The transcript is up for the July 19th SAGE Crossroads webcast entitled "Alzheimer's Research and Basic Science of Aging: Is There a Better Balance?" This opening commentary sums up what many people are thinking about budget priorities in public funding right now:

I imagine a sort of a fantasy where I would go into the office of the chief of the National Institutes of Health and tell him or tell her, “Look, we've got a treatment. It works in mice and rats. We don't know how it works. But it knocks down the incidence of breast cancer by 90 percent.” I imagine I would get a very pleasant smile and a handshake and someone who wants to listen to me further.

Then I say, “Well, there's a side effect. It also slows down the rate of brain aging and cataract development.” And I would be told, “That's great news indeed! We should work on this further.”

And then I'll say, “Well, there's something else I forgot to mention; all of the other kinds of cancers and immune failure and muscle failure—these also are delayed by 90 percent.”

At this point the person who's in charge of this conversation, in charge of NIH, says, “Wait a minute. You are talking about slowing down aging. Everyone knows that can't be done.”

That's an old paradigm and I think it's time to change it. The basic message I'm hoping to bring to this discussion is not that one kind of research on Alzheimer's or breast cancer or AIDS or multiple sclerosis or Parkinson's is bad, or that we are doing too much of it. The perspective I want to bring to the discussion is that the best way, the most likely way to postpone and to put off all of those diseases put together, is aging research.

I think it's a scandal that of every hundred bucks the National Institutes of Health devotes to funding scientific research, only six cents go to fundamental research on the biology of aging. Since it's the only method we now having for slowing all of these multiple diseases of aging, Alzheimer's very likely among them, I think that deserves far more attention that it's now getting.

It's the best way to make progress in conquering most of the diseases of aging that afflict us as we get older.

Prevention versus cure is a fairly old argument in medical research circles: I fall into the camp that believes far too little effort goes into the former strategy.

It has to be said that many of the recent SAGE Crossroads webcasts have turned out to be discussions on what should be done rather than actual debates - both sides agree on the basics and are talking about the details in a friendly way. This latest webcast does exhibit some big differences of opinion, even though the fellow arguing the Alzheimer's research side notes:

I think this won't be so much a disagreement as a love fest on aging, as I mentioned when we were chatting a bit earlier, because I, too, believe that aging research needs more support. It would be disingenuous to argue otherwise. I am, after all, the director of the Institute on Aging at Penn, as well of our Alzheimer's Disease Center. In fact, I have lobbied successfully to our dean, Arthur Rubenstein, to commit $5 million to aging research at the University of Pennsylvania.

The funding levels are certainly different, however, and I don't believe that a dollar spent on Alzheimer's research at this time is as well spent as a dollar on basic aging research.

Well, I believe that we have far too little funding for basic aging research. When the Alzheimer's folks talk money, they add a couple zeros to the amount of dollars that I get to talk about. John is able to say, “Oh, you add another $100 million here, another $100 million there.” A $100 million represents roughly ten years' worth of spending on the biology of aging for the NIA budget.

This weekend, Spiderman II brought in $180 million in ticket receipts in its first six days of performance. So any one day's receipts for Spiderman represents five years of basic aging research.

I think that represents a society that hasn't really thought hard about where funds ought to be applied. If I had been having this conversation with you fifty years ago, I would have been faking it because fifty years ago people didn't know if aging could be slowed, and they didn't know if they could slow it—whether what you'd get is people who just have Alzheimer's disease or chronic debility or osteoporosis for most of their lives.

But now we know the answer.

But go ahead and read the rest of it. There's some interesting stuff in there, and it's always entertaining to watch people stretching to defend their budget. I'll leave you with this thought:

The aging process is such a powerful determinant of all the late-life diseases, that even a very modest ability to slow it down will have a more profound effect on health in this country and elsewhere than conquering not only one of the diseases, but effects on all of the diseases put together.

Posted by Reason at 12:19 PM
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The Scientist published a long piece on trials in regenerative medicine using fetal cells in China:

Over the past 3 years, Huang told The Scientist, he has used fetal tissue transplants to treat more than 450 patients. He now has 1000 Chinese and foreign patients on a waiting list, including about 100 Americans, who find him via the Internet or word of mouth. He has also used the procedure to treat strokes, multiple sclerosis, cerebral palsy, and brain injuries with, he says, "equally positive results."

The bulk of his Huang's patients are people suffering from spinal cord injury, followed by ALS, a distant second. He has only treated a few patients with Parkinson disease.

Some of the technical details:

Huang uses olfactory ensheathing glial cells (OECs) extracted from the olfactory bulbs of fetuses aborted during the second trimester of pregnancy. These cells are thought to have the capacity to regenerate damaged nerve fibers, and although research groups elsewhere are conducting human trials with adult versions of the cells, Huang's group is virtually alone in using fetal tissue.

The neurosurgeon's team cultures the cells before injecting them into the patient.

...

The transplanted cells do not replace neurons, but help the neuronal axons to regenerate, and this brings about improvements in the conditions of patients, Huang told The Scientist. "OECs don't replace neurons," he said. "It's the glial cells that provide an environment in which damaged neuron cells recover."

"I don't know how it works, but I know it helps patients," the neurosurgeon admitted. "But the clinical evidence shows that it can help. And if I'm wrong, we wouldn't be achieving these results."

Fetal tissue research is restricted in the US and Europe, which is why it is left to researchers in China to perform this sort of work. Some Western groups are evaluating Huang's research to see what we can learn from it, and whether more sophisticated and well controlled trials can proceed:

Wise Young, a research professor at New York University's medical school, told The Scientist Huang's work was interesting. "His results represent a credible phase 1 trial that establishes the safety and feasibility of such transplants. Preliminary analyses of the results suggest that the procedure may produce rapid but modest sensory and motor improvements in people from 2 to 40 years after injury. These results await confirmation with more rigorous controlled trials."

Huang himself does not claim a miracle cure. With spinal injury patients, he said, neurological functions can improve, but he expects no complete recovery. With ALS, "If the process can keep them stable, that's already pretty good."

Huang has published some of his results in a medical journal. They provide an incentive for researchers working in this and related areas to make progress towards understanding why this therapy works - and to build better therapies from the underlying biochemistry.

Posted by Reason at 1:50 PM
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I don't have much spare time for posting today: I'm taking a last look over the manuscript of "The Scientific Conquest of Death: Essays on Infinite Life Spans" before it heads off to the folks at the printer for formatting and other mysteries of the trade.

Collaborating over the Internet to produce a book of essays on healthy life extension, immortality and related philosophical matters has certainly been an interesting experience. It just goes to show what you can accomplish when you put your mind to it; the book contains great essays by well known people in the field. We're planning a second volume already...

Posted by Reason at 9:52 PM
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Politics is a black hole, it really is. Politicians have no powers other than those of destruction, harassment and hinderance - and like classic thugs they use their power to suck everyone into circus events and the fight over spoils. If all the dollars put into the destructive work of centralizing power and then fighting over it were instead put into serious anti-aging research or educating people about healthy life extension, how far could we go? A long way, I think.

Brian Doherty of Reason Online has written an excellent piece to remind us of the power of walking away from politics:

Nothing like this week of all-Kerry-all-the-time Democratic convention coverage to turn one's mind to the other side of life—you know, the side not directly connected to the system of coordinated violence and threats designed to force other people to do what you want them to, and people's attempts to game that system in a usually futile attempt to "make a difference."

...

The experience of researching and writing the book exposed me to many vivid, inspiring examples of the wonderful and unprecedented things that can, and do, happen when people work, not on national politics, but on their own lives, with their own friends, within their own self-created communities—things that enrich their lives as well as, often, the lives of many, many others.

Little comes out of throwing your support behind candidates except further support for a system of petty controls and evil tyranny. Believers in progressive politics who are interested in the arts and experiments-in-living, as they so often are, have much more to offer the world—and, if I may be so bold, their own lives—by producing art and experiments in living rather than indulging in electoral politics.

Progress, creation, good lives and better medicine don't come from politicians. They do not create or build - all they do is shout, threaten, tear down, abuse the power we give them and lay down roadblocks on the way to the future.

