People Who Advocate Suffering and Death
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Recent press on healthy life extension has in turn generated the normal run of poorly thought through pro-death op-eds, repleat with all the normal errors and knee-jerk reactions. Human nature, when geared up in accept-the-inevitable mode, is a powerful force - observe the way it can turn so many to defend the painful, slow death of tens of millions every year. How is this in any way rational now, however?

We've moved beyond the era in which aging and death were absolute and inevitable. We can see a fairly clear path towards medical technology capable of repairing age-related damage and extending our healthy life spans. Organizations already exist to encourage and advocate healthy life extension research, and biotechnology is advancing at a scorching rate.

I can't imagine we're going to be seeing pro-death articles like this one for too much longer:

Life is like a story, with a beginning, a middle and an end. Take away the end and it would seem completely purposeless.

There you go - a fully fledged justification in the mind of a columnist for the torture by age-related disease and incapacity of hundreds of millions daily, decades of it leading to death. This article really outdoes itself in packing in the errors, but you can only be so ignorant for so long. For all who enjoy life and health, it is blindingly obvious that more of both is the most valuable gift you could receive. Healthy life extension is the foremost of all 21st century technologies we should strive for.

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Decline of the Aging Immune System
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An interesting review article can be found at Immunity and Aging: "Longitudinal studies are defining progressive alterations to the immune system associated with increased mortality in the very elderly. Many of these changes are exacerbated by or even caused by chronic T cell stimulation by persistent antigen ... Lifelong exposure to chronic antigenic load is the major driving force
of immunosenescence, impacting on human lifespan by reducing the number of naive antigen-non-experienced T cells, and, simultaneously, filling the immunological space [with] antigen-experienced T cells. Gradually, the T-cell population shifts to a lower ratio of [non-experienced] cells ... the repertoire of cells available to respond to antigenic challenge from previously unencountered pathogens is shrinking. ... cells from old individuals might recognize a limited set of antigens despite being plentiful in number."

Link: http://www.immunityageing.com/content/pdf/1742-4933-3-2.pdf

Medical Tourism for Gene Therapy
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Like so many other fields of modern biotechnology, gene therapy is more commercialized and progressing more rapidly outside increasingly regulated Western regions. From BusinessWeek: "In the West, this experimental branch of biomedicine suffered major setbacks following the death of one patient in a clinical trial in 1999. Other patients later came down with cancer as a result of their added genes, and the U.S. Food & Drug Administration halted a number of trials. That created an opportunity for Chinese researchers. Without the same regulatory obstacles, they were able to take ideas that originated in the U.S. but stagnated there. ... If I were making a long-term investment in biotech, and particularly in gene therapy, I would be making it in China, not here. They have figured out how to get [gene therapy] approved."

Link: http://www.businessweek.com/magazine/content/06_10/b3974104.htm

60 Minutes on Stem Cell Research
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60 Minutes recently looked at a small range of embryonic stem cell research: "These are the cells that go to make up the heart muscle cells ... They all started out as cells from embryos. With the potential to develop into any type cell. Robbins hopes to one day inject the cells, which actually beat like a heart, into someone whose heart has suffered some kind of damage. In theory, those cells would then replace the damaged part of the heart. Robbins and his team injected cells like those directly into the hearts of mice with severe cardiac disease. The researchers then tracked the cells and determined that they had stayed in the heart and that the cells were all beating in unison. After six weeks, the new heart cells had replaced the damaged ones, and heart function was restored to near normal. ... I would say that it's at least five to 10 years away before I think that we will have enough definitive data in animal studies that it will be safe to go forward with embryonic stem cells."

Link: http://www.cbsnews.com/stories/2006/02/23/60minutes/printable1341635.shtml

Freedom of Research: Absolutely Essential to Progress
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The first meeting of the World Congress for Freedom of Scientific Research took place in Rome earlier this month. Heart in the right place, but shackling freedom to the modern (increasingly socialist, increasingly bloated, unelected, anything but free) structures of "representative" democracy seems to be a losing proposition these days. When was the last time you voted on the destructive policies - or existence at all - of the FDA? You are most certainly not free when unelected, unaccountable government employees have veto rights over everything you do and own. From the declaration:

Freedom of Scientific research is required by democracy, is a basic civil and political right and is one of the main guarantors of human health and welfare.

Freedom of scientific research is part of the fabric of democratic theory because all democracies are founded upon the value of the individual, individual choice and upon the premise that one of the first and most important functions of democratic government is to preserve and promote the liberty of citizens and do no harm. That liberty includes freedom of thought and freedom of belief.

Freedom of scientific research is a basic civil and political right because it is a dimension of freedom of thought and freedom of speech.

Freedom of scientific research is one of the main guarantors of human health and welfare for three main reasons. The first is because scientific freedom has produced some of the principal discoveries that have lead to increases in healthy longevity worldwide. Secondly we have all benefited directly and indirectly from scientific discovery. We all benefit from living in a society, and, indeed, in a world in which serious scientific research is carried out which utilises the benefits of past research. We all also benefit from the knowledge that research is ongoing into diseases or conditions from which we do not currently suffer but to which we may succumb. It makes us feel more secure and gives us hope for the future, for ourselves and our descendants, and others for whom we care. Almost everyone now living, certainly everyone born in high income industrialised societies, has benefited from the fruits of past research and it is scientific research that will discover ways of combating the new dangers, which constantly arise. Finally, in the domain of human health, medical needs are seldom simply that. They are often also opportunities to go on living or to be free; free of pain, free or more free in the sense of being mobile or more mobile, more able effectively to operate in the world. Health is important not simply because we all value health and all want long and healthy lives. It is important also because poor health is confining and good health is liberating.

For these reasons, we believe it is time to reaffirm the case for freedom of scientific research.

As I said, heart in the right place, but the path to freedom is not to be found in bloated modern democracies. The path to freedom is in a strong rule of law, firm property rights, and an absolutely minimalist government that cannot interfere in the free exercise of trade, investment and the pursuit of happiness.

Freedom of research is, in essence, economic freedom, which is no different from personal freedom - the freedom to invest and work in whatever arrangements you can freely agree upon with other people. The most rapid progress occurs in free marketplaces, free for the exchange of ideas, free for association with others for mutual benefit, free for the exchange of goods. Any and all interference by centralized entities - such as governments - is inefficient and serves only to slow things down, make goods more expensive, and ensure that some research never happens at all. This is unconscionable wherever it occurs, but for medicine most of all:

"We've taken the position that the law is illegal," Dr. Day, 59, says. "This is a country in which dogs can get a hip replacement in under a week and in which humans can wait two to three years."

...

Canada remains the only industrialized country that outlaws privately financed purchases of core medical services. Prime Minister Stephen Harper and other politicians remain reluctant to openly propose sweeping changes even though costs for the national and provincial governments are exploding and some cancer patients are waiting months for diagnostic tests and treatment.

Democracy at work, right there - and this is where the US is heading at its present rate. No thanks, not for me.

But back to the World Congress: the presentations and abstracts are worth your time, for all the whole affair seems to have little to do with actual freedom and far more to do with winning control over "democratic" appointed bureaucracies and entrenched institutions.

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More Tissue Engineering Progress
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(From EurekAlert). The production of blood vessels is one major obstacle to the creation of larger engineered replacement tissue, such as organs or portions of organs. Progress is being made, however: "With heart disorders affecting individuals globally and contributing to increasing mortality rates, there has been a need to develop new treatment options. One of the specific challenges in the field of tissue engineering is to produce blood vessels within heart muscle tissue. In this study, the researchers were successful in this task. Their live models showed significant improvement in heart function, particularly in the amount of vascularization throughout the implanted sections. Further, the tissue engineered construct remained viable even after the three-week implantation period, maintaining cardiac specific function."

