.com/cms/node/7533
ScienceBlog notes an advance in the technology of identifying and isolating pluripotent adult stem cells. A truly efficient means of doing so would be a big boost to regenerative medicine based on the use of a patient's own stem cells to accelerate healing or replace damaged cells. "There are just 10,000 primitive cells in the average adult's bloodstream. Of those, only 500 might have the potential to replace embryonic stem cells. Stem cell research requires millions of these cells. ... Various properties of these primitive cells have been used to try and isolate the 5% or so with the highest stem cell potential, but no single technology has proved completely successful for human stem cells."

34th Annual AGE Meeting (April 12 2005)
http://www.americanaging.org/2005.html
The 34th annual meeting of the American Aging Association (AGE) - entitled "Aging: Mechanisms and Prevention" - will be held in California in June of this year. You may recognize some the names and research fields in the presentation list - calorie restriction and related research is featured extensively, and rightly so. There's much more than that, however, so take a look. "Among this year's topics, we count: genetic and cellular mechanisms of aging; role of IGF-1 signaling; caloric restriction in the human; genetics of human longevity; brain aging and novel therapies for neurodegenerative disease; use of genomics and proteomics in gerontological research.

Profiling Bob Klein (April 11 2005)
http://www.sfgate.com/cgi-bin/article.cgi?file=/c/a/2005/04/11/MNGKIC697P1.DTL
SFGate profiles Bob Klein, the wealthy patient advocate who is the driving force behind the $3 billion Proposition 71 and the new California Institute for Regenerative Medicine. "Robert Nicholas Klein II, 59, has no scientific or medical expertise, but managed to convince everyone who mattered, including Gov. Arnold Schwarzenegger, that he was the obvious choice to lead one of the world's most closely watched medical-research ventures, an enterprise that may serve as a model for states wanting to finance their own 'intellectual infrastructure' in the stem-cell field." There are many wealthy people in the world, but few who stand up and make real waves - we could do with more people like this backing directed research into longevity medicine.

The 25 Year Timeline (April 11 2005)
http://www.livescience.com/humanbiology/050411_aubrey_interview.html
Live Science is running an interview with our favorite biogerontologist, Aubrey de Grey; the focus is on his projected timeline for the development of effective therapies to halt or reverse aging. "Our human genomes will be modified to include the genetic material of microorganisms that live in the soil, enabling us to break down the junk proteins that our cells amass over time and which they can't digest on their own. People will have the option of looking and feeling the way they did at 20 for the rest of their lives, or opt for an older look if they get bored. Of course, everyone will be required to go in for age rejuvenation therapy once every decade or so, but that will be a small price to pay for near-immortality." You can read the details of Aubrey de Grey's proposals at his Strategies for Engineered Negligible Senescence website.

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A Middletown Press article accurately presents the way in which politicians view state funding of stem cell research - as a bidding war. "Seven states and counting are considering setting up or operating their own embryonic stem cell programs. The potential rewards in medical breakthroughs and economic development are so enormous that these legislatures are putting mountains of money on the line. However, Connecticut's proposed $20 million is a speed bump next to California's $3 billion. ... New Jersey is proposing a $400 million stem cell program, and Wisconsin will launch a $750 million biotechnology program that includes stem cell research. 'Twenty million dollars is short-term. It's not enough to make Connecticut attractive. A lot more funding is needed.'"

Link: http://www.middletownpress.com/site/printerFriendly.cfm?brd=1645&dept_id=10856&newsid=14363174

An article from the Australian is illustrative of the need for individual thought and responsibility regarding future healthcare and living costs that will accompany healthy life extension. Socialized medical systems - such as those in all Western countries these days - are going to struggle and collapse if the cost of working anti-aging procedures are significant at the point in time at which you require them. Worse, these systems inhibit investment in research and delay or block the deployment of new treatments through price controls and other economic malfeasance. Fortunately, you still have control over your personal savings - so plan responsibly for the future of radical life extension.

Link: http://www.theaustralian.news.com.au/common/story_page/0,5744,12866417%255E23289,00.html

I noticed another op-ed column on radical life extension today that, despite a promising start, manages to nicely bracket the common (mistaken) errors and objections regarding longer, healthier lives.

The down side? You get twice as long with that sore hip and arthritis. You must spend more time dealing with the inability to sleep through the night without getting up two or three times to visit the bathroom. You have to listen to several more generations talk about how you screwed up the world. You have to see all those "Murder, She Wrote" episodes over and over and over.

And worst of all, for many people, you have to spend 147 years working for The Man.

That was what I figured would be the biggest hurdle for most people - having to work day after day after day for nearly 15 decades. To work at the factory for 40 years and be just a quarter of the way into your career.

But nearly everyone would do it. What's your take? E-mail me with your feelings - ... bstanhope@dailyrepublic.net

I'd suggest doing your part for healthy life extension advocacy and writing to this fellow to point out the ways in which he gets it wrong - the Tithonus Error for the hips and arthritis; economic misunderstandings relating to savings and retirement; on insinuations of boredom. Wonderful rebuttals for all these points have existed for decades - we need to do a better job of spreading the word.

An interesting snippet from Medical News Today when taken in the context of calorie restriction for healthy life extension: "Studies show adults' caloric needs drop about 10 percent or more from about age 30 to age 65 and older. Some of that decline may reflect a relative lack of physical activity in the elderly, and some may represent the body's basal metabolism slowing during aging. Part of the reason is that the body loses muscle - a prime consumer of energy - during the senior years. ... These body changes are neither irreversible nor permanent. Many seniors are actually able to add muscle mass and function into their 90s. You can defy what normal aging does to body composition by a careful balancing of food intake, exercise and vitamins."

Link: http://www.medicalnewstoday.com/medicalnews.php?newsid=22903

Betterhumans reports that the master gene that controls wound healing has been identified: "the master gene, grainyhead, activates wound repair genes in cells surrounding injuries ... Such a conserved genetic mechanism for wound repair is considered an important find. Little is known about such things as how wound repair is halted when injuries are healed. Nor is it well understood how cancer cells evade this stop program." Things move very rapidly in a modern research environment once the underlying gene is identified. We should expect to hear details of the precise biomolecular mechanisms controlling wound repair in a year or so.

Link: http://www.betterhumans.com/News/news.aspx?articleID=2005-04-15-2

I know, I know, I keep giving you folks links to the Mprize multimedia page, but I did say that I would point out the video of Aubrey de Grey's appearance at BIOMEDEX 2005 when it became available. The direct links to the video are:

• RealPlayer Format
• MPEG
• MP3 Audio Only

For those who like to keep track of such things, the Financial Times is carrying an overview of current Federal stem cell politics in the US. "A bipartisan proposal to loosen restrictions on federal funding for stem-cell research has gained unexpected momentum in Congress ... As backing for the measure increased, Mr Castle won a surprising guarantee from Republican leaders for a vote on the issue by July 4." The normal cavaets apply: everything would go so much faster if politicians had left well alone at the start; politicians and their threats to ban research are the root cause of the current comparatively poor state of research. Legislatively imposed delays and regulatory costs translate to lost lives and suffering.

Link: http://news.ft.com/cms/s/32375efc-ad17-11d9-ad92-00000e2511c8.html

The Life Extension Foundation News is reprinting a piece on the work of Thanos Halazonetis: "Cancer is more than 100 different diseases, and what this group has found is a commonality in early stages of development ... Since 1989, scientists have known that [the gene p53] plays a role in the way cells become cancerous ... Halazonetis, 45, argues that there is a way to kill a cell without p53. He said the DNA breaks occur only in cancerous or precancerous cells and therefore can be targeted and forced to die with or without p53's intervention." Early stage identification and prevention of cancer is a big deal - and a cure for cancer is absolutely essential to healthy life extension. A targetted therapy that only killed precancerous cells would be a real breakthrough, and scientists are nearing the point at which they can do this.

Link: http://www.lef.org/news/LefDailyNews.htm?NewsID=2083&Section=DISEASE

President of the Gerontological Society of America, that is. You can find his campaign statement in their latest (PDF-format) newsletter:

In recent years, the biology of aging has become sexy. By that I mean that scientific efforts to understand, and purposely alter, the rate of aging - in animals now, but ultimately in humans - receives an inordinate amount of public attention. Those of us in the field note that it has now become easier to publish our papers in prestigious scientific journals. Our phones ring regularly with inquiries from journalists in both the print and electronic media asking for our interpretations and opinions about new scientific research to be sure, but also about the social, political, and ethical implications of our work.

The dirty truth of it is, of course, that as much as our opinions might be useful in interpreting new biological breakthroughs, most of us have given scant thought to the social, political, or ethical implications of our work. For all of the time we spend at our laboratory bench, we spend little time thinking about the day-to-day life, the personal pleasures, or social roles of the elderly ... which illustrates why the GSA is so vitally important. It is the only organization that routinely brings together people that should be talking to one another across discipline boundaries - caregivers, political scientists, biologists, educators, historians, and philosophers - and forces them to talk to one another. In doing so, it gives form and breadth and context to the work of all of us and makes us consider issues that we might easily avoid by locking ourselves solely in the company of our fellow specialists. I remember the first GSA meeting I attended featured a symposium, organized as I recall by Roy Walford, on the topic of whether it was ethically justifiable to medically retard aging. I was surprised to discover that not everyone considered (as the biologists did) that retarding aging was an unalloyed good thing. Moreover, the reservations expressed were meticulously thought out, clearly and forcefully expressed, and as I later discovered, quite representative of wider public opinion. My horizons were broadened in a way that no number of meetings with other biologists was likely to do.