The people who try to forge something new—whether an object, or a technology, or a way of life—will change and benefit the world far more directly than any conventioneer or politician is likely to, and probably have more fun doing so. As Alexander Cockburn recently and correctly noted, the quality of life of his (mostly lefty) readership in terms of coffee, bread, and vegetables has improved enormously in the past 30 years. And it was not thanks to any government initiative. And what we eat and drink everyday, in a healthy life, ought to mean much more to us than the machinations of those in Washington.

Where do we live? We live with ourselves and with other people, both in person and virtually; we live with our work; we live with the objects of cultural production that help us make sense of our lives and our work, or merely, in ways often indefinable even to ourselves, delight and divert us. We ought not, to the extent we can help it, live in George Bush's America, or John Kerry's.

We should shun politics and the parasites who live in that world. We should turn our backs on politicians and rent seeking. We should instead focus on our own lives - building the future we wish to see through our work and ingenuity. It is better that our dollars and time go to our own individual visions than to bolster one or other of the competing gangs in government.

My vision is for a future in which aging and age-related conditions are defeated and cured. I work with groups like the Methuselah Foundation and the Immortality Institute to help lay a small part of the groundwork for that future. I talk to the media to help raise the profile of serious anti-aging and healthy life extension research. I provide resources for people who want to learn more about the healthy life extension community and broader topics like cryonics or calorie restriction.

While I do comment on politics - and encourage those who do want to be involved in the political arena to speak out against restrictive legislation - I am far more involved in and pleased with my constructive nonprofit work. The Methuselah Mouse Prize has passed $400,000 in cash and pledges. The Immortality Institute is publishing a book this year and a documentary film project is underway. Extending the healthy human life span is taken much more seriously in the press and given far more attention than even just a few years ago. Of course, I am fortunate to be doing this work at an auspicious time and in the company of many other advocates - but I'm doing my part in the fight to cure aging and all age-related disease.

How about you?

Posted by Reason at 12:11 AM
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There have been lot of stem cell research and politics articles in the news of late. In the runup to the US presidential election in November, the Democrats are positioning themselves as the party of stem cell research:

John Kerry said Monday that America needs a president who "believes in science" and supports stem-cell medical research.

The Bush administration has limited federal funding of research on stem cells that results in the destruction of a living human embryo. But Kerry said he'd promote stem-cell science that could aid people with Alzheimer's and Parkinson's diseases and diabetes. "We need to push the curve of discovery," he told 400 Floridians at a NASA visitor center near the space shuttle launch pads.

The current convention is being used as a springboard:

"Stem cell research is about the quality of life of humans," said state Sen. Wayne Bryant, D-Lawnside. "We ought never forsake the ability to correct and prevent medical problems."

Bryant said that in New Jersey, in particular, where Gov. James E. McGreevey has already created the nation's first state-supported stem cell institute, such authorization would not only lead to advances in the medical field, but also produce a "whole new industry."

Tonight, in one of the most thumb-in-your-eye moments of the convention, Ronald Reagan's youngest child will criticize President Bush's position on stem cell research.

Former President Reagan - nothing less than an iconic figure for GOP conservatives - died in June after a decade-long struggle with Alzheimer's disease. Many researchers believe that stem cell research could unlock cures for that debilitating illness and a host of other deadly and crippling diseases.

As an aside on the connection between Alzheimer's research and embryonic or adult stem cell research, I think Chris Mooney summarizes the situation well:

I think this story from the Scientist, from a while back, gives a very balanced take on the question. The article begins by noting that "most in the field admit it's highly unlikely that a stem cell transplant could cure or even treat Alzheimer's." Conservatives are right on this point. But then they miss the bigger picture: Even if transplants probably won't work, embryonic stem cell research could yield a wealth of information about Alzheimer's that could be productive in leading to treatments down the road.

...

As you can see from this, the question of the future of Alzheimer's research is very much on the table when the embryonic stem cell issue gets debated. Those who leap from the notion that ES cells won't cure Alzheimer's through transplants to the idea that they're absolutely worthless for all things related to Alzheimer's appear to be either ignorant of the science or willfully missing the big picture.

In fact, you'll find a whole array of great posts over at the Intersection:

The NIH on Adult Stem Cells:

Continuing my flurry of campaign-oriented stem cell research posting, consider the following. It so happens that the National Institutes of Health has a position on adult stem cells, and it's one that political boosters of studying these cells to the exclusion of embryonic stem cell research won't take kindly to.

The Union of Concerned Scientists and Stem Cell Research:

It's odd, isn't it? In all of their important critiques of the Bush administration, I'm not aware of any place or occasion when the Union of Concerned Scientists have centrally discussed the stem cell issue.

...

After all, I happen to know that many of the UCS statement signatories, including Nobel Laureates Paul Berg and David Baltimore, care a lot about embryonic stem cell research. To say nothing of Gerald Fischbach. Still, it's odd that UCS hasn't ever really brought up the matter.

Meet Gerald Fischbach:

"It's hard to stop science," he says. "The first breakthrough, the first patient that really benefits from stem cell therapy, will change everything. It will be irresistible in terms of public demand and recognition."

Of course, Chris Mooney talks about the Democratic convention in the context of the political debate over stem cell research:

My prediction is that the growing emphasis on the relationship between politics and science will only add to the attention garnered by this top political science issue. Back in the summer of 2001, no one knew that Bush II would go on to enrage scientists so profoundly. Now, instead of complaining about widespread meddling with obscure advisory panels, the embryonic stem cell research issue can serve as a sweeping proxy for their discontent.

...

Nevertheless, embryonic stem cell research potentially touches the lives of more than a hundred million Americans, through their familial ties to those suffering from one or more of the diseases embryonic stem cell research may impact. That's a staggering number of people who either care or could be made to care about the issue.

But enough politics. I'll just note this piece on public support for stem cell research:

On June 11, 2004, the nonprofit and nonpartisan Results For America (a project of CSI) released a national opinion survey showing that, by a decisive margin of 74-21 percent, the vast majority of Americans support former First Lady Nancy Reagan’s call for the Bush White House to lift restrictions on stem cell research in order to look for possible treatments for the Alzheimer’s disease that afflicted former President Ronald Reagan prior to his recent death, as well as the other grave illnesses – including diabetes, Parkinson’s, heart disease and multiple sclerosis.

Solo said: "The death of Ronald Reagan altered the course of the national dialogue about stem cell research. When almost three out of four Americans say that they now are more likely to support stem cell research, what you are witnessing is a fundamental shift in the way that average Americans think about this issue. It would be a shame and a potentially devastating setback for the progress made in support for stem cell research if it becomes some sort of litmus test for political parties during the 2004 elections."

I'll finish up by reminding everyone that 2000 US citizens die each and every day from heart disease, a condition shown to be treatable using even comparatively crude stem cell therapies. Regenerative medicine based on stem cell research (adult and embryonic) has the potential to produce effective treatments for most age-related degenerative conditions.

It is a great pity that we live in a world in which politicians have such an enormous negative influence over our future health, longevity and access to advanced medicine. We should do something about that.

Posted by Reason at 12:09 PM
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I mention some of my thoughts on priorities, supplements, and the likely nature of meaningful future anti-aging technologies in the latest Longevity Meme newsletter. As we all know, I'm not that hot on the amount of (media and community) attention lavished on supplements and pills when serious anti-aging science is languishing for lack of support.

I was planning on posting a followup here today regarding balance in our approach to the future and health, but Ian Clements beat me to the punch in an e-mail communication. So I'll let him to do the talking:

You keep saying that a pill is not the answer - how do you know (as distinct from believe)? Whilst I share your scepticism about a pill being the answer, I'm sufficient of a scientist not to be certain about anything about the future - empiricists use evidence, not belief, as their criterion.

More importantly, taking pills is not mutually exclusive to doing all the other things to extend life and improve health (we both seem to agree on that).