Link: http://www.eurekalert.org/pub_releases/2006-02/bpl-mht022406.php

Aubrey de Grey at TED2006
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As I mentioned a little while back, biomedical gerontologist and healthy life extension advocate Aubrey de Grey presented at the recent TED2006 conference. TED is very much a zero-press zone, given its central role as a form of meet, greet and networking event for movers, shakers and the wealthy. You can't keep bloggers down, however, since a increasing number of them are movers, shakers and the wealthy: Ethan Zuckerman kindly reported on de Grey's presentation in his blog for the benefit of the vast mass of humanity without a TED2006 pass:

Introducing Aubrey De Gray, Chris Anderson does something a bit unusual, making it clear that De Gray is an extremely controversial thinker, sometimes dismissed as being unscientific. He goes on to explain that DeGray believes that people could live to be a thousand years old.

De Gray slightly corrects this impression. What he wants to do is not keep frail people alive for a thousand years - he wants to restore people to "increased vitality and robustness". Humans will face the choice of ending their lives earlier, or facing a "permanently low risk of dying soon".

...

How do you make a car last for 50 years? Either you can build it like a tank, or you can take very good care of it. When cared for and repaired by enthusiasts, cars can last indefiniately. Vintage cars die because people don't care about them.

De Gray is interested in an "engineering approach". It suggests letting metabolism "lay down damage", then correcting it with a variety of techniques. He lists a set of different techiques to combat basic cellular damage, arguing that many of these techniques are "right around the corner" - in trials in mice, possibly usable in humans in 10 years. Hence, this isn't a "research" project, but a "development" project.

...

De Gray tells us "I want to get middle-aged mice to live three times as long as they otherwise would." This means a 10 year project that he's now attempting to raise funding for.

This is a presentation that long-term readers are fairly familiar with by now - hopefully the TED attendees gained a greater exposure to and appreciation of these ideas. The important part of the event for healthy life extension research was taking place behind the scenes: networking and building support amongst the philanthropic community is essential groundwork to funding research infrastructure to extend our healthy life spans. As Zuckerman perceptively points out, this is far more a matter of development than a matter of research.

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More Signs of Commercialization
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The Sun-Sentinel reports on progress in yet another variety of first-generation stem cell therapy for heart damage: "Bioheart focuses on cell therapy, in which healthy cells are injected into the heart to replace dead tissue that forms after a heart attack. Called MyoCell, the company's product is derived from immature skeletal muscle cells, called myoblasts, taken from the patient's thigh. ... Cells naturally travel from other parts of the body to help a damaged heart, but that only lasts for a few days - not enough time for sufficient healing ... The technique we developed makes this happen for a couple to three weeks, and that produces a better recovery ... The procedure is in late-stage testing in Europe [and] Bioheart could apply for commercial approval there before year's end. Testing in the United States has not progressed as far."

Link: http://www.sun-sentinel.com/business/local/sfl-zbioheart24feb24,0,3470248.story

Removing Cancerous Stem Cells
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You may recall that accumulated mutations leading to cancer within embryonic stem cell lines were identified as a potentially serious problem - if lines became unusable at a fast rate, it would greatly impede progress. The Australian reports that the problem is on the way to being solved: "scientists have overcome a hurdle in the evolution of embryonic stem cell technology by devising a means of weeding out cells that are potentially cancerous. The [research] represents a breakthrough for the technology, whose critics have used this instability to argue stem cell research be halted. ... the research team also believes the discovery may allow abnormal cells to be identified and then purged, maintaining the health of stem cell cultures."

Link: http://www.theaustralian.news.com.au/common/story_page/0,5744,18283615%255E23289,00.html

Towards Tissue Engineered Taste
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Tissue engineers are working on a surprising breadth of of research, for all that most of the press focuses on major organs. Here, EurekAlert reports on early progress towards regenerative therapies for a damaged sense of taste: researchers "have succeeded in growing mature taste receptor cells outside the body and for the first time have been able to successfully keep the cells alive for a prolonged period of time. ... aims to help people who have lost their sense of taste from radiation or diseases. Identification of factors that promote taste cell regeneration and growth may provide new avenues of treatment for these patients. Researchers also hope to gain insight into how taste cell function changes across the lifespan, from infancy and childhood through old age."

Link: http://www.eurekalert.org/pub_releases/2006-02/mcsc-ltc022306.php

Scientists' Open Letter on Aging Research
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The Scientists' Open Letter on Aging Research is now truly open to the public:

To whom it may concern,

Aging has been slowed and healthy lifespan prolonged in many disparate animal models (C. elegans, Drosophila, Ames dwarf mice, etc.). Thus, assuming there are common fundamental mechanisms, it should also be possible to slow aging in humans.

Greater knowledge about aging should bring better management of the debilitating pathologies associated with aging, such as cancer, cardiovascular disease, type II diabetes, and Alzheimer's. Therapies targeted at the fundamental mechanisms of aging will be instrumental in counteracting these age-related pathologies.

Therefore, this letter is a call to action for greater funding and research into both the underlying mechanisms of aging and methods for its postponement. Such research may yield dividends far greater than equal efforts to combat the age-related diseases themselves. As the mechanisms of aging are increasingly understood, increasingly effective interventions can be developed that will help prolong the healthy and productive lifespans of a great many people.

The letter presently has 54 signatories, including a number of respected scientists that regular readers will recognize from news and research of the past few years.

You might recognize the same hand at work here as for the Scientists' Open Letter on Cryonics, and you'd be right. Kudos to Bruce Klein and the Immortality Institute volunteers for getting this on the road - may more signatures be forthcoming as pro-healthy life extension advocacy makes further inroads.

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On Preventative Maintenance
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Back to general health for a little while: basic good health practices will make a large difference to your future. While it's pleasant to look forward to the high-tech (and not quite so high-tech) future medicine that will extend our healthy life spans, we simply can't afford to assume that the advance of science will be rapid enough or initially affordable enough to save us from the consequences of bad health practices. Why take the chance that you'll be unable to dig yourself out of a hole that you don't have to get into in the first place?

Meanwhile, evidence that physical activity may protect against cognitive loss impresses other experts on aging. A recent study that followed more than 1,700 normal seniors for six years found those who exercised the most -- at least three times a week -- were least likely to develop Alzheimer's disease. One theory, based partly on animal research, is that physical exercise may improve blood flow and oxygen delivery to the brain and increase substances that promote the growth of tissue and blood cells in the hippocampus, a region critical to memory.

...

The Religious Orders Study, which began in 1993 and includes more than 1,000 nuns, priests and brothers across the country, has found that those who engage more often in reading, puzzles and processing information have a 47 percent lower risk of Alzheimer's disease than those who do little or none.

...

A research review published in the journal Psychological Medicine found that people who have a significant "brain reserve," or intellectual base, have a much lower risk of developing dementia. "In virtually every study in which we've looked, the more education you have, the lower the prevalence of dementia in that group," said Steven DeKosky, director of the Alzheimer's Disease Research Center at the University of Pittsburgh.

Hybrid activities -- those combining a mental stimulus with some other action -- are also the subject of scientific interest. "Some of the strongest evidence is for activities that involve physical, mental and social at the same time," said Edgerly. Examples include social dancing and coaching or refereeing a team sport, she said.