Steven Austad is a good deal less conservative than many in the GSA when it comes to applying the lessons of aging research to extend the healthy human life span - having a more forward-looking and well known society president would be a positive step forward for the field.

The strength of a field can be measured in conferences and new buildings - by this metric, regenerative medicine is doing well. The Regenerate 2005 conference in Atlanta this June is a good example of the current line of conferences focusing on the technologies of regenerative medicine: "Regenerate combines a premier scientific program with an industry-focused forum and trade show, bringing together basic scientists, clinicians, students, business development experts, entrepreneurs, and representatives of government funding agencies to advance the science of tissue engineering/ regenerative medicine." There are a number of interesting names and presentations noted in the agenda.

Link: http://www.regenerate-online.com/

An article from the Examiner looks at progress towards tissue engineered bone grafts based on the use of scaffolding materials, stem cells and knowledge of the chemical cues that prompt differentiation. "Under the microscope, the scaffold looks like a jungle gym made up of a bunch of little glass balls fused together. Each of the balls is composed of a polymer that harmlessly degrades in the body. To the polymer scaffold, he adds adult stem cells that have been isolated from a patient's fat tissue ... There they come under the influence of a [bone morphogenetic protein, or BMP] that has been also added to the scaffold ... One of the functions of BMPs is to transform adult stem cells in the bone marrow into bone-forming cells, or osteoblasts."

Link: http://www.dcexaminer.com/articles/2005/04/14/features/science/98science13bones.txt

The full text of the recent New Scientist subscriber-only article "Welcome to the Immortals' Club" is available over at the Transhumantech Yahoo! Group. It's something of an outsider's view into the healthy life extension community and the debate within gerontology - and hence riddled with minor errors and misconceptions - but still worth reading.

De Grey knows he is outside the mainstream but insists he is on the right track. "Most of my colleagues in gerontology do appreciate that ageing in general is not a good idea, but they're completely convinced that nothing can be done about it in the near term," he says. "They're wrong. If I make it to 110, I reckon I'll have at least a 50:50 chance of making it to 1000 and quite possibly much more."

A pity that since it's a subscriber only article, comparatively few people will actually read it.

The divide between people who instinctively find healthy life extension and longer lives an obvious, wonderful goal and those who do not is an odd one. Speaking as someone who would like to live healthily for a long, long time, I often find pro-aging, pro-death folks downright incomprehensible.

It's always nice to see other people out there in the world who feel the same way:

The promise of extended life spans has never been more truer than today, and it will be even more true tomorrow. The technology is advancing with our understanding of the molecular machinery of the body. Will we have it beat in 25 years? I personally think that might be a bit optimistic, but those of us in my age bracket might be able to expect another twenty or thirty years above the norm, and that might stretch us long enough to see a major breakthrough someday.

Would you be bored by a three hundred year life lived at the biological age of 25? I've never really understood the downside of life extension, or the virtues of death in the face of potential rejuvenation. There will always be a segment of naturalists who will be content with their three score and ten, but it seems to be such a waste. By the time we have things figured out, it is too late to make meaningful change.

...

Either way, I wouldn't understand anyone who would refuse such potential.

Newsday.com reports on more progress towards the use of antibodies to attack Alzheimer's amyloid plaques: "The patients received infusions of immunoglobulin, a mix of antibodies derived from human blood donors. It was originally developed to treat children born with damaged immune systems and is now used for diseases including lupus and multiple sclerosis. ... The human antibodies in immunoglobulin destroy the sticky brain plaque called amyloid that is a hallmark of Alzheimer's. ... The benefit of the approach, called passive vaccine therapy, because it administers antibodies rather than require the body to manufacture the antibodies, is that it can be stopped at any sign of a problem."

Link: http://www.newsday.com/news/printedition/health/ny-hs4215513apr13,0,2888436,print.story?coll=ny-health-print

(From Reason Online). Ronald Bailey points out the flaws in "The Coming Death Shortage," a pro-death lament from the pen of Charles Mann. "Mann outlines an improbably dystopian vision of greedy geezers growing ever richer as their deserving children languish in poverty ... Mann dim-wittedly treats economics as a zero sum game. Evidently he thinks that there are a limited number of jobs available and the only way for a youngster to get one is for someone older to die. ... Slowing the Grim Reaper down will undoubtedly create some transition problems, but Mann has not identified any insuperable ones. The only shortage that he has demonstrated is the characteristic shortage of imagination that so many other pro-mortalists exhibit."

Link: http://www.reason.com/rb/rb041305.shtml

ScienceBlog notes an advance in the technology of identifying and isolating pluripotent adult stem cells. A truly efficient means of doing so would be a big boost to regenerative medicine based on the use of a patient's own stem cells to accelerate healing or replace damaged cells. "There are just 10,000 primitive cells in the average adult's bloodstream. Of those, only 500 might have the potential to replace embryonic stem cells. Stem cell research requires millions of these cells. ... Various properties of these primitive cells have been used to try and isolate the 5% or so with the highest stem cell potential, but no single technology has proved completely successful for human stem cells."

Link: http://www.scienceblog.com/cms/node/7533

The last third of a Pharmaceutical Business Review article caught my eye; it links the technologies of regenerative medicine with Aubrey de Grey's Strategies for Engineered Negligible Senescence proposals.

One of the more forward looking applications of human cloning research could be a 'cure' for aging, or at least the reduction of its effects and an increase in human longevity. Aubrey de Grey, a leading gerontologist, is a proponent of regenerative medicine, the emerging industry focused on the treatment strategy of replacing malfunctioning cells with fully functioning ones. He suggests a number of ways in which the 'disease' of aging can be stopped, or at least slowed down. One of his theories states that we could prevent age-related cancers by replacing our own stem cells with genetically engineered stem cells in which the genes that encode telomere-elongation are deleted.

These ideas could imply the use of genetic engineering alongside human cloning techniques to develop specific, disease free tissues that could be replaced as necessary. The prospect of human life expectancy extending well into an individual's second century, and maybe beyond, throws up some bizarre questions. A crucial consideration here is not just extending the period at the end of life or drawing out old age, but lengthening people's productive and active lives. Would longer lives mean lower birth rates? Or could we continue to extend our reproductive capacity as well? Furthermore, who would pay for the groundbreaking technology enabling them to live longer? The cost could be prohibitive to all but the wealthy few, meaning the 'haves' can live forever, but where does that leave everyone else?

Interesting - and promising - to now see this sort of discussion cropping up as the logical end to an article on therapeutic cloning, stem cells and regenerative medicine, regardless of the technical merits or accuracy of the piece. The slew of objections to healthy life extension have been addressed here before, needless to say.

(Feel free to critique in the comments, however).

The 34th annual meeting of the American Aging Association (AGE) - entitled "Aging: Mechanisms and Prevention" - will be held in California in June of this year. You may recognize some the names and research fields in the presentation list - calorie restriction and related research is featured extensively, and rightly so. There's much more than that, however, so take a look. "Among this year's topics, we count: genetic and cellular mechanisms of aging; role of IGF-1 signaling; caloric restriction in the human; genetics of human longevity; brain aging and novel therapies for neurodegenerative disease; use of genomics and proteomics in gerontological research.

Link: http://www.americanaging.org/2005.html

Leonid Gavrilov recently pointed the GRG list to an interesting discussion on the evolutionary theory of aging - complete with thoughtful comments from the likes of Richard Miller, Steven Austad and Andrzej Bartke.

I cannot imagine any theoretical construct more central to biogerontology than the evolutionary biological theory of aging (SN Austad, Why We Age, Wiley, NY, 1997). The theory applies to age-structured populations and to ecologies that dominated the early history of particular animal species. These early nature-nurture interactions shaped the genomes so that their life histories maximized reproductive fitness. In ecologies with high hazard functions, the more optimal life history would be one that involved rapid development, large numbers of progeny beginning shortly after the attainment of sexual maturity, and relatively short life spans. For the case of low hazard environments, a different life history strategy, one involving slower rates of development, longer periods of fecundity and longer life spans, might prove to lead to greater reproductive fitness. Tom Kirkwood's formulation invokes trade offs between the need for energetic resources for reproduction versus the need for energetic resources to maintain the soma (Kirkwood and Holliday, Proc R Soc Lond Biol Sci 205:531, 1979).

It's well worth a read for those of you who are interested in aging research.

SFGate profiles Bob Klein, the wealthy patient advocate who is the driving force behind the $3 billion Proposition 71 and the new California Institute for Regenerative Medicine. "Robert Nicholas Klein II, 59, has no scientific or medical expertise, but managed to convince everyone who mattered, including Gov. Arnold Schwarzenegger, that he was the obvious choice to lead one of the world's most closely watched medical-research ventures, an enterprise that may serve as a model for states wanting to finance their own 'intellectual infrastructure' in the stem-cell field." There are many wealthy people in the world, but few who stand up and make real waves - we could do with more people like this backing directed research into longevity medicine.