The problem I, and, I suspect, most others face, is attempting to keep fit and healthy whilst staying cautious - waiting too long until all the evidence is in is to maybe delay too long the benefits. This necessarily applies when the science is moving only as fast as I am ageing! It is a balance of risk - hoping that the risk is minimal or non-existent for adopting what turns out to be false ideas and possible major advantages if they are right. We've all seen this for vitamins; smoking; diet and exercise. Sure there's been blind alleys, wrong turns even (avoiding all fat as much as possible being a recent example), but I suspect that those of us who've attempted to follow the best science at the time have stayed ahead of the curve despite these errors (all too-often pointed out by dubious relatives and friends).

So I see nothing wrong in chasing supplements at the same time as calling for progress for cures for ageing - they are not mutually exclusive.

Posted by Reason at 11:38 AM
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This current US election cycle has had one positive consequence: CafePress has started to carry buttons and magnets as a part of its election promotions. This means that you can now buy these smaller Fight Aging! items individually or in lots of ten from the Longevity Meme store. All proceeds are donated to the Methuselah Foundation.

These make ideal gifts for friends who might be interested in healthy life extension, or as handouts if you are planning to go anywhere near a conference in the near future (such as, say, TransVision 2004).

Posted by Reason at 2:19 AM
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The Alcor Life Extension Foundation is one of the few cryonics service providers in the world. For an explanation of cryonics and its importance to the healthy life extension community, you might want to see my Longevity Meme page on the topic:

Cryonics is the only option for life extension open to many older and seriously ill people: those who cannot wait for the promised therapies of the next few decades. It is the science of placing humans and animals into a low-temperature, biologically unchanging state immediately after clinical death, with the expectation that advances in medical technology may eventually enable full restoration to life and health. A small industry of cryonics providers exists to freeze your body on death, in the hopes that future scientists (most likely using nanotechnology and nanomedicine) will be able to revive and repair you.

With the increasing level of public and government interest in cryonics over the past few years, the cryonics community has found it necessary to put far greater emphasis on debunking persistent myths, rumors and other nonsense. Alcor have taken it upon themselves to do this via their website, which has been growing and improving with time:

Myths and misconceptions about cryonics have become widespread, largely because of sensationalized news stories. Although the process is still speculative, there are powerful rational and scientific justifications for it. We invite you to explore this site and reach your own conclusions.

Some good starting points are:

• What is Cryonics?
• Cryonics Myths
• Frequently Asked Questions

I think that the first of those pages provides an excellent quick summary of the case for cryonics:

Cryonics is justified by three facts that are not well known:

1) Life can be stopped and restarted if its basic structure is preserved.

Human embryos are routinely preserved for years at temperatures that completely stop the chemistry of life. Adult humans have survived cooling to temperatures that stop the heart, brain, and all other organs from functioning for up to an hour. These and many other lessons of biology teach us that life is a particular structure of matter. Life can be stopped and restarted if cell structure and chemistry are preserved sufficiently well.

2) Vitrification (not freezing) can preserve biological structure very well.

Adding high concentrations of chemicals called cryoprotectants to cells permits tissue to be cooled to very low temperatures with little or no ice formation. The state of no ice formation at temperatures below -120°C is called vitrification. It is now theoretically possible to vitrify organs as large as the human brain, achieving excellent structural preservation without freezing.

3) Methods for repairing structure at the molecular level can now be foreseen.

The emerging science of nanotechnology will eventually lead to devices capable of extensive tissue repair and regeneration, including repair of individual cells one molecule at a time. This future nanomedicine could theoretically recover any preserved person in which the basic brain structures encoding memory and personality remain intact.

So...

• If survival of structure means survival of the person;
• If cold can preserve essential structure with sufficient fidelity;
• If foreseeable technology can repair injuries of the preservation process;

Then cryonics should work, even though it cannot be demonstrated to work today. That is the scientific justification for cryonics. It is a justification that grows stronger with every new advance in preservation technology.

As a final note, cryonic suspension is affordable. It costs no more than most major medical procedures, and can be paid for using a life insurance policy - a low monthly payment for most people. I view cryonics itself as an insurance policy; insurance against accident, age or other misfortune that would prevent a person from using the anti-aging science of tomorrow.

Posted by Reason at 5:34 PM
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I'm going to point your attention to this item at the Longevity Meme today:

The Methuselah Foundation has raised over $400,000 in pledges and donations in under a year through The Three Hundred Initiative and the generosity of early donors. These funds grow the Methuselah Mouse Prize that is building public support and encourage competition in serious anti-aging research. These are vital steps on the road to much longer, much healthier human lives. The formal launch of the Reversal Prize is in November 2004, and we need your help to reach the magic $500,000 mark in pledges by that time. All it will take is a few more people to join The Three Hundred. This is an amazing opportunity - for just a few dollars a day, you can help to defeat aging in your lifetime!

I'll add that one of the Methuselah Foundation volunteers, Thor Christensen, is offering to donate an additional $500 to the Methuselah Mouse prize fund when the next person joins The Three Hundred. In addition, new members will get Methuselah Mouse gear from me as a part of the current promotion for donors.

There are good things in the pipeline for the rest of the year, and we'd all like to make the November Reversal Prize launch something special by being able to announce that we have reached the half million mark in pledges by that time. So strike a blow for serious anti-aging research and join The Three Hundred!

Posted by Reason at 6:21 PM
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An interesting discussion on the structure of the Methuselah Mouse Prize for anti-aging research is being held over at the Immortality Institute forums:

Which Prize Structure Would You Rather See Promoted?

Only Postponement Prize - Embryonic Genetic Interventions (Same Intervention Cannot be Performed in Humans)

Only Reversal Prize - Adult Animal Genetic Interventions (Same Intervention Can be Performed in Humans)

Both Prizes

For those of you unfamiliar with the work of the Methuselah Foundation:

The Methuselah Mouse Prize is the premier effort of the Methuselah Foundation. It is a contest designed to accelerate progress towards real longevity-enhancing medicine, promote public interest and involvement in research on healthy life extension, and encourage more such research by providing a financial incentive to researchers.

The fastest way to do this, in the opinion of the prize founders, is to provide financial incentives for anti-aging research in mice. There are in fact two different prizes, Postponement and Reversal:

The goal of capturing the public imagination is best achieved by a very simple prize structure, in which money is awarded simply to the producer of the world's oldest ever mouse. This should be restricted to the species used in virtually all laboratory work, Mus musculus, but no other restrictions should be placed on the way in which the mouse's lifespan is extended, except for ones that fail to maintain its cognitive and/or physical well-being. This is analogous to the situation with boxing, for example: the heavyweight championship is the one that gets by far the most publicity and money.

A major shortcoming of this simple structure exists, however. Our main purpose is to find interventions which are effective when initiated at a late age; it is very likely that interventions that are applied throughout life will always be ahead of those initiated late. Hence, there are two prizes:

- a "Postponement Prize" (PP) for the oldest-ever Mus musculus;
- a "Reversal Prize" (RP) for the best-ever late-onset intervention.

Donors are given the option of contributing to either prize, and to date most have voted for the Reversal Prize. This is a fairly straightforward and obvious choice: we want to see therapies that can be used to extend the healthy human life span in people who are already old. Ideally, this would mean rejuvenation - some way of reversing the degenerative aging process.

Those of us who keep tabs on the progress of aging and real anti-aging research expect - even in the best case - to be waiting for decades for any effective therapies that can reverse the aging process. (Although regenerative medicine and cancer research hold out the hope of more quickly developed therapies that can repair the worst age-related damage). Anti-aging therapies that can only benefit the young are not going to be much use to us.

So all that said, some folks at the Immortality Institute would like to see a more narrowly focused prize; dropping the Postponement category, for example, or being more specific about the types of intervention that can win. Some earlier back and forth over research conditions can be found in another thread in the same forum. Both conversations are worth reading.

Posted by Reason at 5:13 PM
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I chanced across a rather depressing survey on attitudes and knowledge of serious anti-aging research yesterday:

The following information results from a poll conducted on a local (U.S.) information web site between January 2003 and February 2004. 465 people responded.