A recently published study by Sweden's Karolinska Institute offers a case in point. Researchers who followed 776 normal seniors aged 75 and over for six years found that those who said they took part regularly in mental, physical or social activities had a lower risk of dementia; those who combined all three had the lowest risk. Activities that seemed to confer more protection included political and cultural involvement, attending courses, going to the theater or concerts, traveling, being engaged in charity or church activities, and playing music with others.

...

A study last month in the Annals of Internal Medicine followed 1,740 people over age 65 for six years. The participants, all of whom had normal cognitive function at the start, initially reported how often they exercised for at least 15 minutes a day -- everything from stretching and walking to cycling, weight training and aerobic exercise. Every two years, they were given tests to determine their cognitive and physical functioning, and were also asked to assess their general health.

Those who exercised the most -- at least three times a week -- had the lowest risk of Alzheimer's, 32 percent less than the others. Also, those who started out with the lowest level of exercise benefited the most. That suggests it's especially important for sedentary people to get moving, said Eric Larson, director of the Center for Health Studies at Group Health Cooperative, a nonprofit health system in Seattle.

This is all nothing new - it's yet more support for what we all know about taking care of ourselves in the long term. Human nature being what it is, however, we all have a time preference for our own length of life. Many find it easy to throw away decades of healthy life in the future through poor habits now ... but with the advance of medical technology, you could be throwing away far more than just a decade or two. Miss the boat on the first steps towards radical life extension and you miss the possibility of centuries of interesting, healthy, ever more wonderful life.

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Stem Cell Funding in Maryland
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WJZ Baltimore reports on movement towards state funding of embryonic stem cell research in Maryland: "Two House committees approved legislation Friday to provide $25 million a year in state funds for stem cell research, with a high priority given to research on cells extracted from human embryos. Approval by the House Health and Governmental Operations Committee and the Appropriations Committee was the first step in what is likely to be a protracted and contentious debate in the legislature over one of the most emotional issues of the 2006 General Assembly session." Similar battles over comparatively small scale research funding - at least compared to Proposition 71 in California - are underway in other state legislatures around the US.

Link: http://wjz.com/topstories/local_story_055153057.html

Death Before "Inequality"
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(From TechNewsWorld). Sonia Arrison catches the same dangerous views that I noticed coming from researcher Shripad Tuljapurkar: "The political viewpoint that anti-aging technologies are problematic because not everyone gets them at the same time is either blindly impatient or a thinly concealed argument in favor of death. Some individuals might conclude they are too old to benefit from the technology. If they can't live longer and healthier lives, the thinking goes, then no one else should either. That view may offend some people's sensibilities, but it does exist. It remains unclear what drives Dr. Tuljapurkar's worry that anti-aging technologies won't spread like other advances. Whatever the motive, we should be wary of irrational solutions that call on governments to limit important scientific work. Longer lives will help us generate solutions to potential longevity problems."

Link: http://www.technewsworld.com/story/49026.html

Universal Superlongevity
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Via Betterhumans, an essay on the likely future of radical life extension: "He predicts that the initial preference for radical life extending technology will be somewhere at in the 30 to 50% range. He suspects that there will be some initial opposition in the first generation from those who are unaccustomed to it. However, writes Walker, for the first generation that grows up in a world where there are superlongevitists, the preference rate will likely jump up dramatically to about 80% or more. ... Given that superlongevity is technically possible, and this is starting to look more and more the case with each passing year, Walker believes that our descendents will opt to use this technology and that it is, morally speaking, a good thing." The fight we must win is the fight to bring this future close enough to save ourselves from suffering and death by aging.

Link: http://www.betterhumans.com/blogs/george/archive/2006/02/24/4424.aspx

The New New Betterhumans
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The staff of Betterhumans, one of the largest transhumanist community and news sites, have rolled out their latest site redesign:

I'm very excited to announce the launch of the new Betterhumans. The new site marks a transition to an even more community-driven portal. Please take a look around and see the many improvements over our previous version.

I'll admit to being mildly skeptical that they could pull off the transition from news site to community back when they first started down this path - anyone who has managed resources for an online community will no doubt laugh hollowly at the idea that it's easier than putting out news. I'm pleased that the Betterhumans staff - and community - have made it work. A thriving online community is a far more effective tool for growing the pro-healthy life extension, transhumanist community than a traditionally formatted online magazine could ever be in these increasingly networked times. We need more of them as we strive to bring an appreciation of serious anti-aging research to the public.

As always, I should note that Betterhumans has supported the Methuselah Foundation and the MPrize for anti-aging research since the early days. It's very much appreciated.

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Considering Working Anti-Aging Medicine
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The Economist digests recent discussions from the scientific community: "the point at which age turns to ill health and, ultimately, death is shifting - that is, people are remaining healthier for longer. And that raises the question of how death might be postponed, and whether it might be postponed indefinitely. ... if ageing humans can be patched up for 30 years, he argues, science will have developed sufficiently to make further repairs more effective, postponing death indefinitely. ... It would thus appear that death can be postponed by various means and healthy ageing extended by others. Whether death will remain the ultimate consequence of growing old remains to be seen." It's good to see these discussions moving further into the mainstream - all very necessary in order to craft an environment in which healthy life extension research is funded.

Link: http://www.economist.com/science/displayStory.cfm?story_id=5545419

Comments on Stem Cells, Heart Regeneration
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Some commentary from one of The Scientist blogs: "The Keystone Symposium I'm at this week in Santa Fe is billed as being about two related subjects: the molecular mechanisms of cardiac disease and the molecular mechanisms of regeneration ... the use of stem cells to regenerate the heart is already the loud buzz at poster sessions, and is at least a whisper in talks whose subjects suggest they about pure molecular mechanisms. ... I want to inject a note of caution. The ongoing clinical studies essentially support not the differentiation of stem cells into beating cardiomyocytes, but a paracrine effect. ... It may not be the stem cells themselves, but some factors they secrete, or an environment they create."

Link: http://www.the-scientist.com/blog/display/23141/

Prostate From Embryonic Stem Cells
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EurekAlert reports on an impressive step forward for tissue engineering and the control of embryonic stem cells: "Melbourne scientists have grown a human prostate from embryonic stem cells. ... the discovery will allow scientists to monitor the progression of the prostate from a normal to a diseased state for the first time. ... We need to study healthy prostate tissue from 15-25 year old men to track this process. Understandably, there is a lack of access to samples from men in this age group, so to have found a way we can have an ongoing supply of prostate tissue is a significant milestone. As nearly every man will experience a problem with their prostate, we're very excited about the impact our research will have." Much of embryonic stem cell research at this time is aimed at understanding the progression of disease.

Link: http://www.eurekalert.org/pub_releases/2006-02/ra-mpc022306.php

Commenting on Metabolic Tinkering, Longevity Genes
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Over at the Gerontology Research Group mailing list, Robert Bradbury has drawn a strongly phrased line in the sand. It happens to reflect some of my feelings on research aimed at slowing the rate of aging through metabolic tinkering (such as the calorie restriction / SIR2 / SIRT1 work on this month's Scientific American cover).

The point which often goes undiscussed by the CR folks, most biogerontologists, longevity gene fans (including people such as Sinclair and Guarente who are really studying the mechanisms by which CR works), centenarian researchers, most "anti-aging" physicians, etc. is that with these approaches the animals (and people) WILL STILL AGE and WILL STILL DIE! This approach does nothing but slow down the rate of aging -- it does not stop it or reverse it.