Link: http://www.sfgate.com/cgi-bin/article.cgi?file=/c/a/2005/04/11/MNGKIC697P1.DTL

Live Science is running an interview with our favorite biogerontologist, Aubrey de Grey; the focus is on his projected timeline for the development of effective therapies to halt or reverse aging. "Our human genomes will be modified to include the genetic material of microorganisms that live in the soil, enabling us to break down the junk proteins that our cells amass over time and which they can't digest on their own. People will have the option of looking and feeling the way they did at 20 for the rest of their lives, or opt for an older look if they get bored. Of course, everyone will be required to go in for age rejuvenation therapy once every decade or so, but that will be a small price to pay for near-immortality." You can read the details of Aubrey de Grey's proposals at his Strategies for Engineered Negligible Senescence website.

Link: http://www.livescience.com/humanbiology/050411_aubrey_interview.html

LONGEVITY MEME NEWSLETTER
April 11 2005

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

- A Smorgasbord of Mprize Multimedia
- What is Conservatism in Gerontology?
- On Wealth and Longevity
- Discussion
- Latest Healthy Life Extension Headlines

A SMORGASBORD OF MPRIZE MULTIMEDIA

The Methuselah Foundation volunteers have been amassing audio and video for a while now: media coverage of the Mprize for anti-aging research; interviews with Aubrey de Grey; presentations given at events like Pop!Tech. Over the past week, this has all gone online in one convenient place:

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

So stroll over and see what an Aubrey de Grey presentation really looks and sounds like; listen to what he has to say about the future of healthy life extension and funding for anti-aging research. If you like what you hear, give some thought to making a donation to the Mprize fund - your dollars will go towards making longevity medicine a reality.

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

WHAT IS CONSERVATISM IN GERONTOLOGY?

The largest institutional problem facing forward-looking scientists today is conservatism in the gerontological establishment. Conservatism in this case is an unwillingness to discuss any serious attempt to develop working healthy life extension medicine based on our current level of knowledge about aging. Conservative gerontologists uniformly call for more funding for aging research in order to better understand the biomolecular and genetic mechanisms of the aging process - a good thing in and of itself, but by no means sufficient.

http://www.fightaging.org/archives/000448.php

Imagine a world in which all that cancer researchers did was try to better understand cancer - a world in which the mainstream cancer research community refused to discuss any sort of progress towards actual therapies. Seems unthinkable doesn't it? We certainly didn't have a good understanding of cancer back in the 1970s compared to now, but that didn't stop people developing ever better, working, practical therapies. Yet in the cloistered world of gerontology, it is heresy to discuss the application of aging research to extend the healthy human life span; there is no funding for such efforts.

When we stand the progress and comparative stages of aging research and cancer research side by side, the absence of mainstream funding for applied research into therapies for aging is glaring. We know enough about aging and what it does (more than we did about the mechanisms of cancer in 1970) to get going - we have proposals like Aubrey de Grey's Strategies for Engineered Negligible Senescence awaiting serious discussion and criticism by other gerontologists.

http://www.gen.cam.ac.uk/sens/

What is needed here is a hard shove to dislodge this unhealthy conservative mindset in gerontology - one delivered by the raised voices of those who want to see working anti-aging therapies in their lifetimes.

http://www.longevitymeme.org/articles/viewarticle.cfm?page=1&article_id=16

ON WEALTH AND LONGEVITY

How many extra years of healthy life does wealth bring you? Not as many as you might think:

http://www.fightaging.org/archives/000443.php

"Simply having great wealth is not going to work wonders for your life span. You'll get a few extra years at most if all you are doing is enjoying the peripheral benefits. One of the hallmarks of this modern world is that the gap in consumer benefits enjoyed by the wealthy and the poor is not as large as you might think, nor as large as it once was. All the advances that would amaze a time traveler from the 1300s are largely available to the first world poor of our time.

There is one thing that wealth does bring, however, and that is the ability to effect change. Wealth is a big lever that can be used to shape the future - it would only take a small fraction of the holdings of the wealthiest 400 people in the world to set serious anti-aging research underway, for example. In other words, the best way to turn wealth into extra healthy years is to fund advances into working anti-aging and longevity medicine rather than simply enjoy the best medicine currently available. One of the goals of healthy life extension advocacy is to make that point clear to the wealthy of the world."

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

More On Centenarian Studies (April 10 2005)
http://www.capecodonline.com/cctimes/secretto10.htm
The Cape Cod Times reports on centenarian studies and the genetics of natural longevity - something that scientists would like to understand and use as the basis for therapies. "Currently in the United States, about one person in 10,000 lives to be 100 ... Perls divides centenarians into three categories: 'delayers,' who have no age-related illnesses until their 80s; 'escapers,' who have no illnesses at 100; and 'survivors,' who had age-related illnesses prior to turning 80. About 15 percent of centenarians are 'escapers' and the remainder are almost evenly divided into 'delayers' and 'survivors.' ... About 90 percent of the centenarians were functionally independent at the average age of 92."

No Missouri Research Ban? (April 10 2005)
http://www.boston.com/news/nation/articles/2005/04/10/in_missouri_gop_is_riven_over_embryonic_stem_cell_research?pg=full
Boston.com reports on stem cell politics in Missouri: "Last week, the Missouri Senate shelved a bill that would have banned somatic cell nuclear transfer, or so-called therapeutic cloning. ... State senators debated the measure for six hours without resolution last week. The bill's sponsor, Matt Bartle of suburban Kansas City, resisted calls to compromise or, as some Republicans would have preferred, to drop the proposal entirely. ... Dr. William Nieves, a self-described 'born-again Christian' who heads the Stowers Institute for Medical Research, has told legislators that the institute, which is endowed with more than $2 billion, will forgo an expansion and seek out a location 'more favorable to stem cell research' should the anti-cloning measure pass."

Nanomedicine At EuroNanoForum (April 09 2005)
http://nanodot.org/article.pl?sid=05/04/07/2030204
Nanodot notes that advanced nanomedicine of the sort advocated by Robert Freitas will be on the agenda at the EuroNanoForum 2005 conference later this year. Keeping the focus on medium to long term advances in the nanotechnology field has proven to be something of a battle over the past year - advocates and development plans for molecular manufacturing and nanomedical robotics were in danger of being shut out by an industry focused on short term goals such as nanoscale manufacturing and diagnostic tools. It is these long term goals for medical nanotechnology that have the most likelihood of producing large gains in the healthy human life span - so they should be nurtured and encouraged.

Alzheimer's And Mitochondria (April 09 2005)
http://www.medicalnewstoday.com/medicalnews.php?newsid=22500
An article from Medical News Today explains our current understanding of links between mitochondrial degeneration and Alzheimer's disease: "Proteins involved in brain cell communications, called synaptic proteins, decrease in the brains of Alzheimer's patients when compared to healthy brains from people in the same age range ... One possible reason for the reduction of synaptic proteins is mitochondrial dysfunction ... researchers believe it's possible that defective mitochondria in Alzheimer's neurons may not move effectively and may not supply adequate levels of Adenosine Triphosphate (ATP). ATP is an important cellular chemical that bonds at nerve terminals for normal neural communication. The low levels of cellular ATP at nerve terminals may lead to the loss of synapses and synaptic function."

Aubrey de Grey Multimedia (April 08 2005)
http://www.mprize.org/index.php?pagename=multimedia
The volunteers at the Methuselah Foundation have been busy of late - here, they have put together a collection of audio and video downloads featuring presentations and interviews with biogerontologist Aubrey de Grey. You'll find appearances at Pop!Tech and the 5th EMBO/EMBL Joint Conference on Science, Society, Time and Aging Mechanisms and Meanings, as well an interview with Janet Street-Porter and a BBC Scotland radio broadcast. If you were wondering just how Aubrey de Grey garners so much interest in his proposed plans for rejuvenative research, here is your chance to find out.

Questing For Dedifferentiation (April 08 2005)
http://www.wired.com/news/print/0,1294,67155,00.html
Wired reports on efforts to replicate the ability of some animals to regenerate entire organs. "Lop off a newt's leg or tail, and it will grow a new one. The creature's cells can regenerate thanks to built-in time machines that revert cells to early versions of themselves in a process called dedifferentiation. Researchers who study this mechanism hope one day to learn how to induce the same 'cell time travel' in humans. If the cells go back far enough, they become stem cells, which researchers believe hold promise for treating many diseases. ... In newts and some other animals with the ability to regenerate, cells at the site of an injury can revert to their embryonic stem-cell stage and can become another type of cell in that creature's body."

Muscles and Mitochondrial Decline (April 07 2005)
http://www.betterhumans.com/News/news.aspx?articleID=2005-04-06-2
Betterhumans notes more research linking mitochondrial damage with age-related degeneration - this time in our muscles. "Mitochondrial DNA is essential for the production of adenosine triphosphate (ATP), the chemical energy that cells use to function. Reductions in ATP reduce muscle endurance, which contributes to the muscle weakness and loss of muscle mass associated with aging. ... [Scientists] found that older participants had more DNA damage and reduced mitochondrial DNA abundance, resulting in reduced gene expression and in turn reduced ATP production and less muscle endurance." A number of groups are investigating methods of repairing mitochondrial damage; a very promising line of research for healthy life extension.