The poll showed that the majority of people (69 %) think that there will never be any meaningful treatment of the root cause of aging or that such treatments are only a very distant possibility. Most people are unaware of evidence that aging might be very treatable in the relatively short term and believe in a variety of (mostly) scientifically unpopular theories regarding the cause of aging. These attitudes have predictable results regarding the popularity of publicly funded anti-aging research.

This is one of the brick walls that we advocates are banging our heads against. Public support for anti-aging research is absolutely necessary, yet such support requires educational efforts that demonstrate real anti-aging medicine to be possible.

This survey is connected to an online book entitled "The Evolution of Aging: How Darwin's Dilemma is Affecting Your Chance for a Longer and Healthier Life" by a fellow named Theodore C. Goldsmith. The name doesn't ring any bells, but he does claim that Joao Magalhaes - who I do know and who generously contributed an article to the Longevity Meme - has commented on the manuscript. So I'll give him the benefit of the doubt while I peruse the book...so much to read and so little time to do it in.

The book keynote:

Is aging, as most people think, a fundamental, totally unalterable fact of life? Or, is aging actually like a universal, but potentially highly treatable, genetic disease? Darwin’s dilemma, a little known quirk of the theory of evolution has for more than 140 years led researchers toward considering aging as inescapable, but recent discoveries and new theoretical work indicate that major medical intervention in the aging process may in fact be possible in the relatively near future.

The author takes us on a fascinating tour of the evolution of aging theories from Darwin to the present and includes descriptions of the applicable discoveries and the politics of anti-aging research.

Take a look and see what you think.

Posted by Reason at 2:51 AM
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Rainbough Phillips at Catallarchy quotes some of Aubrey de Grey's writings on radical life extension, commenting:

I do not know if I would like to live forever, however, I suspect I will have an answer to that question after my first thousand years. Hopefully the answer will be: Why not?

There is a discussion in the comments to this post as to whether death is a good thing. Sadly, I think I am becoming inured to the ridiculous nature of these sorts of propositions: "mass death and shorter life spans are a wonderful thing: discuss." I am no longer rendered aghast at the way in which people of all stripes try to justify allowing the ongoing death toll to continue unabated. I see it all the time, and I'm all too aware that we need to step up our efforts at education and advocacy for healthy life extension and serious anti-aging research.

At least one comment reflects some of my views on the subject:

Doesn’t matter a damn how good or bad it is for "scientific progress". Ending death from old age is good regardless, and society will just have to adjust.

Pro-death people should all go commit suicide, so as to demonstrate the sincerity of their views.

I think that we should all now go and read The Fable of the Dragon-Tyrant by philosopher Nick Bostrom. Death and aging are truly monsters, and we become monsters ourselves by accepting and defending these conditions rather than fighting to end them.

Posted by Reason at 3:20 PM
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Another sign that the political side of stem cell research is heating up: another active advocacy group specifically formed to attempt to ensure that pro-research politicians are elected:

Millions of people who live with life-threatening conditions look to embryonic stem cell research as their greatest hope for a cure, but this research has been sharply curtailed and could be halted.

CASCR supports those candidates for federal office who believe in the freedom to conduct this potentially lifesaving research. We accomplish this through the use of independent expenditures to let you know where the canidates stand.

The chances are good that a member of your family, a good friend or even you may be faced with a disease or injury that is fatal or progressively debilitating. The only cure may be a stem cell transplant. But, you may not have that option. If the policy set in place by President George W. Bush, preventing the production of new embryonic stem cell lines, remains the law, such research will continue to be severely limited and could be halted in the US.

Scientists believe that embryonic stem cell therapy is the best potential treatment for many currently incurable diseases, such as cancer; degenerative neurological disorders like Parkinson’s, Muscular Dystrophy and Multiple Sclerosis; autoimmune diseases like Type 1 Diabetes and Lupus; and Sickle Cell Anemia, as well as spinal cord injury and organ regeneration. The procedure, know as somatic cell nuclear transfer (SCNT), inserts the patient’s own DNA into a donor egg in order to create stem cells which could potentially eliminate rejection as an issue in many circumstances. The magic of these cells is that they can be stimulated to develop into any type of cell in the body.

The Committee for the Advancement of Stem Cell Research is a 527 political committee organization that will run independent political advertising on this issue during the current election. This website is designed to help the concerned voter make an informed choice on the issue by education and endorsements of candidates for federal office.

CASCR seems to be a more political version of the Coalition for the Advancement of Medical Research, and is much more likely to be the product of a lobbyist group - who may or may not be primarily interested in stem cell medicine - rather than a true grassroots organization.

All this money going to lobbying could be much more productively spent in a society with a smaller, less intrusive, less regulatory government. So much is wasted because this present winner-takes-all system allows the politicians to exercise enormous control over what should be private decisions and contracts. We wind up with competing gangs of looters fighting over the spoils. You could cure a disease with the money spent on power struggles during a US election cycle...

Posted by Reason at 12:18 PM
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The new book on bootstrapping our way to radical life extension by Ray Kurzweil and Terry Grossman now has an entry at Amazon for those of you who feel like pre-ordering it.

Ray Kurzweil, Ph.D., is one of the world's leading entrepreneurs, thinkers, and futurists. A recipient of the National Medal of Technology, among many other honors, he is the author of three previous books: The Age of Spiritual Machines, The 10% Solution for a Healthy Life, and The Age of Intelligent Machines.

Terry Grossman, M.D., is also a certified naturopathic doctor who has written several popular articles on natural treatments for ailments. An expert in longevity medicine, he is the author of a leading book on life extension, The Baby Boomer's Guide to Living Forever.

...

One of the most respected scientists and futurists in America teams up with an expert on human longevity, to show how we can tap today's revolution in biotechnology and nanotechnology to virtually live forever.

Startling discoveries in the areas of genomics, biotechnology, and nanotechnology are occurring every day. The rewards of this research, some of it as spectacular as what was once thought of as science fiction, are practically in our grasp. Already it is possible to analyze our individual genetic makeups and evaluate our predisposition for breast cancer or other deadly diseases on a case-by-case basis. And once we've isolated these genes, the ability to repress or enhance them through biotechnology is just around the corner. Soon, for example, it will be feasible for 10% of our red blood cells to be replaced by artificial cells, radically extending our life expectancy and enhancing our physical and even mental abilities beyond what is humanly possible today. In Fantastic Voyage, Ray Kurzweil and Terry Grossman will show us how amazingly advanced we are in our medical technology, and how incredibly far each of us can go toward living as long as we dare imagine.

With today's mind-bending array of scientific knowledge, it is possible to prevent nearly 90% of the maladies that kill us, including heart disease, cancer, diabetes, kidney disease, and liver disease. Ray Kurzweil and Terry Grossman start the reader on a fantastic journey to undreamed-of vitality with a comprehensive investigation into the cutting-edge science on diet, metabolism, genetics, toxins and detoxification, the hormones involved with aging and youth, exercise, stress reduction, and more. By following their program, which includes such simple recommendations as drinking alkaline water and taking specific nutritional supplements to enhance your immune system and slow the aging process on a cellular level, anyone will be able to immediately add years of healthy, active living to his life.

I'm hoping that the authors place far more emphasis on what we must do to attain real anti-aging medicine than on the old school health optimization techniques - based on supplements, lifestyle, and diet - that are available today. These techniques can help to optimize your natural longevity, but - with the exception of calorie restriction - nothing is proven to extend maximum life span in humans. Far too much effort is spent on tinkering with the motor oil rather than developing capabilities relating to major engine repairs...

Posted by Reason at 10:40 AM
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"The Quest for Immortality: Science at the Frontiers of Aging" by S. J. Olshansky and B. A. Carnes came out in 2001. Olshansky is one of the conservative old guard in biogerontology, in that he doesn't believe radical extension of the healthy human life span to be possible. Scientists with this and similar mindsets are (despite good work in the past) now holding up progress towards real, meaningful anti-aging medicine.

Over at the Immortality Institute, Prometheus was kind enough to review this book:

I was going through some boxes of "old" books when I came across The Quest for Immortality by S. J. Olshansky and B. A. Carnes. (2001). Since this has not been reviewed in this forum I thought I would share my views on this book with you.