There is in effect a massive "con game" going on along the lines of "I agree not to discuss the man behind the curtain if you will not discuss him either." This is what generates much of the resistance to [biomedical gerontologist Aubrey de Grey]'s ideas. Aubrey may have cleverly picked SENS as his acronym de guere. It doesn't piss off as many people as SEZS (Strategies for Engineered Zero Senescence) or SERS (Strategies for Engineered Reversal of Senescence) do. People are refusing to confront the idea that we can engineer a *better* human, i.e. one that does not age at all. I suspect that in large part this is probably due to the fact that most people realize that such developments upset much of the "apple cart" that is the current reality.

Which is basically the point, though I think de Grey gives a more succinct explanation for the conservatism of modern day gerontology in this respect. I recently discussed an unpleasant future in which advocates of the moderate, slow, low-yield approach to working anti-aging medicine suck the oxygen from serious attempts at real progress through Strategies for Engineered Negligible Sensescence (SENS), or other, similar approaches based on damage repair. It's not a pleasant thought, but not out of the realm of possibility.

All this is why we must continue to hammer away at promoting a better approach in the fight to defeat aging. If mainstream funding and research leads to nothing but optimization of our present longevity, nothing more than a few additional decades of healthy life, then we will all suffer and die having missed the opportunity of radical life extension. History shows us a thousand possibilities that never came to pass - we have a chance to defeat aging in our lifetimes, but it's up to us to make that happen.

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Sinclair, Guarente on Longevity Genes
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The latest Scientific American takes a good look at research into the genetics and biochemistry of calorie restriction: "Because people have sought to slow aging for tens of thousands of years without success, some may find it hard to accept that human aging might be controlled by tweaking a handful of genes. Yet we know it is possible to forestall aging in mammals with a simple dietary change: calorie restriction works. And we have shown that Sirtuin genes control many of the same molecular pathways as calorie restriction. Without actually knowing the precise, and potentially myriad, causes of aging, we have already demonstrated in a variety of life-forms that it can be delayed by manipulating a few regulators and letting them take care of the organisms' health."

Link: http://www.sciam.com/print_version.cfm?articleID=000B73EB-3380-13F6-B38083414B7F0000

Future Anti-Aging Drugs (Or Not)
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Red Herring gets into the act with a rather traditional research mindset: "Every five years for roughly the last three quarters of a century, life expectancy in industrialized countries has risen by about one year in a phenomenally regular manner ... brought about by medicines that either cure a problem or increase the length of time people can live with chronic diseases. But drugs that prevent aging itself are on the distant horizon, and with them could come dramatic social changes. ... While many scientists agree immortality through pharmacy is not yet worthy of serious debate, and many are cautious of even making hard and fast predictions about life-extending therapies, most agree they are worthy of discussion and tentative planning." I doubt that effective therapies for aging will look anything like present-day drugs. Drugs are old school; the future is stem cells and gene therapy, engineered bacteria and nanomedical robots - and more.

Link: http://www.redherring.com/Article.aspx?a=15790

Stop Damaging Yourself!
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Step one of healthy life extension as envisaged at the Longevity Meme is to stop damaging your health - cut out the obvious sources of accumulated age-related cellular damage, and stop making lifestyle choices associated with age-related disease. You certainly can't do a perfect job - in the absence of perfect information, no-one can - but a healthier, and thus longer, later life is certainly within the bounds of possibility:

It's a truism that healthy aging begins long before you hit old age. Now a large study has confirmed that and suggested a new approach for those hoping to live a long and healthy life: Aim to reach age 50 with as few risk factors for heart disease and stroke as possible.

Not smoking, maintaining a healthy weight and warding off diabetes, high blood pressure and high cholesterol may drastically reduce your risk of cardiovascular disease and add 10 years to your life, the study reports.

Basic good health is not rocket science; talk to your physician if you're unsure about any of it. Most people are well aware of the trade-offs they make in terms of present bad habits versus future health consequences - but too few realize that what looks like a 10 year reduction in life span under the healthcare available today might mean they'll miss the boat on the introduction of working anti-aging medicine. Missing the boat means possibly missing out on centuries or more of healthy life if medical science moves forward at a fast enough pace.

Why take that chance? If you like life, take care of your health and support medical research into the technologies of healthy life extension - you might just wind up seeing a whole lot more of the future than was ever deemed possible.

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NYT on Cancer Stem Cells
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The New York Times reviews the state of research into cancer stem cells: "stem cells are the source of at least some, and perhaps all, cancers. At the heart of every tumor, some researchers believe, lie a handful of aberrant stem cells that maintain the malignant tissue. ... It's a very challenging population of cells to identify, but thus far in every cancer in which cells have been carefully screened they have been found ... If the notion of cancer stem cells is correct, how can they be eliminated without also killing the normal stem cells that are vital for maintaining the body's tissues? Researchers hope that the cancer stem cells, because of their excessive activity, may be more dependent than normal cells on certain cellular processes and thus will be more vulnerable to drugs that block those processes."

Link: http://www.nytimes.com/2006/02/21/health/21canc.html?pagewanted=print

Hunting for Stem Cells in the Brain
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If, as I suspect, neurodegenerative disease is what we should be most concerned about in the longer-term future of health and medicine, then it is vital that researchers start to apply the methods of regenerative medicine to the brain as soon as possible. Unlike other body parts, the brain doesn't allow us the last resort option of tissue engineering a new organ for transplant - we are our brains, so they must be delicately, cleverly repaired in situ. Regenerative medicine based on the use of stem cells seems to offer the best bet for the near future in this regard.

Stem cell research is progressing: scientists recently learned how to produce dopamine neurons from embryonic stem cells to treat Parkinson's disease, for example. Other groups are making progress in healing the brain through the use of adult or non-embryonic (but still pluripotent) stem cells isolated from bone marrow, cord blood, teeth or elsewhere in the body. There is a great deal of groundwork yet to reach completion when it comes to understanding neural regeneration or the brain itself at a deep enough level, however. It's a big job.

For a look at some of the latest research, see this article:

A study led by a Johns Hopkins neurosurgeon has provided the first comprehensive map of a part of the adult human brain containing astrocytes, cells known to produce growth factors critical to the regeneration of damaged neural tissue and that potentially serve as brain stem cells.

...

Because the potential existence of human brain stem cells could have an enormous impact in understanding and subsequently developing treatments for brain diseases and injury, Quinones says his team set out to learn more about how new cells are formed in this critical area in the adult human brain.

...

"We do not think that ependymal cells are stem cells," he says." However, they might mutate and become cancerous. They might be communicating or relating to astrocytes. At this point, we are only scratching the surface. But if we can achieve a better understanding of why these cells are there and how they function and/or migrate, this could help us treat brain tumors such as ependynomas or even gliomas as well as help us treat neurodegenerative diseases and brain trauma"

As you can see, getting to the good stuff is exceedingly resource intensive; the brain is very complex. The payoff for isolating and understanding populations of neural stem cells is huge, however - huge and very necessary for our future health and wellbeing.

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More From the AAAS Annual Meeting
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The Senior Journal has another article on discussions of healthy life extension at the American Association for the Advancement of Science annual meeting: "While future models seem bleak to some, [there] is much to be learned from the past. It may be more difficult to adjust to abrupt fertility changes than to anticipated increases in life expectancy due to mortality change ... Thus, since the developed world has already dealt with rising and subsequent falling fertility rates, she believes the future may not be as problematic as some believe. ... Now the question is: What will the adverse consequences of living a long life be? I think they will not be anything we cannot deal with." Being alive and healthy to tackle issues is far better than being dead - I hope this is as obvious to most folk as it is to me.