Inflicting Cellular Aging On Cancer (April 07 2005)
http://english.donga.com/srv/service.php3?biid=2005040445838
(From donga.com). Korean researchers are claiming a method of suppressing the agelessness of cancer cells. "Professor Cheong and his team separated breast and cervical cancer cells from the body and cultured them for a month before injecting them with MKRN1 genes. As a result, the growing and dividing cancer cells began aging and finally disappeared." MKRN1 acts to degrade telomerase, the telomere-lengthening enzyme that is dormant in most cells, but active in cancer. In cancer cells, "telomerase protects telomeres from being shortened as far as the aging point. Therefore, cancer cells do not get old and continue cell division to spread themselves to other organs." Safely removing telomerase from the equation seems to be a promising line of enquiry for cancer therapies.

Inkjet Tissue Engineering Update (April 06 2005)
http://news.com.com/Paging+Dr.+Inkjet/2100-1041_3-5656823.html
CNET News.com is running an article on progress towards the use of inkjet printing technologies in tissue engineering. "So far, the Manchester group has employed the technique to spray (and grow) human fibroblasts and osteoblasts, the cells responsible for forming, respectively, muscle tissue and bone ... We are interested in tissue engineering cartilage, bone and blood vessels. Skin is an application but not our main focus even if the press have picked it up. My guess would be bone replacement as the first application." Reliable engineering of blood vessels is needed in order to construct larger masses of replacement tissue for age-damaged organs.

On Mental Degeneration (April 06 2005)
http://www.sagecrossroads.net/Default.aspx?TabID=28&newsType=ArticleView&articleId=109
SAGE Crossroads looks at age-related mental decline and what could be done about it. "Contrary to popular belief, 'there is not an inexorable decline in mental function in older people. If you follow [older] people over time, a lot do get worse, but most stay the same--and some get better.' ... A growing body of research is geared toward determining what keeps some people's minds nimble into old age, and how to reproduce that success in the rest of us. Some scientists have identified genes that are associated with successful aging of the brain and hope to find drugs with similar effects. Others have discovered that simpler solutions like mental exercises also might prevent dementia." Pfizer is currently testing ways of replicating a genetic difference found in some of the most mentally capable centenarians.

Stem Cell Trials Proceeding (April 05 2005)
http://home.businesswire.com/portal/site/google/index.jsp?ndmViewId=news_view&newsId=20050401005453&newsLang=en
Trials for first generation adult stem cell therapies are proceeding quietly, as this press release demonstrates. This part of the field is becoming medicine as usual, complete with funny trademarked names for stem cell formulations. "Osiris Therapeutics, Inc. announced today that it has received clearance [from the FDA] to begin enrollment in the first human clinical trial for a stem cell therapy targeted at injured tissue in knee surgery patients. ... In the U.S. alone, approximately 800,000 people each year have surgery to remove a portion of damaged meniscus, a cartilage-like tissue in the knee that acts as a shock absorber. In several large animal studies, [this therapy] has demonstrated the potential to regenerate the excised meniscus, as well as prevent the typical progression to osteoarthritis."

More Osteoporosis Progress (April 05 2005)
http://www.eurekalert.org/pub_releases/2005-04/yu-kro040505.php
EurekAlert reports on more progress towards a complete understanding of biomolecular processes underlying osteoporosis - the serious, widespread condition of age-related bone loss. "Scientists at the Yale School of Medicine identified a molecule in osteoclasts, IRAK-M, that is a key regulator of the loss of bone mass. Osteoclasts are cells that play a major role in the development and remodeling of bone. They originate from the fusion of macrophages and are important mediators of the loss of bone mass that leads to osteoporosis. ... IRAK-M appears to be a key signaling molecule in the prevention of bone loss. In normal mice the level of IRAK-M in osteoclasts is high compared to what is found in macrophages -- and bones are well maintained. Mice that lack IRAK-M develop severe osteoporosis."

Build The Future You Want To See (April 04 2005)
http://www.mprize.org
The future doesn't just happen - we build it through our actions and giving voice to our opinions. Do you want to see a future in which working anti-aging medicine is a reality? In which the degenerative consequences of aging have been greatly slowed or cured? You can do more than simply hope and talk about it; all of us, scientists or not, can contribute to an important research prize initiative working towards these goals. Visit the Mprize website to see how even a modest donation can help to speed research into extending the healthy human life span. For the cost of a cup of coffee a day, you can join The Three Hundred to demonstrate that you are serious about supporting longevity research. So step up to the plate and help to make the future a better place for all of us!

Overview: Full Stem Ahead (April 04 2005)
http://www.sciencenews.org/articles/20050402/bob10.asp
Science News is running a good overview article on stem cell research: its branches, possibilities and history. "The promise [of stem cells] has not been exaggerated. What's been lost in discussion is how long it will take and how difficult it will be for stem cells to live up to their billing ... The challenge of getting stem cells to differentiate reliably [in the lab] is to provide the cells with an identical replica of the chemical signals that the body naturally uses to sway adult and embryonic cells to differentiate. 'The problem is, we don't know what [those signals] are yet. ... Luckily, some adult stem cells save researchers the task of sorting cells or guessing chemical signals. ... For decades, researchers have taken advantage of this quality in treating leukemia patients with bone marrow stem cells.'"

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The Cape Cod Times reports on centenarian studies and the genetics of natural longevity - something that scientists would like to understand and use as the basis for therapies. "Currently in the United States, about one person in 10,000 lives to be 100 ... Perls divides centenarians into three categories: 'delayers,' who have no age-related illnesses until their 80s; 'escapers,' who have no illnesses at 100; and 'survivors,' who had age-related illnesses prior to turning 80. About 15 percent of centenarians are 'escapers' and the remainder are almost evenly divided into 'delayers' and 'survivors.' ... About 90 percent of the centenarians were functionally independent at the average age of 92."

Link: http://www.capecodonline.com/cctimes/secretto10.htm

Boston.com reports on stem cell politics in Missouri: "Last week, the Missouri Senate shelved a bill that would have banned somatic cell nuclear transfer, or so-called therapeutic cloning. ... State senators debated the measure for six hours without resolution last week. The bill's sponsor, Matt Bartle of suburban Kansas City, resisted calls to compromise or, as some Republicans would have preferred, to drop the proposal entirely. ... Dr. William Nieves, a self-described 'born-again Christian' who heads the Stowers Institute for Medical Research, has told legislators that the institute, which is endowed with more than $2 billion, will forgo an expansion and seek out a location 'more favorable to stem cell research' should the anti-cloning measure pass."

Link: http://www.boston.com/news/nation/articles/2005/04/10/in_missouri_gop_is_riven_over_embryonic_stem_cell_research?pg=full

I'm sure you're familiar with conservatism in the gerontology community with regard to serious anti-aging research; Aubrey de Grey's The Curious Case of the Catatonic Biogerontologists gives a good account of this phenomenon - and what can and should be done about it. How does this conservatism manifest itself in terms of research and funding recommendations, however?

The short answer is that conservative gerontologists call for more efforts to understand aging. More aging research in the current fashion in other words; conversatism manifests itself as a fixation on developing an ever more complete picture of the molecular biochemistry and genetics of the aging process. More knowledge is not a bad thing, but conservative gerontologists are unwilling to admit that current levels of knowledge are sufficient to begin research and development of meaningful healthy life extension therapies - the application of this knowledge.

More forward looking, engineering-based proposals (like Aubrey de Grey's Strategies for Engineered Negligible Senescence initiative) differ by stating that we already know enough to make meaningful inroads into real anti-aging research and the development of therapies to extend healthy life span. This is self-evidently true, as a comparison with any other field of medicine should demonstrate. We don't have a complete understanding of cancer (or almost any other medical condition by gerontological standards of "complete understanding"), yet that hasn't stopped the scientific community from producing ever more effective treatments as our level of knowledge increases.

The road to a cure for aging, like the road to a cure for cancer, has many waystations - each representating some level of treatment, some level of extended healthy life spans. Conservative gerontology ignores the existence of those waystations. Can you imagine a world in which cancer research proceeded that way, pure research with no funding invested in application and the development of therapies?

Nanodot notes that advanced nanomedicine of the sort advocated by Robert Freitas will be on the agenda at the EuroNanoForum 2005 conference later this year. Keeping the focus on medium to long term advances in the nanotechnology field has proven to be something of a battle over the past year - advocates and development plans for molecular manufacturing and nanomedical robotics were in danger of being shut out by an industry focused on short term goals such as nanoscale manufacturing and diagnostic tools. It is these long term goals for medical nanotechnology that have the most likelihood of producing large gains in the healthy human life span - so they should be nurtured and encouraged.

Link: http://nanodot.org/article.pl?sid=05/04/07/2030204

An article from Medical News Today explains our current understanding of links between mitochondrial degeneration and Alzheimer's disease: "Proteins involved in brain cell communications, called synaptic proteins, decrease in the brains of Alzheimer's patients when compared to healthy brains from people in the same age range ... One possible reason for the reduction of synaptic proteins is mitochondrial dysfunction ... researchers believe it's possible that defective mitochondria in Alzheimer's neurons may not move effectively and may not supply adequate levels of Adenosine Triphosphate (ATP). ATP is an important cellular chemical that bonds at nerve terminals for normal neural communication. The low levels of cellular ATP at nerve terminals may lead to the loss of synapses and synaptic function."