For those not familiar with Olshansky, he is one of the three authors (along with Hayflick and Carnes) of the famous/infamous essay in Scientific American, No Truth to the Fountain of Youth which was co-signed by 51 researchers including Aubrey de Grey (!). This article set out to make a stand against the information in the public domain which suggested that it was possible to interfere with the aging process. Whilst it was important to do this in the context of the snake oil peddlers out there it also tended to have an effect of throwing the baby out with the bathwater since it invalidated every single possible intervention in existence which is factually untrue (if you wish to debate this point with me be my guest).

Back to the book: This is a fine book to read if you are interested in the views of two scientists who specialize in epidimiology with a very conservative view of what can be done about aging (nothing) written in an easy style and interspersed with the occasional interesting fact.

...

Olshansky received a doctorate in sociology in 1984 and his specialization is epidemiology and biostatistics. Carnes similarly specializes in biodemography. Their particular focus comes out in the book as does their lack of focus in the necessary cell biology. The book has lashings of undue pessimism and I must say I only enjoyed the first chapter: Death and Immortality: Early Views.

...

All in all a book for those who need to have the belief reinforced that real life extension is only a dream and our destiny as food for worms is carved in stone. Now I know why it was in the box with the "old" books.

Needless to say, our future as worm food is very much not set in stone! However, a future in which effective anti-aging medicine is developed soon enough to help those of us reading this now will require funding, widespread support and greater education of the public. We can't just sit on the sidelines and expect results.

Posted by Reason at 1:16 PM
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As noted in a Betterhumans article on the topic, scientists are continuing to experience contradictory results with adult stem cells. The level of plasticity - the all-important ability to transform into other cell types - is under question. Without plasticity, adult stem cells are unlikely to be useful for regenerative work, such as growing replacement organs.

Adult stem cells from the brains of mice have proven to differentiate into blood vessel cells in an experiment that could help settle controversy over their potential.

...

However, it contradicts more recent findings that adult stem cells don't form new cells, but instead fuse with existing cells, forming a hybrid that takes on the pre-existing cell's function.

As is usual when research results appear to contradict one another, it seems that there are other mechanisms at work. Different populations of adult stem cells in the body may have different levels of plasticity. Furthermore, positive results seen to date in trials may or may not reflect on the utility of a given type of stem cell. In the long run, scientists will figure out how to make any cell perform any needed task as a part of future regenerative medicine - but the long run isn't good enough for people who are aging, suffering and dying now.

Sadly, political restrictions on stem cell research and therapeutic cloning in the US don't appear to be going away this year. An enormous amount of effort has been put into fighting or bypassing politicians on this issue, and justified effort it is too. However, elections will always be more important than lives to a certain set.

Still, as recent Senate hearings intended to hype adult stem cell research (as a way of building support for a ban on embryonic stem cell research) show, anti-research politicians and their proposed policies are now experiencing a lot more opposition. You can help!

• Help to Support Stem Cell Research and Therapeutic Cloning

In addition to writing to your elected representatives, you can further the cause of regenerative medicine by joining and supporting a number of active groups:

• Coalition for the Advancement of Medical Research
• Stem Cell Action
• The California Stem Cell Research and Cures Initiative (Proposition 71)

Posted by Reason at 7:56 PM
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A number of popular books on the topic of healthy life extension and related issues have come out in the past few years, both for and against extending healthy human life span. More are due out soon as there is increasing public interest in this important topic. Here is a brief reading list top get you started:

• The Fight Over the Future : A Collection of SAGE Crossroads Debates That Examine the Implications of Aging-Related Research
• Rapture: How Biotech Became the New Religion
• The Immortal Cell: One Scientist's Quest to Solve the Mystery of Human Aging
• Ageless Quest: One Scientist's Search for Genes That Prolong Youth
• Merchants of Immortality: Chasing the Dream of Human Life Extension
• The Fountain of Youth: Cultural, Scientific, and Ethical Perspectives on a Biomedical Goal

Don't forget to catch the Immortality Institute book of essays when it comes out later in the year:

• The Scientific Conquest of Death: Essays on Infinite Life Spans

Ray Kurzweil also has a book on radical life extension coming out later this year.

Posted by Reason at 7:13 PM
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The latest Annals of the New York Academy of Sciences is edited by biogerontologist Aubrey de Grey and entitled "Strategies for Engineered Negligible Senescence: Why Genuine Control of Aging May Be Foreseeable." The table of contents:

• Part I. The Nervous System
• Part II. The Cardiovascular System
• Part III. The Immune System
• Part IV. Cancer
• Part V. Protein Damage
• Part VI. DNA Damage
• Part VII. Hormones and Signaling
• Part VIII. Oxidative Stress
• Part IX. Nutrition
• Part X. Exercise
• Part XI. Exceptional Longevity
• Part XII. Ethical and Sociological Issues
• Part XIII. Other Topics

It's great to see Aubrey de Grey's vision for serious anti-aging research getting ever more support in the scientific community. You can read the many abstracts at the Annals website, but full texts are pay only. There's some good stuff in there:

The arguments against life extension are examined and found wanting. The consequences of life extension are explored and found challenging but not sufficiently daunting to warrant regulation or control. In short, there is no doubt that immortality would be a mixed blessing, but we should be slow to reject cures for terrible diseases that may be an inextricable part of life-extending procedures even if the price we have to pay for those cures is increasing life expectancy and even creating immortals.

...

Aging is unpopular with the general public—but, it would seem, only up to a point. Treatments that claim (sometimes justifiably) to extend the total and/or healthy life span of elderly people, or even just make them look younger, are welcomed with open wallets throughout the world. If, however, one suggests to the typical nonbiologist—or even to the typical nongerontologist biologist—that we should therefore aim, in due course, to take this desire to its logical conclusion and bring aging under the same degree of control that we currently have over most infectious diseases, one is nearly always met with strong and sometimes strident opposition. I argue here that the prevalence of this outright irrationality is largely the fault of gerontologists themselves.

...

Following a highly stimulating series of talks on the social and ethical implications of greatly extended life spans, a discussion of the issues was held, in which a series of straw polls was conducted. An alarming conclusion from these polls was that most participants thought it either probable or "not improbable" that comprehensive functional rejuvenation of middle-aged mice would be possible within 10-20 years, but also felt that biogerontologists should not yet discuss timescales (either for mouse rejuvenation or similar progress in humans) in society at large. This combination of views may be very dangerous, as it assumes that humanity will need little forward planning to transition smoothly from its current almost universal fatalism concerning the defeat of aging to a widespread appreciation of its foreseeability or even imminence.

If you want to see how scientists are talking about healthy life extension amongst themselves (both the nuts and bolts and more bioethics-like considerations), this is a good place to look.

Posted by Reason at 11:56 AM
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The Merchant of Venus at Blogspot recommends "Merchants of Immortality" by Stephen Hall:

Merchants' turned out to be a sober and somewhat sobering history of the field of "regenerative medicine", ably and earnestly undertaken by a professional journalist of science.

Hall's history neatly sums up the major issues, both scientific and ethical: fetal tissue research, telomeres, embryonic and adult stem cells, animal and human cloning, and of course, the possible social effects of a radically extended life expectancy. At the same time, he introduces you to the major players--the entrepeneurs, biologists, medical researchers, politicians and philosophers whose names you'll see almost every day in the news lately, if you're paying attention.

This book answered a lot of questions I had about the bioethics of stem cell research and has definitely helped shape my politics regarding the question. However, it may be a higher compliment to say that Merchants' has re-shaped several of my personal interests. First, I have to say that my enthusiasm for telomere applications has been largely muted (I'm afraid I was a victim of the late-90's Geron hype here), but on the other hand, I was thoroughly intrigued by what I read about nuclear transfer cloning and stem cell research, and I'll be following these topics closely in the future.

I second the recommendation. If you want to see where scientists and the wider biomedical community are on the road to developing a cure for aging, this book is a good start.