Link: http://www.seniorjournal.com/NEWS/Aging/6-02-20-NeverDying.htm

Xenotransplantation Versus Diabetes
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Under competition from stem cell based regenerative medicine, work on viable xenotransplantation therapies moves forward. From EurekAlert: researchers "have successfully reversed diabetes in monkeys using transplanted islet cells from pigs. ... Researchers have already had success reversing type 1 diabetes in humans through islet transplantation, however, the demand for islet cells grossly outweighs the supply. ... a safe and reliable source of islet cells must be found. ... These results suggest it is feasible to use pig islet cells as a path to a far-reaching cure for diabetes. Now that we have identified critical pathways involved in immune recognition and rejection of pig islet transplants, we can begin working on better and safer immunosuppressant therapies with the eventual goal of bringing the treatment to people." This strategy may also be of use in treating type 2 (age-related) diabetes, but it's worth remembering that preventation is an effective alternative in this case.

Link: http://www.eurekalert.org/pub_releases/2006-02/uom-uom021606.php

Commercialization of Stem Cell Therapies Rapidly Moving Forward in India
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An Indian news article caught my eye today:

Reliance Life Sciences (RLS), the pioneer of embryonic stem cell research in the country, is likely to launch its first stem cell-based therapies for [neurodegenerative] diseases, including Parkinson's and ocular diseases and spinal cord injury soon.

Considering the successful completion of the pre-clinical and clinical studies with due regulatory approval in another six months to one year period, these novel therapies are likely to be launched in the country by the end of next year, sources from the company said.

"As far as the embryonic stem cell group is concerned, a few of them are in the pre-clinical stage and the results are quite promising. We expect that most of our research efforts into the area of stem cells and regenerative medicines, including tissue engineering and molecular diagnostics, will reach the commercial stage in a year or two," said K V Subramaniam, head, Reliance Life Sciences.

Reliance Life Sciences is a well-backed operation by the look of it; I imagine that this is the visible tip of the iceberg in terms of stem cell research in India - money to burn on PR and media strategies in addition to research. Even discounting optimism in their schedules, the projection of commercial regenerative medicine by the end of 2007 is very good news for the field. If large Indian concerns are at this point, then other similar groups around the world are certainly looking at the same sort of schedule.

India suffers under a fairly heavy hand of government, with more than its share of destructive socialist policies and corruption. It may still be the case, however, that medical research and the commercialization of new medical technologies is not as held back as it is in the US - meaning that Indian politicians haven't yet introduced anything as monumentally terrible as the present FDA. I don't see anyone rolling out cell therapies based on embryonic stem cell research in the US by the end of 2007.

As I've said before, this sort of competition from different regions - quickly leading to large-scale medical tourism from those parts of the world that fall behind - is probably the best short-term hope to slow the ongoing destruction-by-regulation of the medical research and commercialization infrastructure in the US.

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Telomere Length and Aging
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Researchers have been retiring the telomere theory of aging for a while now, but telomeres do play an important role in many processes and medical conditions. "decreasing telomere length in a number of different tissues in humans with age, have led to the suggestion that telomeres play a role in cellular aging in vivo and ultimately even in organismal aging. ... Telomere length was measured [in] blood cells from 812 persons, age 73 to 101 years ... analyses revealed that longer telomeres were associated with better survival ... This longitudinal study of the elderly and oldest old does not support the hypothesis that telomere length is a predictor for remaining lifespan once age is controlled for." This sounds like shorter telomeres are not good, but the sum of all other progressive age-related cellular damage is worse.

Link: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16477260

Calorie Restriction In Primates
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We already know that many of the beneficial effects of calorie restriction observed in short-lived mammals (such as mice) also show up in humans - which is good enough for most practitioners, who expect to see gains in life span carry across as well. Primate studies have been ongoing, and ABC News reports on one set of results: "Hansen has long studied the effects of calorie restriction in roughly 300 rhesus monkeys. Cutting calories can pay off when it comes to longevity: Monkeys fed 30 percent less over the long term extended their lifetimes to 30 years from an average of 23 years, Hansen said. The slimmer monkeys staved off the diabetes, high cholesterol, hypertension and other weight-related ailments that typically shortened the lives of their heavier peers." In fact, it's not clear that healthy life extension due to calorie restriction can be completely ascribed to less fat and lower weight - a lot more is going on under the hood.

Link: http://abcnews.go.com/Health/wireStory?id=1634128

Progeria Continues to Illuminate
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Research into the rare accelerated aging condition progeria continues to provide insight into the degenerative processes and failure modes associated with normal aging: "In children with progeria, a mutant protein accumulates in blood vessel cells, hampering their ability to grow and multiply or killing them outright. In mice that produce this same toxic protein, the effect is similar: These vascular cells become damaged or die. These are the findings of two research reports published in the Proceedings of the National Academy of Sciences. Both shed important new light on the progression of progeria, a rare and fatal genetic condition that causes accelerated aging in children. But they may also illuminate the cause of atherosclerosis in adults. Also known as hardening of the arteries, atherosclerosis is a leading cause of heart attacks and strokes."

Link: http://www.brown.edu/Administration/News_Bureau/2005-06/05-079.html

Views of the Future
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From the Kansas City Star, competing views - both within and without the scientific community - on the future of human longevity and working anti-aging medicine: "Halting the aging process completely is far beyond the current understanding of science, de Grey said. Instead, researchers should act like engineers, repairing damage to the body's cells and tissues before it progresses to disease. The techniques for doing that are within reach ... Austad dismissed de Grey's ideas as mere 'thought experiments.' Austad agreed, however, that progress in delaying aging would come in the next couple of decades. People will live to be 150, he predicted. 'I think that person is alive right now,' he said. ... Scientists may be able to apply some of the lessons learned from basic anti-aging research to develop drugs that prevent metabolic damage or that mimic the beneficial effects of restricting calories ... But those advances are more than a decade away, Michaelis said."

Link: http://www.kansascity.com/mld/kansascity/news/13902165.htm

Aubrey de Grey, Others at the AAAS Meeting
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The annual meeting of the American Association for the Advancement of Science (AAAS) is presently underway in St. Louis. One of the first panels was "The Outer Limits of Human Lifespan", featuring Aubrey de Grey, Steven Austad, Shripad Tuljapurkar (who needs a better grounding in economics) and other gerontologists and researchers. The AAAS is a weighty organization, and the meeting is well covered in the US press; a selection of excerpts of interest follows, starting with the report from the AAAS website:

De Grey is increasingly visible in the news media, and controversial among his colleagues. Many scientists believe that there are good reasons to doubt the imminent development of such therapies, and point out that there are potential drawbacks and side-effects to consider.

A panel of experts discussed the future of the human life span Friday 17 February at the 2006 AAAS Annual Meeting, and also examined the potential demographic and economic effects which such life-extension measures could have.

De Grey, a biomedical gerontologist who studies the biological and medical aspects of old age and the process of aging, believes aging may be postponed by repairing the "damage," or the cellular and molecular "side-effects" that accompany metabolism.

"My view is that it would be much easier to repair and reverse, or at least to make harmless, those molecular and cellular things that are happening with aging rather than to prevent them in the first place," he said. To that end he has developed a comprehensive plan, entitled "Strategies for Engineered Negligible Senescence" (SENS), which categorizes seven basic types of "damage" and groups each with a proposed repair method. Each type of damage becomes a target for a proposed therapy. For example, one category includes cell loss and cell atrophy, which de Grey proposes to repair or obviate by implementing stem cells, growth factors and exercise.