Link: http://www.medicalnewstoday.com/medicalnews.php?newsid=22500

Dave Gobel of the Methuselah Foundation drew my attention to a WorldChanging commentary on the rather horrible "The Coming Death Shortage" from the Atlantic. I think that the WorldChanging crew give it more respect than it deserves, but make your own mind up.

I do agree that it is good to see pro-death advocates taking the prospects for radical life extension seriously - no-one with an understanding of the field and the way in which progress happens is laughing at these ideas any more. Healthy life extension is coming; the big question is whether or not it will happen fast enough to benefit those of us reading this today. (And whether enough people will step forward and act to make a difference).

Don't forget to read the comments - many are better than the post in terms of addressing the problems and misconceptions in the reviewed article. Remember that in the end any argument against medical research for longer, healthier lives is an argument for forcing millions of people to suffer and die. It's that simple.

UPDATE: Conveniently enough, you can find the full article text posted at the transhumantech Yahoo! group.

The volunteers at the Methuselah Foundation have been busy of late - here, they have put together a collection of audio and video downloads featuring presentations and interviews with biogerontologist Aubrey de Grey. You'll find appearances at Pop!Tech and the 5th EMBO/EMBL Joint Conference on Science, Society, Time and Aging Mechanisms and Meanings, as well an interview with Janet Street-Porter and a BBC Scotland radio broadcast. If you were wondering just how Aubrey de Grey garners so much interest in his proposed plans for rejuvenative research, here is your chance to find out.

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

Wired reports on efforts to replicate the ability of some animals to regenerate entire organs. "Lop off a newt's leg or tail, and it will grow a new one. The creature's cells can regenerate thanks to built-in time machines that revert cells to early versions of themselves in a process called dedifferentiation. Researchers who study this mechanism hope one day to learn how to induce the same 'cell time travel' in humans. If the cells go back far enough, they become stem cells, which researchers believe hold promise for treating many diseases. ... In newts and some other animals with the ability to regenerate, cells at the site of an injury can revert to their embryonic stem-cell stage and can become another type of cell in that creature's body."

Link: http://www.wired.com/news/print/0,1294,67155,00.html

You may recall Aubrey de Grey's EMBO reports article from last month. Well, you can now download audio, video and a powerpoint of his presentation last year at the 5th EMBO/EMBL Joint Conference on Science, Society, Time and Aging Mechanisms and Meanings from the Mprize website. (You may have to scroll down on that page to see it). You'll also find a number of other interesting video clips from the past year - many thanks go to Kevin Perrott and the other volunteers for putting this all together.

The most important meme that healthy life extension advocates are currently working to spread runs something like this:

The current aging research establishment is far too conservative regarding the near future potential of fully funded longevity research, and their conservatism is damaging the prospects for this funding. The human body is merely a very complex machine and aging is just another medical condition. Aging can - and should - be addressed just like any other chronic, progressive, fatal medical condition. New technologies and knowledge mean that high levels of funding for directed anti-aging research will produce radical gains in healthy life span quickly enough to benefit those of us reading this today.

Over the mid to long term, greater adoption of this meme and related ideas will mean greater research funding and greater pressure for progress and legitimacy in longevity research. You can see Ray Kurzweil hard at work propagating his version of this meme in recent media appearances.

Scientists believe that in the future people will be living for ever - because they will find the key to eternal life.

They believe death is merely an engineering problem to be solved and are developing an organisation called the Institute of Biomedical Gerontology to find that key.

Futurologist Ray Kurzweil, who predicted the internet would rise to global dominance when it was still an obscure government communications network in the 1980s, says immortality is on the horizon.

To date gerontology has largely been a cautious and conservative field dedicated to understanding the biology of ageing. But the new immortalist movement takes a wholly different perspective.

...

His optimism is based largely on biotechnology showing the kind of exponential progress that created the information technology revolution, New Scientist reports.

...

"We're 20 years away from the golden era of nanotechnology," says Dr Kurzweil. "I didn't just start making predictions yesterday."

Most mainstream gerontologists, however, are circumspect. "Research on the biology and genetics of ageing is currently at a similar state to cancer research 20 years ago," says Dr Howard Jacobs, a geneticist at the University of Tampere, Finland.

Betterhumans notes more research linking mitochondrial damage with age-related degeneration - this time in our muscles. "Mitochondrial DNA is essential for the production of adenosine triphosphate (ATP), the chemical energy that cells use to function. Reductions in ATP reduce muscle endurance, which contributes to the muscle weakness and loss of muscle mass associated with aging. ... [Scientists] found that older participants had more DNA damage and reduced mitochondrial DNA abundance, resulting in reduced gene expression and in turn reduced ATP production and less muscle endurance." A number of groups are investigating methods of repairing mitochondrial damage; a very promising line of research for healthy life extension.

Link: http://www.betterhumans.com/News/news.aspx?articleID=2005-04-06-2

(From donga.com). Korean researchers are claiming a method of suppressing the agelessness of cancer cells. "Professor Cheong and his team separated breast and cervical cancer cells from the body and cultured them for a month before injecting them with MKRN1 genes. As a result, the growing and dividing cancer cells began aging and finally disappeared." MKRN1 acts to degrade telomerase, the telomere-lengthening enzyme that is dormant in most cells, but active in cancer. In cancer cells, "telomerase protects telomeres from being shortened as far as the aging point. Therefore, cancer cells do not get old and continue cell division to spread themselves to other organs." Safely removing telomerase from the equation seems to be a promising line of enquiry for cancer therapies.

Link: http://english.donga.com/srv/service.php3?biid=2005040445838

CNET News.com is running an article on progress towards the use of inkjet printing technologies in tissue engineering. "So far, the Manchester group has employed the technique to spray (and grow) human fibroblasts and osteoblasts, the cells responsible for forming, respectively, muscle tissue and bone ... We are interested in tissue engineering cartilage, bone and blood vessels. Skin is an application but not our main focus even if the press have picked it up. My guess would be bone replacement as the first application." Reliable engineering of blood vessels is needed in order to construct larger masses of replacement tissue for age-damaged organs.

Link: http://news.com.com/Paging+Dr.+Inkjet/2100-1041_3-5656823.html

SAGE Crossroads looks at age-related mental decline and what could be done about it. "Contrary to popular belief, 'there is not an inexorable decline in mental function in older people. If you follow [older] people over time, a lot do get worse, but most stay the same--and some get better.' ... A growing body of research is geared toward determining what keeps some people's minds nimble into old age, and how to reproduce that success in the rest of us. Some scientists have identified genes that are associated with successful aging of the brain and hope to find drugs with similar effects. Others have discovered that simpler solutions like mental exercises also might prevent dementia." Pfizer is currently testing ways of replicating a genetic difference found in some of the most mentally capable centenarians.

Link: http://www.sagecrossroads.net/Default.aspx?TabID=28&newsType=ArticleView&articleId=109

Biogerontologist Aubrey de Grey recently recorded a debate on the prospects for radical life extension at the Edinburgh International Science Festival. It is currently available as an audio stream from BBC Scotland - get thee hence and listen.

UPDATE: Kevin Perrott has made an MP3 version available for download at the Mprize website.

An article at Forbes takes a look at the effects of wealth on longevity, finding that a) it doesn't make much of a difference in the grand scheme of things and b) any meaningful analysis would have to take into account the host of selection effects. If you're smart and driven enough to get rich, you're probably also someone who takes care of your health.

The billionaires lived 3.5 years longer than average American males. The results would be even more dramatic if we took into account average life expectancies from around the world, since the billionaires on our list are of all different nationalities.

According to a 1999 study in the British Medical Journal, higher income is, in fact, "casually associated with greater longevity." But when it comes to living longer, billionaires may not be that much better off than mere millionaires. "While an extra dollar of income is protective," the study reads, "the amount of protective effect tails off as total income rises."

...

Some studies contend that rich live longer because of intellectual Darwinism. "Social status," Seligman writes, "correlates strongly and positively with IQ and other measures of intelligence, and intelligence correlates strongly with health literacy--the ability to understand and follow a prescription for disease prevention and treatment." This theory is not without evidence: Seligman cites a 2003 study by psychologist Ian Deary of the University of Edinburgh that found mortality rates to be 17% higher for each 15-point falloff in IQ.

Since most of what kills Americans today is chronic disease, health literacy may, in fact, be a key to longevity. Understanding and monitoring risk factors for the major conditions that predispose us to death--heart disease, cancer, diabetes, obesity, high blood pressure--requires a considerable amount of awareness, discipline and foresight.

In any case, simply having great wealth is not going to work wonders for your life span. You'll get a few extra years at most if all you are doing is enjoying the peripheral benefits. One of the hallmarks of this modern world is that the gap in consumer benefits enjoyed by the wealthy and the poor is not as large as you might think, nor as large as it once was. All the advances that would amaze a time traveller from the 1300s are largely available to the first world poor of our time.

There is one thing that wealth does bring, however, and that is the ability to effect change. Wealth is a big lever that can be used to shape the future - it would only take a small fraction of the holdings of the wealthiest 400 people in the world to set serious anti-aging research underway, for example. In other words, the best way to turn wealth into extra healthy years is to fund advances into working anti-aging and longevity medicine rather than simply enjoy the best medicine currently available. One of the goals of healthy life extension advocacy is to make that point clear to the wealthy of the world.