Glenn Reynolds is currently reading a more recent book entitled "The Fountain of Youth: Cultural, Scientific, and Ethical Perspectives on a Biomedical Goal", a collection of essays from both pro- and anti-life extension camps.

It's a collection of very interesting essays on the topic of longevity, from a wide variety of perspectives (both Aubrey de Grey and Leon Kass are represented, which says it all).

There are a range of books on this topic that are worth looking at (and I mentioned a few in the Longevity Meme newsletter a little while back), with more coming out this year it seems. I'm all for that: the more the merrier.

Posted by Reason at 12:09 PM
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The webcast for the Ray Kurzweil talk on NPR is now up at On Point:

Immortality is just around the corner, says technologist Ray Kurzweil. All you need to do to achieve it is hang on until the wonder of life-extending technologies such as self-repairing nanobots and therapeutic-cloning take hold.

With any luck, Kurzweil says, it may be just a matter of decades, not centuries, before the human lifespan becomes infinite -- not 100 but 200 years long.

Tune in to hear techologist Ray Kurzweil talk about his how-to-achieve the 200-year human lifespan guide.

The copywriters apparently have a fairly loose grasp on the concept of infinity, but no matter. Get thee hence and listen to the discussion! The webcast is available in Windows, Real and Quicktime streams.

Posted by Reason at 7:51 PM
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Ray Kurzweil will be speaking on the topic of radical life extension on NPR tomorrow:

Futurist Ray Kurzweil joins NPR "On Point" host Tom Ashbrook for a live discussion of radical life extension, Monday, July 12th, 8-9 p.m. EST.

On "How to Live Long Enough to Live Forever," Kurzweil discusses how to dramatically slow down the aging process, even stop and reverse it, and the social and cultural ramifications. He also describes his forthcoming book, "Fantastic Voyage: Live Long Enough to Live Forever," co-authored with Terry Grossman, M.D.

"The book makes the scientific case that immortality is within our grasp," says Kurzweil. "Our health program enables people to slow aging and disease processes to such a degree that we can remain in good health and spirits until the more radical life-extending and life-enhancing technologies, now in the research and testing pipeline, become available.

As an aside, Terry Grossman is also a cryonics supporter: you can read his two part article on the subject at the Longevity Meme.

Living long enough "to live forever" is the same concept described by Aubrey de Grey as "acturial escape velocity." If advances in medical science make it possible to live for, say, 20 extra years in good health, then that gives us 20 more years in which to research ways to extend the healthy human life span even further. We can in principle bootstrap our way to a cure for aging, one therapy at a time - if we put enough time and resources into the problem at this early, crucial juncture.

It is by no means certain that the right technologies will be developed, or that enough funding will be available to develop real anti-aging medicine in time. That is why activism and education are vitally important. There is a medical revolution in waiting, and scientists can clearly see a path to radical life extension, but medical revolutions don't happen without public support. So step up and do your part to help make longer, healthier lives a reality!

Posted by Reason at 11:16 AM
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Recall my recent post on this year's summer offensive on the anti-aging marketplace by mainstream gerontologists? I thought it would be interesting to take a look at how one of the more vocal - and comparatively responsible - groups in the marketplace is responding. The American Academy of Anti-Aging Medicine (A4M) puts out pithy press releases when attacked:

Just GROW OLD and DIE: Pay No Attention to 20,000 Physicians and Scientists Who Say Otherwise,” Suggest Gerontology Academicians

...

Count Maurice Maeterlink (1862-1949), Belgian writer, poet, essayist, and Nobel Laureate wrote that "At every crossroads on the path that leads to the future, tradition has placed 10,000 men to guard the past."

A4M has a good official position:

The A4M is a non-profit medical society dedicated to the advancement of technology to detect, prevent, and treat aging related disease and to promote research into methods to retard and optimize the human aging process. A4M believes that the disabilities associated with normal aging are caused by physiological dysfunction which in many cases are ameliorable to medical treatment, such that the human lifespan can be increased, and the quality of one's life improved as one grows chronologically older.

This comes back to one of the points I make at the Longevity Meme, which is that this battle between gerontology and the marketplace has a lot to do with confusion over terms, legitimacy and rebranding. The A4M definition of "anti-aging medicine" means something quite different from the gerontology definition - treating age-related conditions is not the same as intervening in the aging process. There is nothing (aside, maybe, from calorie restriction) that can intervene in the aging process, but there are plenty of ways to treat age-related conditions.

I would be the first to admit that I have my issues with A4M - such as their focus on old school technologies, and the fact that they allow the modern equivelant of pill and potion merchants to exhibit at their conferences. Although these folks do pay the bills so that reputable scientists can speak in the scientific portions of these events, I think A4M could certainly be putting much more effort into ensuring that the worst, borderline fraudulent and outright fraudulent offenders in the anti-aging marketplace are not allowed in.

A4M, in my opinion, is currently hurting the advance of serious anti-aging research as much as it is helping it. (I'll happily say the same and worse about mainstream gerontology organizations - they are as much a roadblock as they are responsible enablers of research). Fortunately, A4M shows signs of shaping up and becoming a much more positive influence overall; we shall see how that goes.

Posted by Reason at 1:45 PM
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Is aging a medical condition? I think I can safely assume that much of the audience here fall into the "yes it is, and let's get on with curing it already" demographic. However, a large segment of the scientific and medical community don't agree with us - some of the important points of this debate are put forward in a SAGE Crossroads debate from earlier this year:

Today’s debate is going to focus on whether aging is a disease, and what difference that makes—whether it is classified as a disease or not.

The focus, as might be expected at this venue, is on the politics of public funding. If something is not defined as a disease (or a medical condition) then it won't be eligable for government funding. Regulation based on these same definitions also hampers private efforts.

Randall Parker weighs in on this issue with post at FuturePundit that demolishes a recent (and rather weak) claim that aging is not a medical condition:

A UC Irvine scientist claims aging is not a medical condition.

I disagree! So do many others. Aging is a medical condition because an aged body does not function properly. A body that does not function properly has a disease. A disease is a medical condition.

Is gene damage a medical condition? More generally, is brain damage a medical condition? Yes, of course. If you have something in your body that is damaged then you have a medical condition.

I am amazed to see scientists promoting a naturalistic fallacy that if some process is natural it must be normal and must not be treated. Imagine making that argument about, say, a troubled pregnancy: "Sorry maam, we can't intervene to save you or your baby from preeclampsia because in our view your illness is a natural result of an interaction between your genes and your environment." Or imagine saying this about a bacterial infection: "We can't give your daughter an antibiotic to kill the Group A streptococcal infections that is causing scarlet fever because infections are natural and have been happening for all of human history. So she'll just have to die since there is no medical condition here." You'd be thought either crazy or incredibly unethical if you said such things. But today too many scientists, doctors, and members of the public at large think of aging as an inevitability to be embraced as part of the natural order. Well, aging is not inevitable. It is one big medical condition that we need to cure. Aging reversal will some day become possible and we ought to be trying much harder to make that day come as soon as possible.

Exactly, although I usually use anthrax or smallpox as an example. It's perfectly natural to die from either, but I don't see people rushing to defend them. We can already evisage the technological capabilities required to cure aging, and we should be working hard to make them a reality.

Posted by Reason at 2:26 AM
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You may recall the recent claims regarding a new aging gene named BubR1:

Researchers have discovered another regulatory gene (named BubR1) involved in the aging process. "Mutant mice with low amounts of BubR1 protein live five times shorter than normal mice. They also develop a variety of age-related disorders at a very young age. This prompted us to investigate whether BubR1 protein levels go down as normal mice age naturally -- which is indeed what we found ... we believe it is the decline of this protein with time that may trigger some of the physiological effects of ageing."

Michael Rae sent me an e-mail (with references) to comment on this item. Scroll down for the plain English conclusions if you are not following the science.

Wait... wait ... haven't I heard this one before?