Fountain of youth within reach?

In animal studies over the past 15 years, scientists have found that restricting the caloric intake of animals and mutating certain genes slows the aging process and makes them live longer.

"We've been wildly successful in extending life and improving health of a variety of animals. It has made even those of us who are skeptical think it might pan out with humans," said Steven Austad

...

There is a considerable chance that, in the next two decades, anti-aging therapy could increase a middle-aged person's life by 20 years, said Aubrey de Grey, a biomedical gerontologist at the University of Cambridge in England. Likewise, between 2010 and 2030, the age of death may rise an average of 20 years if anti-aging therapies are applied.

...

Still, de Grey and anti-aging therapy has been met with stiff resistance.

De Grey told UPI that this resistance is symptomatic of a "pro-aging trance," and that Americans do not see aging for the ghastly process that it is.

"We're making ludicrous excuses for aging that we never use for heart disease," de Grey said. "But there are no reasons [against anti-aging] that can outweigh 100,000 people lost a day."

Researcher forsees 1,000-year old people:

Living indefinitely, or at least hundreds of years, is not an outrageous scientific proposition, said Cambridge University scientist Aubrey de Grey.

Achieving what he called "life-span escape velocity" by always staying a couple of decades ahead of death is theoretically possible, although probably not for another half century.

"If you could give people alive now another 30 years," de Grey said, "that gives (scientists) another 30 years to get more advances."

...

University of Texas cell biologist Steven Austad called de Grey's 1,000-year vision science fiction. However, Austad said through genetic advances and by learning how to treat health problems at the molecular and cellular levels, people today could live to 150.

How would you like an extra 25 years of life?

Aubrey de Grey, a gerontologist at the University of Cambridge, England, told the American Association for the Advancement of Science on Friday that he feels science needs to make a more coordinated push toward anti-aging medicine.

He compared his approach to restoring storm damage to a house. "This means that an individual who is already middle-aged or even older can in principle be restored . . . to a biologically more youthful state."

The researcher said he feels there's a 50 percent chance that, within the next two decades, scientists could develop a line of therapies that would give middle-aged people an extra 25 years of healthy life. "Making 80 like 60 is a reasonable goal, but extending lifespan is really only a side effect to therapies that keep people healthy and robust as they grow older."

Science forsees a brave old world:

Aging occurs as the body becomes less able to cope with the byproducts of metabolism and other chemical processes that make life possible.

Exercise becomes harder; thinking gets slower. Eyesight dims. Bones grow frail.

Halting the aging process completely is far beyond the current understanding of science, de Grey said. Instead, researchers should act like engineers, repairing damage to the body's cells and tissues before it progresses to disease.

The techniques for doing that are within reach, according to de Grey.
"The engineering process is more realistic," de Grey said. "Repairing, reversing or in some cases making harmless the damage caused by metabolism."

Given enough financial resources, scientists have a 90 percent chance of doubling the life span of laboratory mice in 10 years, de Grey said. Given 15 more years, they have a 50 percent chance of doubling the remaining life span of a 55-year-old.

As the concepts of healthy life extension are increasingly widely dispersed through the mainstream media - and other, larger segments of our cultural conversation about medical technology and aging - the barriers to large-scale funding start to fall. It is vitally important that advocates within and without the scientific community continue to push hard on the topic, as the largest obstacles blocking the path to a future of far longer, healthier lives are almost all cultural - i.e. creating an environment in which it is possible to obtain sufficient funding to enable significant progress within our lifetimes.

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Death (For Everyone) Before Inequality (For Anyone)
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There's something about the prospect of beneficial technological and medical progress that drives some people a little batty. Witness the slide off into the deep morass in this report:

In his research, Tuljapurkar selected representative populations from different countries around the world and examined relationships between historical trends in aging, population growth and economic activity. His analysis combined these data with forecasts on the future of anti-aging treatments from leading researchers in the field.

The result? "We've come up with a scenario: Starting around 2010, we could see lifespan increase dramatically," he predicted.

Tuljapurkar estimated that between 2010 and 2030, the modal, or most common, age of death will increase by 20 years if anti-aging therapies come into widespread use. This projected increase reflects a lifespan growth rate that is five times faster than the current rate, increasing the modal age of death in industrialized countries such as the United States from roughly 80 years to 100.

...

Tuljapurkar warned that the distribution of anti-aging technologies is likely to be in the hands of companies that have a history of focusing solely on profit rather than the imperative to distribute medicines to those who need them most.

"Big pharmaceutical companies have a well-established track record of being very difficult when it comes to making things available to those who can't pay for them," he said.

...

If anti-aging technologies are distributed in the unchecked free market, "it's entirely likely to me that we'll wind up with permanent global underclasses, countries that will get locked into today's mortality conditions," Tuljapurkar said. As the gap widens and rich countries continue to invest in anti-aging technologies, the developed world may become increasingly less willing to disseminate the technology to other nations, he said: "If that happens, you get negative feedback, a vicious circle. Those countries that get locked out stay locked out."

...

"What we've tended to do historically with medical advances is to take the reasonable position that we should implement everything that comes along," Tuljapurkar said. "However, we are now approaching a stage where it's necessary to look the implications before we rush in--at least so we can prepare ourselves. We need to confront the prospect of inequality head-on, instead of waiting 10 years and then saying, 'What a surprise!'"

I find it very strange that apparently intelligent people can field this sort of argument. Replace working anti-aging medicine with, say, working heart transplants, or working kidney dialysis and see how far you get in trying to convince people that suppliers in the developed world are keeping such technologies out of the hands of others, or that we must stop using medicine that is not universally available. Quite aside from the glaring failure to understand simple economics, it is deeply depressing that we live in a world in which people argue for the enforcement of large-scale, preventable suffering and death.

Life is unfair, make no mistake. People are unequal in opportunity, capacity and the hand they were dealt at birth. To think that this truth can be removed in any way, shape or form is to betray a profound ignorance of economics and the human condition. You cannot make life better at the bottom by tearing down the top; the top is where progress happens, progress that lifts the quality of life for everyone. Punishing success in order to reward failure has predictable results - more failure and less success. The wealthy of 1950 were far worse off than the poor of today precisely because progress brings economic rewards to the successful.

Arguments based on inequality are, at root, made from a misunderstanding - willful or otherwise - of the way in which wealth, medicine and technology are best created. Rapid progress for all requires a free market, strong rule of law and property rights. Such a culture necessarily has a power law distribution of ownership and success. There's a reason the US has led the world in technology, for all that it's going to the dogs nowadays - it's the flip side of the reason that communism, socialism and the politics of envy lead to poverty and suffering.

Creating "equality" by taking from the successful ruins the creation of wealth - very much a non-zero sum game - for all. It takes away the vital incentives and rewards for success. At the end of the process, as demonstrated by all that transpired in the Soviet Union, you are left with the same old inequalities, but now taking place amongst ruins, starvation and disease.

Economic ignorance is the death of cultures; it is presently eating away at the US, and is sadly most advanced in medicine and medical research. People who favor equality and envy over wealth and progress are, unfortunately, usually comparatively wealthy themselves and thus largely insulated from the short-term consequences of their ignorance. These dangerous philistines will have to decide in the years ahead whether their dearly-held positions are worth losing their lives to, not to mention the lives of everyone they manage to kill - at the rate of 100,000 with each and every day of delay on the way to working anti-aging technologies.