Trials for first generation adult stem cell therapies are proceeding quietly, as this press release demonstrates. This part of the field is becoming medicine as usual, complete with funny trademarked names for stem cell formulations. "Osiris Therapeutics, Inc. announced today that it has received clearance [from the FDA] to begin enrollment in the first human clinical trial for a stem cell therapy targeted at injured tissue in knee surgery patients. ... In the U.S. alone, approximately 800,000 people each year have surgery to remove a portion of damaged meniscus, a cartilage-like tissue in the knee that acts as a shock absorber. In several large animal studies, [this therapy] has demonstrated the potential to regenerate the excised meniscus, as well as prevent the typical progression to osteoarthritis."

Link: http://home.businesswire.com/portal/site/google/index.jsp?ndmViewId=news_view&newsId=20050401005453&newsLang=en

EurekAlert reports on more progress towards a complete understanding of biomolecular processes underlying osteoporosis - the serious, widespread condition of age-related bone loss. "Scientists at the Yale School of Medicine identified a molecule in osteoclasts, IRAK-M, that is a key regulator of the loss of bone mass. Osteoclasts are cells that play a major role in the development and remodeling of bone. They originate from the fusion of macrophages and are important mediators of the loss of bone mass that leads to osteoporosis. ... IRAK-M appears to be a key signaling molecule in the prevention of bone loss. In normal mice the level of IRAK-M in osteoclasts is high compared to what is found in macrophages -- and bones are well maintained. Mice that lack IRAK-M develop severe osteoporosis."

Link: http://www.eurekalert.org/pub_releases/2005-04/yu-kro040505.php

The comparatively long length of the human life span (nowhere near long enough if you ask me, but a good deal longer than other mammals of similar size and weight) poses an interesting problem for evolutionary biologists. You can get a flavor of current thinking on this issue from a recent Tom Kirkwood paper:

Evolutionary considerations suggest aging is caused not by active gene programming but by evolved limitations in somatic maintenance, resulting in a build-up of damage. Ecological factors such as hazard rates and food availability influence the trade-offs between investing in growth, reproduction, and somatic survival, explaining why species evolved different life spans and why aging rate can sometimes be altered, for example, by dietary restriction. To understand the cell and molecular basis of aging is to unravel the multiplicity of mechanisms causing damage to accumulate and the complex array of systems working to keep damage at bay.

So how, we might ask, did humans end up with long life spans? One set of theories revolves around selection effects that stem from the benefits of socialization and society.

Details of how longevity increases over the course of human evolution provides a wealth of information on how human social networks developed.

The number of people living to older adulthood would have allowed early modern humans to pass down specialized knowledge from one generation to another.

Old age would have also promoted population growth and strengthened social relationships and kinship bonds.

One fairly detailed theory is known as the Grandmother Hypothesis - that prolonged lifespan has been selected to increase the reproductive success of offspring. In other words, the ability to help your grandchildren do well is the driving selection mechanism, not the ability to help your children do well. Enough thought has gone into this for an entire book, it seems:

Darwinian theory holds that a successful life is measured in terms of reproduction. How is it, then, that a woman's lifespan can greatly exceed her childbearing and childrearing years? Is this phenomenon simply a byproduct of improved standards of living, or do older women - grandmothers in particular - play a measurable role in increasing their family members' biological success?

Until now, these questions have not been examined in a thorough and comprehensive manner. Bringing together theoretical and empirical work by internationally recognized scholars in anthropology, psychology, ethnography, and the social sciences, Grandmotherhood explores the evolutionary purpose and possibilities of female post-generative life.

While I'm not sure than any of this directly bears on strategies for extending the healthy human life span via improved medicine, it is interesting.

The future doesn't just happen - we build it through our actions and giving voice to our opinions. Do you want to see a future in which working anti-aging medicine is a reality? In which the degenerative consequences of aging have been greatly slowed or cured? You can do more than simply hope and talk about it; all of us, scientists or not, can contribute to an important research prize initiative working towards these goals. Visit the Mprize website to see how even a modest donation can help to speed research into extending the healthy human life span. For the cost of a cup of coffee a day, you can join The Three Hundred to demonstrate that you are serious about supporting longevity research. So step up to the plate and help to make the future a better place for all of us!

Link: http://www.mprize.org

Science News is running a good overview article on stem cell research: its branches, possibilities and history. "The promise [of stem cells] has not been exaggerated. What's been lost in discussion is how long it will take and how difficult it will be for stem cells to live up to their billing ... The challenge of getting stem cells to differentiate reliably [in the lab] is to provide the cells with an identical replica of the chemical signals that the body naturally uses to sway adult and embryonic cells to differentiate. 'The problem is, we don't know what [those signals] are yet. ... Luckily, some adult stem cells save researchers the task of sorting cells or guessing chemical signals. ... For decades, researchers have taken advantage of this quality in treating leukemia patients with bone marrow stem cells.'"

Link: http://www.sciencenews.org/articles/20050402/bob10.asp

LONGEVITY MEME NEWSLETTER
April 04 2005

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

- (Almost) Live From BIOMEDEX
- Fear of Change and the Human Condition
- Discussion
- Latest Healthy Life Extension Headlines

(ALMOST) LIVE FROM BIOMEDEX

April Smith, Methuselah Foundation fundraiser, was at the BIOMEDEX biotech show last week. Aubrey de Grey and S. Jay Olshansky both gave presentations on longevity and aging at the event - not quite a debate, unfortunately. There will be video of Aubrey de Grey's presentation online in due course, so stay tuned. April Smith found the time to compose a pair of entertaining and informative posts:

http://www.mprize.org/blogs/archives/2005/03/and_what_would.html
http://www.mprize.org/blogs/archives/2005/03/live_from_biome.html

"Olshansky didn't take de Grey on when it comes to biology. Instead he tried to convince the audience that radically extended lifespans should not be our goal. Rather, he suggested that we should focus on three things: a) Improving public health b) postponing the period of time when people are in age-related decline c) improving people's functioning right now. ... Now here's where I disagree with Dr. Olshansky: While I think that we should be putting energy and public health into ending obesity, I don't think that we should do that to the exclusion of focusing medical research dollars on a real cure for aging. And I don't think that talking about the foreseeability of radical anti-aging medicine is going to discourage people from taking on the obesity crisis."

Quite. We stand at a very important point in the history of medical research; for the first time we are within reach of intervening meaningfully in the aging process. We should jump at the chance; if we don't direct major funding towards directed anti-aging research then all of us reading this newsletter today will age, suffer and die. That would not be good - and I don't think it becomes any better if we're all thin when it happens.

As always, you can read more about Aubrey de Grey's proposals for the future of serious anti-aging research at his Cambridge University website:

http://www.gen.cam.ac.uk/sens/

FEAR OF CHANGE AND THE HUMAN CONDITION

Is there no state of being so bad that it outweighs the fear of change that lurks in the dark corners of the human condition? A round of articles hit the press in the last week - with titles like "Longevity is Killing Us" and "The Coming Death Shortage" (I wish I were joking about that one, trust me) - to suggest that extending the healthy human life span is a horrible, terrible thing. You can peruse these dubious works of art and my comments at the following pages:

http://www.longevitymeme.org/news/view_news_item.cfm?news_id=1591
http://www.fightaging.org/archives/000438.php
http://www.fightaging.org/archives/000436.php

Advocacy is an inherently frustrating business at the best of times, but never more so than when watching intelligent people arguing for age-related death and suffering as the very epitome of existence. Their points and convolutions could just as well have been made about the consequences of future progress in medical science back in 1900 - we've made great strides since then and the world doesn't seem to have ended, nor has society fallen apart at the seams. One might even go so far as to suggest that the lot of the average person has been greatly improved, and that further improvement lies ahead:

http://www.longevitymeme.org/articles/viewarticle.cfm?page=1&article_id=11

Change is good - especially change brought by improvements in medicine and the lengthening of lives. It is saddening that so many people do not believe this to be 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

Founder, Longevity Meme

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LATEST HEALTHY LIFE EXTENSION HEADLINES

Structure And Control Of Sirtuins (April 03 2005)
http://www.sciencedaily.com/releases/2005/03/050329144030.htm
ScienceDaily reports on progress in understanding how sirtuin enzymes - connected to longevity, metabolism and the mechanisms of calorie restriction - work and can be controlled. "Molecules that mimic nicotinamide and block sirtuin's activity might be useful in treating diabetes, based on Puigserver's recent discoveries. Or the structural clues could be used to do the opposite, to turn up sirtuin's activity, which might restart a tumor suppressor gene called p53 that is erroneously shut off in many cancers. But those are just two examples." One of the reasons this research is funded is that it can be presented as the search for cures rather than the search for longevity - sadly, the stigma is still there for serious anti-aging science.

Our Good Old Days (April 03 2005)
http://observer.guardian.co.uk/comment/story/0,6903,1451123,00.html
In the wake of a number of truly terrible op-ed pieces on increasing longevity, here is a somewhat better column from the Observer. "Certainly there are challenges ahead as lives lengthen. Pensions, for example, need a radical rethink ... But is this really so dreadful, so long as it is introduced fairly? We enjoy longer lives and better health than our grandparents, and continuing in work gives you a better income ... The building of a society that celebrates age is not an act of charity. Combating ageism and its ills is not about 'them and us' - it's 'us and us'. You will be old too. Bend the ears of politicians now and we will all share the benefits. We owe it not only to ourselves but to the generations before us, who fought to overcome the scourge of early death so that we now enjoy the right to become old."