"Here we show that [homozygous knock-in mice that express a [defective] ... mtDNA polymerase develop an mtDNA mutator phenotype with a threefold to fivefold increase in the levels of point mutations, as well as increased amounts of deleted mtDNA. This increase in somatic mtDNA mutations is associated with reduced lifespan and premature onset of ageing-related phenotypes such as weight loss, reduced subcutaneous fat, alopecia (hair loss), kyphosis (curvature of the spine), osteoporosis, anaemia, reduced fertility and heart enlargement. Our results thus provide a causative link between mtDNA mutations and ageing phenotypes in mammals." (1)

"A defect in klotho gene expression in the mouse results in a syndrome that resembles human ageing, including a short lifespan, infertility, arteriosclerosis, skin atrophy, osteoporosis and emphysema. ...The klotho gene product may function as part of a signalling pathway that regulates ageing in vivo and morbidity in age-related diseases." (2)

"Absence of Ku80 results in increased sensitivity to ionizing radiation, defective lymphocyte development, early onset of an age-related phenotype, and premature replicative senescence...." (3)

" The senescence-accelerated mouse (SAM) has been under development by our research team at Kyoto University since 1970 through selective inbreeding of the AKR/J strain ... At present, there are 12 lines of SAM ... Data from survival curves, the Gompertzian function and the grading score of senescence, together with growth patterns of body weight of these SAMP and SAMR mice revealed that the characteristic feature of aging common to all SAMP mice is "accelerated senescence": early onset and irreversible advance of senescence manifested by several signs and gross lesions such as the loss of normal behavior, various skin lesions, increased lordokyphosis, etc., after a period of normal development. Routine postmortem examinations and the pathobiological features revealed by systematically designed studies have shown several pathologic phenotypes, which are often characteristic enough to differentiate among the various SAM strains: senile amyloidosis ... secondary amyloidosis ... immunoblastic lymphoma ... histiocytic sarcoma ... ovarian cysts ... impaired immune response ... hyperinflation of the lungs ... hearing impairment ... degenerative temporomandibular joint disease ... senile osteoporosis ... deficits in learning and memory ... cataracts ... and brain atrophy ... These are all age-associated pathologies, the incidence and severity of which increase with advancing age." (4)

"Until you show me that you can postpone aging, I don't know that you've done anything," sniffs Michael R. Rose, geneticist at the University of California. "A lot of people can kill things off sooner, by screwing around with various mechanisms, but to me that's like killing mice with hammers -- it doesn't show that hammers are related to aging." (5)

1: Trifunovic A, Wredenberg A, Falkenberg M, Spelbrink JN, Rovio AT, Bruder CE, Bohlooly-Y M, Gidlof S, Oldfors A, Wibom R, Tornell J, Jacobs HT, Larsson NG. Premature ageing in mice expressing defective mitochondrial DNA polymerase. Nature. 2004 May 27;429(6990):417-23. PMID: 15164064 [PubMed - indexed for MEDLINE]

2. Nature 1997 Nov 6;390(6655):45-51 Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Kuro-o M, Matsumura Y, Aizawa H, Kawaguchi H, Suga T, Utsugi T, Ohyama Y, Kurabayashi M, Kaname T, Kume E, Iwasaki H, Iida A, Shiraki-Iida T, Nishikawa S, Nagai R, Nabeshima YI. PMID: 9363890 [PubMed - indexed for MEDLINE]

3. Mol Cell Biol 2000 Jun;20(11):3772-80 Analysis of ku80-mutant mice and cells with deficient levels of p53. Lim DS, Vogel H, Willerford DM, Sands AT, Platt KA, Hasty P. PMID: 10805721

4. Takeda T. [Senescence-accelerated mouse (SAM): with special reference to age-associated pathologies and their modulation] Nippon Eiseigaku Zasshi. 1996 Jul;51(2):569-78. Review. Japanese. PMID: 8783874 [PubMed - indexed for MEDLINE]

5. http://exn.ca/Stories/1998/05/13/66.asp

So in essence, it is far too soon to jump to conclusions regarding any relationship between the aging process and the BubR1 gene - just because it looks like accelerated aging doesn't necessarily mean it is accelerated aging. More research is needed, as always.

Posted by Reason at 12:15 AM
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A piece on evolutionary and social explanations for large increases in average human life span in the Paleolithic period is currently doing the rounds. Quoting from the Betterhumans version:

A dramatic increase in longevity that took place during the early Upper Paleolithic Period, around 30,000 BC, could explain humanity's evolutionary success.

...

"Increased longevity, expressed as number of individuals surviving to older adulthood, represents one of the ways the human life history pattern differs from other primates," say the researchers. "We believe it is a critical demographic factor in the development of human culture."

...

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.

The presence of grandmothers, for example, confers an important evolutionary advantage as they transfer knowledge and other resources to their daughters and their daughters' offspring.

An increase in the number of relatively old people therefore likely gave modern humans a competitive edge that ensured their evolutionary success.

Of course, "older" in this context means making it to 30. Romanticized notions of prehistory obscure the fact that life back then was nasty, brutish and short. Randall Parker has comments - serious and otherwise - at FuturePundit:

Here is my FuturePundit speculation on this report: the lengthening of lifespans created a selective pressure for higher intelligence. When people started living longer they accumulated more knowledge. The increase in available knowledge increased the value having a high cognitive ability to sort through, analyze, and apply that knowledge. A smarter person can notice more and learn more useful lessons from an accumulation of life experiences than can a less intelligent person. So genetic mutations that lengthened lifespans may have led to selection for mutations that increased intelligence. Then the selection for higher intelligence likely increased the value of living longer still more which would have fed back into selecting for longer lifespans.

But important questions remain unanswered: Did any Upper Paleolithic civilizations collapse from spiralling taxes enacted in a futile attempt to meet unfunded pension liabilities? Were massive human migrations across the continents driven by a desire to escape from old age pension taxes?

The important point to take away from this is that the presence of more relatively older, wiser people enables a more successful society to emerge. This was true back then, and it is still true today - one more reason for us to strive to extend the healthy human life span.

Posted by Reason at 10:55 AM
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In the wake of some of Leonard Hayflick's comments relating to the current "summer offensive on anti-aging medicine" by the mainstream gerontology community, a few people on the CryoNet mailing list had harsh things to say. Despite his position and history in aging research, Leonard Hayflick has views on healthy life extension that are quite close to those of Leon Kass - in other words, he is opposed to the idea of extending the healthy human life span. To quote a post from Aubrey de Grey:

First, David is quite right that Hayflick (whom I know well) thinks it would be a bad idea to cure aging. However, Hayflick and Kass are not in a minority here -- as we all know, this is the general view, and more to the point, I can report that it is the general view among biologists. Among biogerontologists the situation is different -- there is a general agreement that aging is a bad thing, and Hayflick and Holliday are in a minority -- but to call Hayflick or Holliday biogerontologists is rather a stretch since they have not been active in the lab for over a decade.

He goes on to make a few more points:

Most importantly, Hayflick and Kass matter far less than they may seem to in this. The reason they don't matter is that none of the scientific community pay them the faintest attention, and ultimately it's what the scientists feel is possible and desirable that determines what progress is made. So, the people who really matter in this are those who not only agree with Hayflick about what is possible but also have the ear of the biogerontology community -- especially if they very clearly disagree with Hayflick about the desirability. An authoritative voice that says "it would be brilliant to cure aging, yes, but we can't, not for many many decades, whatever you may hear from dangerous ignorami like Aubrey de Grey" is a far, far greater barrier to progress than any high-profile comments by people with no current authority in the field. Worse, such people don't say this in print -- only in private, behind closed doors, thereby making their message all the more difficult to challenge.

This ties in with Aubrey de Grey's explanation regarding the way in which new science is forced upon the old guard in his field. The hardest part of the process is getting the opposition to engage in a public debate on the merits of your ideas.

It has to be said that I disagree on the point of how seriously we should be taking opposition to healthy life extension. We'll be kicking ourselves later if we dismiss the efforts of Kass to impose his pro-death views (and death itself) on the rest of us only to find an organized movement growing around his views. I see a future of government-imposed limits on life span and access to medicine as all too possible at the moment.

