$36,000
$24,120

Diagnostic Nanomedicine Well Under Way

(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

How Much Can Be Done In 25 Years?

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!

Unique, Personalized Medicine

(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

More Like Salamanders

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

Massachusetts Stem Cell Bill Passed

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

Those Guidelines for Human Embryonic Stem Cell Research

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.

The Future of Open Source Biotechnology

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.

More Years, More Cancer, More Therapies

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

Telomere Complexities

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

Early Regenerative Therapies Advancing

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

More On Exercise Versus Alzheimer's

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

Brian Delaney on Calorie Restriction and That Weight Study

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.

The Longevity Meme Folding@Home Team

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!

On Healthy Life Extension

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

Hibernation Research Funded

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

Talking About the Pope (Again)

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.

Towards An Alzheimer's Gene Therapy

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

Calorie Restriction / Protein Restriction

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

A Short Quote

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.

The Near Future Of Medicine

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

A Long-Term Aging Study

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

Keeping Stem Cells Totipotent

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

Adult Stem Cells And Cancer Risk

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

The Other Half of the Fight Against Infectious Disease

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.

More Neurodegenerative Trials

(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

A Look At Alzheimer's Research

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

What To Do With Induced Hibernation?

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.

Better, Faster Bone Generation

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

More On Making Cancer Age

(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

Healthy Life Extension and Life Terms

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?

On Being a Sensible Scientific Conservative

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.

A Good Idea, Slowly Spreading

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

Inside A Stem Cell Therapy Trial

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

Thought for the Day

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.

Promising Gene Therapy For Blindness

(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

Towards More Human Trials

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

Point Mutations, Mitochondria and Aging

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.

Evaluating Longevity Genes

(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

More On Wealth And Longevity

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

Bidding With Public Funds

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

Longevity And Future Health Costs

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

Those Irrepressible Errors

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.

Aging And Calorie Requirements

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

Wound Healing Gene Identified

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

Stem Cell Legislation Overview

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

Searching For The Root Of Cancer

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

Steven Austad for President

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.

Regenerate 2005

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/

Crafting New Bone

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

Welcome to the Immortals' Club

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 Deep Divide

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.

Alzheimer's Antibody Progress

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

Ronald Bailey On "Death Shortage"

(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

Sifting For Stem Cells

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

Linking SENS and Regenerative Medicine

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).

34th Annual AGE Meeting

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

Discussing the Evolutionary Theory of Aging

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.

Profiling Bob Klein

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

The 25 Year Timeline

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

More On Centenarian Studies

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

No Missouri Research Ban?

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

Manifestations of Conservatism in Gerontology

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?

Nanomedicine At EuroNanoForum

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

Alzheimer's And Mitochondria

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

More Commentary on "The Coming Death Shortage"

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.

Aubrey de Grey 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.

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

Questing For Dedifferentiation

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

More Aubrey de Grey Audio and Video Downloads

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 Important Meme

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.

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

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"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.

Muscles and Mitochondrial Decline

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

Inflicting Cellular Aging On Cancer

(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

Inkjet Tissue Engineering Update

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

On Mental Degeneration

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

Wealth and Longevity

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."

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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.

Stem Cell Trials Proceeding

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

More Osteoporosis Progress

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

Evolution, Longevity and the Grandmother Hypothesis

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.

Build The Future You Want To See

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

Overview: Full Stem Ahead

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

On Stem Cell Research

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.

Structure And Control Of Sirtuins

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

Our Good Old Days

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

Aging Science At The Smithsonian

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

Towards Artificial Eyes

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

Pete Estrep on Recent Research

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.

Calorie Restriction In The Economist

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

Massachusetts Legislative Update

(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

What *Did* S. Jay Olshansky Eat Yesterday?

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...