Aging Science At The Smithsonian (April 02 2005)
http://www.nih.gov/news/pr/apr2005/nia-1.htm
Steven Austad is one of the speakers in a six week series of public presentations on aging science at the Smithsonian, starting later this month. While not focused on longevity per se, it's a good example of the way in which longevity and the possibilities of healthy life extension seep into any discussion of aging research. It is also a good example of the degree to which mainstream gerontology and aging research is walled off from any discussion of using this research as a platform for serious anti-aging studies. This has always seemed a little silly - if we're not studying aging because we want to do something about it, then why do the research in the first place?

Towards Artificial Eyes (April 02 2005)
http://www.rxpgnews.com/article_876.shtml
As biotechnology and regenerative medicine advances, scientists are also making strides in the development of complex prosthetics and other artifical replacements for age-damaged body parts. As RxPG News reports, the quest to develop an artifical eye is closer to fruition than you might imagine. Researchers have "published a design of an optoelectronic retinal prosthesis system that can stimulate the retina with resolution corresponding to a visual acuity of 20/80 - sharp enough to orient yourself toward objects, recognize faces, read large fonts, watch TV and, perhaps most important, lead an independent life. The researchers hope their device may someday bring artificial vision to those blind due to retinal degeneration. They are testing their system in rats, but human trials are at least three years away."

Calorie Restriction In The Economist (April 01 2005)
http://www.economist.com/science/displayStory.cfm?story_id=3809652
The Economist discusses recent research into calorie restriction, suggesting that even small reductions in calorie intake have potentially large effects on an organism. "Their [study] suggests that significant gains in longevity might be made by a mere 5% reduction in calorie intake. The study was done on mice rather than people. But the ubiquity of previous calorie-restriction results suggests the same outcome might well occur in other species, possibly including humans. However, you would have to fast on alternate days." Full-press calorie restriction can only extend healthy life span by 30% or so in mice, so my definition of "significant" may be different - but still, interesting research.

Massachusetts Legislative Update (April 01 2005)
http://www.boston.com/news/local/massachusetts/articles/2005/04/01/house_approves_stem_cell_research?pg=full
(From Boston.com). It seems that legislation to approve embryonic stem cell research and therapeutic cloning will pass in Massachusetts. "The state House of Representatives overwhelmingly approved a bill yesterday that promotes embryonic stem cell research in the Bay State, rejecting by a veto-proof margin Governor Mitt Romney's attempt to prohibit a research technique that involves the cloning of human cells." The state Senate has already approved a similar bill by an equally large margin. "Scientists in Massachusetts are already doing embryonic stem cell research. But the bill would remove the current requirement that the researchers get approval from the local district attorney to work with embryos, and would give the state Department of Public Health some regulatory control over their research."

Oh No! Living Longer, How Terrible! (March 31 2005)
http://www.washingtondispatch.com/article_10773.shtml
You'll find a real classic of anti-longevity sentiment at the Washington Dispatch. Living longer, healthier lives, how terrible some people think it would be! Despite years of advocacy and education, many basic errors in thinking about healthy life extension (and society and economics in general for that matter) remain widespread, especially amongst the wonks concerned with social security. This one in particular doesn't seem to understand that longer lives mean longer, healthier lives - and more years of work and savings. The underlying sentiment that it is better for people to suffer and die than to change a broken system is distressingly common. Change happens - in this case, wonderful change leading to longer lives and healthier people. Be prepared for the future and you'll do just fine.

More On Thyroxine Research (March 31 2005)
http://news.bbc.co.uk/1/hi/health/4396495.stm
The BBC has more on recent research into metabolism, healthy life extension and the hormone thyroxine. While the potential of an improved metabolism to lead to a somewhat extended healthy life span is demonstrated by calorie restriction, tinkering with thyroxine on an ad hoc basis - as for any hormone - seems to be a potentially dangerous proposition. "We know thyroxine affects your metabolic rate. The key is getting the right dose. ... Having an over-active thyroid gland puts you at a three-fold risk of potentially fatal heart disorders and a three to four-fold risk of osteoporosis. An over-active thyroid causes considerable morbidity in the ageing population. ... he warned people who had even a slightly higher level of thyroxine were at risk of ill health."

Current Longevity Research (March 30 2005)
http://www.indianexpress.com/full_story.php?content_id=67428
The Indian Express surveys the better known longevity research currently taking place around the world: genetic engineering, calorie restriction mimetics and various means of preventing damage caused by free radicals produced by our metabolism. What all these strands of research have in common is that they are most likely not the best way forward to a cure for aging. While this research may lead to a few decades of extended healthy life span by slowing age-related degeneration, it do not go anywhere near as far as is thought to be possible. Biogerontologist Aubrey de Grey argues, for example, that it is at least as easy to reverse aging as it is to simply slow it.

A Cure For Arthritis? (March 30 2005)
http://www.nature.com/news/2005/050328/full/050328-6.html
Nature reports that scientists have brought osteoarthritis, an all too common age-related condition, to a halt in mice: "The researchers investigated a family of enzymes, called aggrecanases, that are thought to contribute to osteoarthritis by chewing up a vital component of cartilage that makes it tough and elastic. The teams showed that mice genetically engineered to lack a working form of one such enzyme, ADAMTS5, seem impervious to arthritis. ... Various enzymes come and go and all turn out to be dead ends. But now we might be on to something. ... The researchers are particularly hopeful because the mice lacking the working enzyme showed no signs of problems elsewhere in their bodies."

Pluripotent Stem Cells Everywhere (March 29 2005)
http://www.betterhumans.com/News/news.aspx?articleID=2005-03-28-3
Betterhumans notes more progress in the discovery and manipulation of pluripotent adult stem cells. "Stem cells from hair follicles can develop into neurons, muscle and more, suggesting that hair is a potent and accessible source of cells for regenerating tissues." Judging from progress to date, I would expect to see more reserves of potentially very useful stem cells found in the adult body - research into regenerative medicine should benefit accordingly. Therapies most likely to be accelerated by this and similar lines of research are those aiming to replace comparatively small populations of damaged cells in the body - good examples of the type are cures for age-related diabetes or Parkinson's.

Why Cryonics? (March 29 2005)
http://www.kuro5hin.org/story/2005/3/22/13539/6192
You'll find a good essay on the history, practice and science of cryonics over at Kuro5hin. "Together, function and structure allow for life. Cryonics does not preserve all biological functions - vital functions like brain activity and heart-beat are over when modern medicine pronounces a person dead. But cryonics does preserve structure, and this is what makes it so important as a life-saving procedure. It may seem fanciful that death can be stopped as a result of cryonics, but the practice has scientific support." Cryonics is an experiment with an uncertain chance of success - but it is the best option open for the unfortunate millions who will die from age-related degeneration before real anti-aging medicine can be developed and deployed.

Recent Progeria Research (March 28 2005)
http://www.keralanext.com/news/indexread.asp?id=165525
KeralaNext.com provides a good summary of recent research into Hutchinson-Gilford Progeria Syndrome, a condition of greatly accelerated aging. The genetic cause was recently identified - this offers hope for a cure in the years ahead, as well as increased understanding of the normal aging process. "Low levels of HDL, or the 'good' cholesterol, play a role in the development of heart disease in children with progeria. ... Dr. Smoot said that the next step in research will be to understand the relationship between the lamin A protein and HDL cholesterol levels. Such research, she said, could have 'huge implications for everybody. Aging and heart disease are the two most significant issues for most people in Western society, so anything we learn along the way might provide clues for the general population.'"

Your Financial Future And Longevity (March 28 2005)
http://news.ft.com/cms/s/2833a776-9f7f-11d9-b355-00000e2511c8.html
The Financial Times is running an alternately insightful and obtuse article on increasing longevity and what that means for personal finance and over-regulated pension or social security schemes. As is all too common in this sort of article, increased longevity is presented as a bad thing due to the changes it will bring. Living healthily for longer, how terrible the bean counters think it would be! This is an excellent example of the way in which systems come to be given more weight and priority than the people they are supposed to serve. The lesson here is to plan your future under the assumption that the idiots in charge do not have your best interests in mind and are not going to be around to pick up the pieces.

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I've directed a fair amount of the focus of the Longevity Meme and Fight Aging! towards stem cell research and related regenerative medicine over the past few years. It has been the largest and most obvious battle over freedom of research, a topic I think is very important for long term progress. In addition, stem cell technologies will help - directly or indirectly - to extend healthy life span in the years ahead. Cures for common age-related diseases are the direct approach, though this is not as helpful as you might think from the point of view of extending maximum life span. Any number of other age-related conditions lurk, waiting to be discovered as our life spans grow longer. Cures for cancer, diabetes, Alzheimer's and so forth will add years for those who would have suffered and died, but don't do much to the underlying processes of aging that limit our maximum life span.

The knowledge we gain regarding the biochemical and genetic workings of our cells in the course of stem cell research is pure gold - it will speed, assist and enable all sorts of research into finding and addressing the mechanisms of the aging process. We don't want to find out (the hard way) about new age-related conditions that lie beyond Alzheimer's. Rather, we want to learn to halt the aging process in its tracks; prevent degeneration and damage or repair it as it happens so that we don't have to devise ever more complex strategies to deal with the end results of aging.