Posted by Reason at 1:50 PM
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I was pointed to another calorie restriction diary at Blogspot (you may have to refresh a few times - Blogspot is still having issues) by one of the folks at the calorie restriction society. Like April, this diarist must be small in stature - her daily intake (900 calories) is far lower than my ideal level of calorie restriction (more like 1500 calories). Here is an interesting post:

Over 3 years ago, I built my own nutritional analysis tool based on the USDA database using Access. I have data in there for every day back to January 2001. It lets you set goals, record what you ate, does reports, finds foods high in any of the nutrients. You can add new foods and enter them using recipes.

Online calorie restriction diaries provide a useful view into what it is actually like to practice this diet on a day to day basis. I'd be happy to see more of them.

Posted by Reason at 9:05 AM
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Aubrey de Grey is very much an advocate at heart, as illustrated by recent conversation in the comments section of a Mystery Achievement post expressing opposition to healthy life extension. This was in the wake of his interview at Tech Central Station, and is worth reading.

(I commented on that post here at the Longevity Meme, since I'm not fond of the Blogspot comment interface).

The conversation should continue in the comments of this newer post.

Posted by Reason at 11:58 AM
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A young lady named April is keeping a calorie restriction diary over at Blogspot. (Blogspot is having some sort of odd issue at the moment - you may have to refresh a couple of times in order to see the page). She's certainly much smaller in stature than myself, since she's comfortable with 800-1100 calories per day. Extreme calorie restriction (CR) for me is about 1500 calories per day: I can do that without being constantly hungry provided I'm eating a sensible, tailored diet. As April notes in one of her entries:

It's interesting to talk to other CR practitioners about how they have arrived at their calorie levels. It varies a lot from person to person.

Calorie restriction diaries are very useful for other folks who are looking for ideas, recipies, tips and tricks - and also to dispel many of the silly myths perpuated about CR and how it is practiced. More people should do it.

As always, you can learn more about calorie restriction and its positive effects on health and longevity at the Longevity Meme and the Calorie Restriction Society website.

Posted by Reason at 12:52 PM
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Mainstream gerontologists don't like the anti-aging marketplace - see my thoughts on anti-aging science, medicine and businesses at the Longevity Meme for some of the reasons why:

Scientists are appalled at what is going on in the anti-aging marketplace. The more reputable businesses in that marketplace are appalled by the hucksters and adventurous branding. Anti-aging is both a valuable brand and important science that all these groups are attempting to control or profit from - in many cases their aims are at odds with one another.

The war over the meaning of "anti-aging" is being fought over money and the perception of legitimacy. It is this perception of legitimacy that determines funding for scientific research and revenues for businesses. Scientists feel, quite rightly, that the noise and nonsense coming from the anti-aging marketplace is damaging the prospects for serious, scientific anti-aging research. If everyone knows that anti-aging means high-priced cream from Revlon marketed to the gullible and brand-aware, no scientist is going to get funding for a serious proposal in aging research that uses the word "anti-aging." Worse than that, people start to assume that real efforts to reverse aging must be impossible - and large scale science requires public support and understanding.

Businesses in the "anti-aging" marketplace make money from the aura of legitimacy whether or not their products perform as advertised, and so a lot of effort is expended to create and maintain this perception of legitimacy. Those businesspeople with working, accurately marketed products carry out their own fight against opportunists, frauds and "marketeers" - businesses that are damaging the market and diluting the brand. Ironically, this is much the same argument used against the more legitimate businesses by scientists.

You may recall the annual Silver Fleece Award given out by Jay Olshansky - a conservative gerontologist - to groups that he feels are perpetrating "antiaging quackery." It went to A4M this year, and they were most displeased. I have to say that while I have my issues with A4M, they are certainly not in the same ballpark as the 2003 recipients of the award. A4M supports the Methuselah Mouse Prize, and organizes conferences at which the scientific side is quite respectable, even if the exhibition floor is packed by some of the less reputable companies and products. Their definition of "anti-aging medicine" is also respectable:

Anti-ageing medicine is really nothing more than an extension of preventive health care, the next great model of health care for the new millennium. It offers a solution to alleviate some of the burden of the burgeoning ageing population. This model is based on the early detection, prevention, and reversal of ageing-related diseases.

If they would just quit advocating human growth hormone and find some way to keep the frauds and fraudulent marketing out of their conferences, I'd be more supportive.

In any case, this year the gerontologists are making more of an effort. As noted at Medical News Today, gerontological organizations are calling for better education and greater government regulation of the anti-aging industry:

Consumers must be afforded better protection against interventions falsely claiming to reverse or retard the aging process, according to an article published by legal and medical professionals in the June issue of The Gerontologist (Vol. 44, No. 3).

The team of researchers, based at Case Western Reserve University, urge professional organizations to undertake a sustained program of specific educational efforts to designed to sort out the "helpful, the harmful, the fraudulent, and the harmless antiaging practices and products."

They suggest that many anti-aging treatments can seriously harm older persons and aging baby boomers, and may divert them from more medically-proven therapies. Currently, there are many barriers to effective governmental regulation of anti-aging interventions, state authors Maxwell J. Mehlman, JD, Robert H. Binstock, PhD, Eric T. Juengst, PhD, Roselle S. Ponsaran, MA, and Peter J. Whitehouse, MD, PhD.

Support for the preparation of the article was provided by the National Institute on Aging and the National Human Genome Research Institute. The piece also continues The Gerontological Society of America's series of summer events designed to confront the hope and hype of anti-aging medicine. The subject is addressed in special sections of the June and July issues of The Journal of Gerontology: Biological Sciences, as well as a recently released edition of the Public Policy and Aging Report, put out by GSA's policy branch, the National Academy on an Aging Society.

I'm would be very pleased to see gerontological organizations making a better effort to educate the public regarding real anti-aging science - what is possible, what can be done, and what is out of the realms of possibility. Aubrey de Grey has long said that gerontologists are not making enough of an effort to speak out, and that this damages the cause of aging science. Government intervention, however? Not good. It's just never a smart idea to invite the government in to mess up your house. You'll always regret it later ... and the history of government intervention in medical research and practice is not a pretty one to begin with.

Ultimately, mainstream gerontology has to sort out its own house as well. The conservative old guard in the field are slowing down efforts to greatly extend the healthy human life span by refusing to seriously debate proposals like that advanced by Aubrey de Grey. The times are changing rapidly as new technology allows medical science to proceed ever faster. Simply campaigning against the fraudulent portion of the anti-aging industry is not good enough - far better to embrace the future of longevity research and lead by example.

Posted by Reason at 5:36 PM
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I ran across an interesting press release from the University of Rochester today. They are touting a system for massive parallel testing of compounds and genetic modifications on yeast:

Professor David Goldfarb, of the University of Rochester's Department of Biology, has recently developed high through-put screening technologies that may allow discovery of genes and compounds that increase the lifespan of fungi, protozoa, plants, and animals. This set of technologies has potential applications in medicine, agriculture and industry, and is the subject of a pending patent application.

Using genetically engineered strains of brewer's yeast, Professor Goldfarb and his colleagues have formulated various methods, materials, and lab kits that may be used to identify genes and small compounds that increase the lifespan of organisms. Previous research has shown that key genetic mechanisms that control the aging and lifespan of yeasts are reasonably well conserved in humans. Therefore, Goldfarb's technology may be able to identify genes that normally function to control lifespan in yeast, and which could have analogous effects in higher plants and animals.

This innovation might also be used to quickly screen large chemical libraries to determine their effects on longevity in brewer's yeast. The advantage of this technology is that it may allow companies to perform large-scale screening of compounds that affect aging by measuring a simple read-out, such as optical density.

As reported in the June 4, 2004 edition of the Chicago Sun Times, researchers emphasize that the benefits of anti-aging genetic technology not only have the potential to keep people alive for longer periods of time, but also may help prevent diseases of aging like cancer, diabetes, and heart disease. Technology such as Professor Goldfarb's may provide a valuable tool to efficiently gain further insight into the mysteries of aging and age-related diseases.

These sorts of innovations in parallel testing have made the advances of recent years possible in many other fields of medical research. Why not healthy life extension?

Posted by Reason at 1:23 PM
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