Fighting economic ignorance is very much a part of fighting for longer, healthier lives - because economic ignorance is the root of objections, delay and destructive regulation and governance. It's also at the root of darker paths best not taken, such as government-mandated limits to life span. We should remember that.

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Healthy Aging and Longevity Conference
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The call for abstracts has been made for the 3rd International Conference on Healthy Ageing and Longevity, to be held in Melbourne this October: "The primary aim of the conference is to promote interdisciplinary collaboration and facilitate the exchange of ideas, information and practical solutions in relation to the prevention and treatment of age-associated disease across the lifespan, the delivery of optimal care to ageing individuals, and understanding and intervening in the ageing process and determinants of longevity. ... All areas of research in health, ageing and longevity are welcomed, including social sciences, public health, basic science, clinical science, translational research, and health and social services." The first two conferences were worthwhile affairs.

Link: http://www.longevity-international.com/cms/details.asp?NewsID=159

Calorie Restriction Studies
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A Sun-Sentinal article looks at the beneficial effects of calorie restriction in humans: "The 25 subjects, who had consumed about one-third less calories than most people would normally eat for an average of 6 1/2 years, had heart walls that were more elastic, with ventricles that relaxed more readily to fill with blood ... a promising sign that a science rooted in animal data might help humans extend their life span. ... Fontana thinks reducing inflammation may be key. Inflammation usually increases with age and induces effects similar to wound healing, which makes tissues stiffer. Fontana's study found reduced blood levels of two inflammation-linked proteins ... the National Institute on Aging has initiated a clinical trial that will randomly assign either a caloric restriction diet or a normal diet to 240 people. The trial will follow people on caloric restriction for two years and examine the health benefits and risks. Recruitment is expected to start in August."

Link: http://www.sun-sentinel.com/news/local/southflorida/sfl-217foodintake,0,2865599.story

Ending the Traditional Run to Moderation
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Wealth and large-scale funding have a strong association with conservatism. This is in the dictionary definition sense, of course - an emphasis on established institutions and standards, and a preference for gradual development over abrupt change. The more weight there is to shift, the more slowly and carefully it moves.

Conservatism is really the bottom line when it comes to asking why there are no highly-funded organizations with an outright, up-front mission of research to attain radical life extension. The manifestations of this conservatism differ between funding cultures, but the source is the same. Venture funding in medical research, for example, is guided into the rut that is the FDA and the regulatory notion that aging is not a disease and therefore no therapy can be approved to treat it. If your business plan involves fighting bureaucracies in order to get your product out there, I can safely say you're not going to get very far in your search for seed capital. So for all the futurist talk behind closed doors, you will hear not a peep on healthy life extension even from those funded companies working away on technologies of great - and entirely obvious - application. To talk about extending the healthy human life span is the instant death third rail of funding in medicine.

On the other side of the fence, philanthropists look to mainstream institutions in medicine, ossified as they are, for guidance. So the situation isn't much better. Extremely wealthy philanthropists such as Larry Ellison and John Sperling take the incremental approach, whether developing a corporate ecosystem to support new technologies or supporting mainstream gerontology. With very few exceptions, this is simply the way things work.

So it is that the run to moderation is what we have traditionally seen from advocates of radical life extension who are pushing into business or funded research. Large-scale money comes with strings, and those strings are tied taut to the conservatism of the funder or funding organization. You can see this in practice in gerontology; a great many scientists agree with biomedical gerontologist and outspoken advocate Aubrey de Grey on the moral necessity of the fight to cure aging, but all too few are willing to step up and say so on the record.

This whole situation must - must! - change if we are to see great strides in extending the healthy human life span, in fighting the horrors of degenerative aging and winning, within our lifetime. I do not believe that any plan that relies on a sea change in human nature will work, however. Conservatism and wealth go hand in hand, and this will continue to be so while humans still think, feel and interact much as they do today. Rather, we advocates must work to turn what were once seen as unthinkable goals for radical life extension into the conservative, mainstream position on the future of medical research.

I have talked before about the merits of the suitable outrageous extreme as a cultural device for advancing the cause of healthy life extension. This device has been working, and working well. A few years of making a plausible scientific case for medical technologies capable of supporting healthy life spans of 1,000 years or more has already notably moved the debate. Supporters of healthy life extension in the mainstream can now openly discuss and advocate 10 and 20 year healthy life extension with no funding repercussions. We can certainly keep this process going, but progress is damaged by those who make the run to moderation, taking a vow of silence or accepting lesser research goals in return for funding. Every voice that falls silent makes it that much harder to gain support for our position.

Aubrey de Grey is absolutely right to present the fight to defeat aging as a moral cause. It is exactly that. 100,000 people lose their lives to aging each and every day - there is little any of us could do that will have more impact on the world than helping to stop this carnage. Those who advocate the defeat of aging must find the means and courage to continue to speak out in support of radical life extension even as they are reaching for the funding that will enable their work to continue and grow.

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Cord Blood, More Pluripotent Stem Cells
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(From Medical News Today). The disadvantage of therapies based on stem cell transplants (rather than the use of adult stem cells from the patient) is the need for a reliable, scalable source of cells. Some researchers are digging into cord blood, with signs of early progress, such as "a small population of cord blood cells with the characteristics of more primitive stem cells that have the potential to produce a greater variety of cell types. ... Transplantation of these human cord blood stem cells into laboratory rodents with experimental strokes resulted in significant reductions in the size of brain lesion, and improved these animals' use of their limbs. ... Some of the transplanted stem cells developed into 'neuron-like' cells that are typically found in the brain. In addition, the transplanted cells also induced an unanticipated reorganization of host nerve fibers within the brain."

Link: http://www.medicalnewstoday.com/medicalnews.php?newsid=37696

Microglia Versus Alzheimer's
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From the Canadian Institutes of Health Research, a potentially useful insight into existing defense mechanisms against Alzheimer's amyloid plaques: "Alzheimer's disease is characterized by the accumulation of amyloid proteins in the brain. These proteins form plaques around which microglia, the central nervous system's immune cells, aggregate. These microglia appear to be incapable of eliminating the plaques ... although the brain's resident microglia do appear to be poorly equipped for combating amyloid plaques, an entirely different case prevails for another type of microglia: those derived from bone marrow stem cells. ... bone marrow-derived microglia infiltrate amyloid plaques and succeed in destroying them most efficiently. These newly-recruited immune cells are specifically attracted by the amyloid proteins that are the most toxic to nerve cells."

Link: http://www.cihr-irsc.gc.ca/e/30601.html

More on Longevity Genes
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I should mention that there are any number of genetic tweaks and characteristics that cause shortened life span via something that may look a lot like accelerated degenerative aging (or some aspect of degenerative aging). Here's one example:

Aging is a highly complex biological process that is believed to involve multiple mechanisms. Mice that have small amounts of the mitotic checkpoint protein BubR1 age much faster than normal mice ... Our findings suggest that early onset of aging-associated phenotypes in mice with mitotic checkpoint gene defects is linked to cellular senescence and activation of the p53 and p16 pathways

While educational - there's no such thing as useless knowledge in biochemistry, as it will all be needed one day - this isn't really all that exciting. It doesn't demonstrate a mechanism that can extend life span. The body, or indeed any individual cell, is an enormously complex machine; a wide range of damaged, bad or missing components can cause it to grind to a halt far sooner than it otherwise might, and in ways that look very similar to the end fate of a fully functional, but old system.