But back to the battle over stem cell research: think it's safe to say that we're over the hump. Most people are aware of (and comparatively well educated about) the benefits of stem cell research, funding is widely supported and anti-research legislation opposed. There were only a few noteworthy advocates a few years ago - now there are well-organized hundreds ... and news sites, blogs, press attention and all that goes with it. The battle continues, but I think that anti-research groups have as good as lost - the forces arrayed against them are too strong; it is human nature to grasp at new medicine with both hands once the benefits are clear. The worst that the anti-research groups can do is to continue to delay the development of stem cell based therapies for age-related conditions - a little here, a little there.

Overall, this means that I will be spending more time in the future on aging and longevity rather than stem cells - unless there is direct relevance. Stem cell research and advocacy is well underway, but serious anti-aging research is not. However well things are going elsewhere in the world of medicine, that remains a big problem.

ScienceDaily reports on progress in understanding how sirtuin enzymes - connected to longevity, metabolism and the mechanisms of calorie restriction - work and can be controlled. "Molecules that mimic nicotinamide and block sirtuin's activity might be useful in treating diabetes, based on Puigserver's recent discoveries. Or the structural clues could be used to do the opposite, to turn up sirtuin's activity, which might restart a tumor suppressor gene called p53 that is erroneously shut off in many cancers. But those are just two examples." One of the reasons this research is funded is that it can be presented as the search for cures rather than the search for longevity - sadly, the stigma is still there for serious anti-aging science.

Link: http://www.sciencedaily.com/releases/2005/03/050329144030.htm

In the wake of a number of truly terrible op-ed pieces on increasing longevity, here is a somewhat better column from the Observer. "Certainly there are challenges ahead as lives lengthen. Pensions, for example, need a radical rethink ... But is this really so dreadful, so long as it is introduced fairly? We enjoy longer lives and better health than our grandparents, and continuing in work gives you a better income ... The building of a society that celebrates age is not an act of charity. Combating ageism and its ills is not about 'them and us' - it's 'us and us'. You will be old too. Bend the ears of politicians now and we will all share the benefits. We owe it not only to ourselves but to the generations before us, who fought to overcome the scourge of early death so that we now enjoy the right to become old."

Link: http://observer.guardian.co.uk/comment/story/0,6903,1451123,00.html

Steven Austad is one of the speakers in a six week series of public presentations on aging science at the Smithsonian, starting later this month. While not focused on longevity per se, it's a good example of the way in which longevity and the possibilities of healthy life extension seep into any discussion of aging research. It is also a good example of the degree to which mainstream gerontology and aging research is walled off from any discussion of using this research as a platform for serious anti-aging studies. This has always seemed a little silly - if we're not studying aging because we want to do something about it, then why do the research in the first place?

Link: http://www.nih.gov/news/pr/apr2005/nia-1.htm

As biotechnology and regenerative medicine advances, scientists are also making strides in the development of complex prosthetics and other artifical replacements for age-damaged body parts. As RxPG News reports, the quest to develop an artifical eye is closer to fruition than you might imagine. Researchers have "published a design of an optoelectronic retinal prosthesis system that can stimulate the retina with resolution corresponding to a visual acuity of 20/80 - sharp enough to orient yourself toward objects, recognize faces, read large fonts, watch TV and, perhaps most important, lead an independent life. The researchers hope their device may someday bring artificial vision to those blind due to retinal degeneration. They are testing their system in rats, but human trials are at least three years away."

Link: http://www.rxpgnews.com/article_876.shtml

A little science coverage relating to calorie restriction mimetics today for those of you who like to keep a close eye on such things; this post was made by Pete Estrep on the Gerontology Research Group list:

I'm not sure how tuned in to the Sirtuin/resveratrol controversy GRG members are (I know some eavesdroppers/lurkers know the scoop) but this is turning into the biggest head scratcher in aging research. Here are the basics. While in Lenny Guarente's lab at MIT, Longenity co-founder Matt Kaeberlein discovered the life extension effects in yeast of a protein called Sir2. Guarente's lab showed that Sir2 is a NAD-dependent deacetylase and Guarente and Heidi Tissenbaum showed lifespan extension of nematodes overexpressing Sir2. Several labs, including Guarente's and Dave Sinclair's at Harvard went on to show that Sir2 has several interesting properties. Some of the most interesting research has come from a collaboration between Sinclair's lab and BIOMOL Research Laboratories in Pennsylvania, the makers of in vitro assay products for Sirtuin activity. Using the BIOMOL assay several Sirtuin Activating Compounds (STACs) have been identified, one of which is resveratrol. Sinclair showed that resveratrol increases yeast replicative lifespan, and then together with Marc Tatar and Steve Helfand, they showed that resveratrol extends lifespan in nematodes and fruitflies. Resveratrol looks very exciting, right? Well, things have gotten interesting in the past few months.

Matt Kaeberlein, who is now back in academia at the University of Washington, recently published two papers with Brian Kennedy and Stan Fields. One shows that the lifespan-extending effects of Sir2 in yeast are strain dependent, that calorie restriction of yeast extends lifespan more than Sir2 overexpression, and that this effect is Sir2 independent.

The more recent publication shows that the in vitro assay used to assay Sir2 function is faulty, that resveratrol activation of Sir2 is an artifact, and that resveratrol has no effect on Sir2 activity in vivo, as measured by rDNA recombination, transcriptional silencing near telomeres, and replicative lifespan (Kaeberlein M, McDonagh T, Heltweg B, Hixon J, Westman EA, Caldwell S, Napper A, Curtis R, Distefano PS, Fields S, Bedalov A, Kennedy BK. Substrate specific activation of sirtuins by resveratrol. J Biol Chem. 2005 Jan 31; [Epub ahead of print] PMID: 15684413. The in vitro artifact has been confirmed by another group at the University of Wisconsin ( Borra MT, Smith BC, Denu JM. Mechanism of human SIRT1 activation by resveratrol .J .Biol Chem. 2005 Mar 4.). So, at least three groups have shown lifespan extension by resveratrol in yeast, worms, and flies, and it is claimed that resveratrol is acting by binding to and directly activating Sir2; and now two groups have shown that this binding is an artifact and Kaeberlein and colleagues have shown that the lifespan extension also appears to be an artifact.

Now, to further complicate things, Parker and colleagues (Parker, J. et al. Nat. Genet. 37, 349-350 (2005) have presented data suggesting that resveratrol moderates the symptoms and is neuroprotective in two models of Huntington's disease, and this effect is Sir2 dependent. Are you confused yet? Me too, along with everyone else in the field. Stay tuned for new developments.

While I'm not voting this "biggest head scratcher" (that would be reserved for why serious longevity research is so underfunded), it is certainly interesting. It seems that research groups are on the verge of pulling the various threads together - this sort of confusion and contradiction is very indicative of progress in science. A more accurate picture of this facet of our metabolic processes and its interaction with healthy life span can only be beneficial. It is plausible that we could obtain an extra decade or two of additional healthy life span from the application of modern biotechnology to improving our metabolism. This may not be radical life extension, but it is certainly better than nothing.

The Economist discusses recent research into calorie restriction, suggesting that even small reductions in calorie intake have potentially large effects on an organism. "Their [study] suggests that significant gains in longevity might be made by a mere 5% reduction in calorie intake. The study was done on mice rather than people. But the ubiquity of previous calorie-restriction results suggests the same outcome might well occur in other species, possibly including humans. However, you would have to fast on alternate days." Full-press calorie restriction can only extend healthy life span by 30% or so in mice, so my definition of "significant" may be different - but still, interesting research.

Link: http://www.economist.com/science/displayStory.cfm?story_id=3809652

(From Boston.com). It seems that legislation to approve embryonic stem cell research and therapeutic cloning will pass in Massachusetts. "The state House of Representatives overwhelmingly approved a bill yesterday that promotes embryonic stem cell research in the Bay State, rejecting by a veto-proof margin Governor Mitt Romney's attempt to prohibit a research technique that involves the cloning of human cells." The state Senate has already approved a similar bill by an equally large margin. "Scientists in Massachusetts are already doing embryonic stem cell research. But the bill would remove the current requirement that the researchers get approval from the local district attorney to work with embryos, and would give the state Department of Public Health some regulatory control over their research."

Link: http://www.boston.com/news/local/massachusetts/articles/2005/04/01/house_approves_stem_cell_research?pg=full

I am compelled to direct your attention to yet another entertaining high-quality post from Methuselah Foundation fundraiser and calorie restriction practitioner April Smith.

So I was expecting to walk up to Jay Olshansky after the debate and start a happy chat about how much better everything would be if lots and lots of people would do at least moderate CR. I pointed out that CR will get us most of the benefits he outlines in his three goals, and that Luigi Fontana is studying CR'd humans and finding excellent health results. ... Dr. Olshansky then said, "But what you're on is an experimental diet."

"So is whatever you ate today," I answered.

As you might have gathered, April has been at the BIOMEDEX show alongside Aubrey de Grey to talk up the Mprize for anti-aging research. I eagerly await video and transcripts of the debate between de Grey and Olshansky...