With that in mind, here's a better discovery - a gene whose absence shortens life span, but is also associated with centenarians:

Perturbations in genomic stability result in cancer, a reduced life span, and premature aging. MLH1 is a mismatch repair enzyme that acts to maintain genomic stability, and a loss of MLH1 increases cancer incidence and apoptosis resistance, which suggests a link between MLH1 and longevity. We found here that MLH1 is associated with longevity by comparing a centenarian group with a control group. Our data indicate a critical role for MLH1 in longevity.

A nice demonstration that better DNA repair capabilities lead to a longer healthy life span, on average. You may be suffering age-related damage to your DNA, but your body is naturally better at repairing this damage.

Still, the same old comments apply - the demonstration is nice, but we already know a great deal about the association between DNA damage and age-related disease and degeneration. Tweaking a gene or its expression - by drugs or more advanced methods - won't get you very far in the grand scheme of things, even in the (at this time unlikely) case it does work to extend your healthy life span to match that of centenarians. So why spend time working towards that rather than working towards the capability to fix all forms of cellular damage far, far more efficiently that our present biochemistry?

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A More Promising Column
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(From the Sunday Herald). There's hope for columnists yet - for every knee-jerk pro-death and suffering reaction, I see someone who understands the prospects for the future of health and longevity, even if not necessarily wholly supportive. "Do we really want to more than double the allotted biblical span? Most would say not, but most, I'm prepared to bet, are lying. After all, the predictions of increased life expectancy do not presume incapacity. ... Age, they report, is just another disease, and curable. What about that? ... If it implies a society that prefers conservatism to creativity and the occasional rebellion the game will have been worth less than the candle. ... But if it means centenarians saying that they are too busy to fight a stupid war this week, or that they remember only too clearly where the last political rebranding led, or that they have had it up to here with fads and social trends, I might just take the pills."

Link: http://www.sundayherald.com/53991

Collagen On Demand
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Another step forward for tissue engineering appears at innovations-report: collagen "is the most important structural protein in the body ... collagen has defied the efforts of biomedical researchers who have tried mightily to synthesize it for use in applications ranging from new wound-healing technologies to alleviating arthritis. The reason: Scientists were unable to synthesize the human protein because they had no way to link the easily made short snippets of collagen into the long, fibrous molecules necessary to mimic the real thing." Now, the problem has been solved. "We can make collagen that duplicates nature exactly, but we can diverge from that when it is desirable ... Now we can make synthetic collagen that's longer than natural collagen. We just don't have to take what nature gives us. We can make it longer and stronger."

Link: http://www.innovations-report.com/html/reports/life_sciences/report-55291.html

On Centenarians
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(Via the Americal Journal of Clinical Nutrition). Thomas Perls, director of the New England Centenarian Study gives an interesting perspective in this paper: "Many people believe that the older a person gets, the sicker he or she becomes. The result can be quite a pessimistic view of very old age. If this were true, most if not all centenarians would have significant disability. However, ~90% of centenarians in a population-based study were functionally independent at the average age of 92 y. Thus, to achieve extreme old age, a much more enabling point of view emerges: the older an individual gets, the healthier he or she has been. Centenarians thus have the potential to represent a model of relative resistance to age-related diseases and slower aging." Of course, a more modern school of thought states that it'll be far more efficient and effective to jump straight to reversing aging rather than trying to slow it or cure the end results, one by one.

Link: http://www.ajcn.org/cgi/content/abstract/83/2/484S

Longevity Genes at Scientific American
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The March issue of Scientific American discusses longevity genes, and what might be done with a greater understanding of how some people resist aging so much better than others:

You can assume quite a bit about the state of a used car just from its mileage and model year. The wear and tear of heavy driving and the passage of time will have taken an inevitable toll. The same appears to be true of aging in people, but the analogy is flawed because of a crucial difference between inanimate machines and living creatures: deterioration is not inexorable in biological systems, which can respond to their environments and use their own energy to defend and repair themselves.

At one time, scientists believed aging to be not just deterioration but an active continuation of an organism's genetically programmed development. Once an individual achieved maturity, "aging genes" began to direct its progress toward the grave. This idea has been discredited, and conventional wisdom now holds that aging really is just wearing out over time because the body's normal maintenance and repair mechanisms simply wane. Evolutionary natural selection, the logic goes, has no reason to keep them working once an organism has passed its reproductive age.

While programmed aging has given way to the wear and tear viewpoint - best expressed in the reliability theory of aging - it is certainly the case that our genes determine much of the response to that wear and tear (in the form of accumulated biochemical and genetic damage in and around your cells). The reductionist view of aging clearly points to a narrow taxonomy of options for living a longer, healthier life:

  1. Reduce your exposure to events and processes that cause damage
  2. Be more resistant to the modes of damage - suffer less damage for the same level of exposure
  3. Be more resistant to developing disease and medical conditions as a result of accumulated damage - have a higher damage tolerance
  4. Repair the damage before it reaches problem levels

Your genes determine (b) and (c), and there is always the possibility that greater understanding of how and why this is the case - going all the way down to the level of biochemical processes - will lead to medical technologies that can provide the similar or greater benefits.

Sadly, anything other than (d) - in essence, the development of working anti-aging medical technology within your lifetime - will still see you suffering some form of age-related degeneration. In the grand scheme of things, doing just as well as a centenarian would be a large gain in life span for many, but it's simply nowhere near the outer limits of what is possible.

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Stem Cell Now Excerpt
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NPR is carrying a long excerpt from Stem Cell Now; looks like a good tabletop book for those seeking to better understand the science and prospects for therapies and healthy life extension: "Much of the promise of stem cells rests on a scheme for replacing parts worn out by age, injury, or infirmity. ... And thus may 21st century patients extend their lives - through a kind of patchwork medicine, held together by a fabulous, potent cell. ... Ten years ago, they said human organs couldn't be built. Now the challenge is unraveling the knotty problem of solid organs, like the liver, pancreas, heart, and lungs. ... He claims he can build a hollow organ in just five weeks: four weeks to expand the number of cells and one week to seed and build the 'construct,' the three-dimensional structure that becomes the organ."

Link: http://www.npr.org/templates/story/story.php?storyId=5204335

A Brace of Unrelated Articles
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In lieu of a coherent theme, I will point to a few articles that caught my eye today. Firstly, a short piece on the new Scripps Institute in Florida that has this to say on longevity:

We live in a world devoted to biomedical progress. As medical science has helped civilized humanity overcome the more common life threatening diseases in history, we now must turn our efforts toward conquering the more difficult disease states. These include neurological, genetic and malignant diseases.

This phase of research will entail delving into the genetic code and molecular cell levels of disease. The rewards would be significant. Treatment for crippling diseases, birth defects, paralysis, cancer and organ transplants that are not rejected are on the horizon. These life-saving treatments will ultimately add greatly to our longevity. The human being, under the best of circumstances, could increase life span by 30 percent or more. The answers lie in biomolecular research.

Twenty years of healthy life extension seems to be percolating through the scientific community as a plausible figure for the near future, attained through better therapies for age-related disease and general improvements across the board in medicine. This ties in nicely to yesterday's topic, timescales of incidental versus directed anti-aging medicine. If we take aim at the roots of age-related disease rather than fighting the ultimate symptoms of aging, we could make far better progress.

On to the next article: CBS is running a profile of Denham Harman, originator of the free radical theory of aging.

In 1954, Harman developed what now is the most widely accepted theory on the aging process, known as the "Free Radical Theory of Aging." In simple terms, the theory says a byproduct of oxygen use is adverse chemical reactions in cells. The result is aging and, ultimately, death.

The theory initially was, Harman said, "pooh-poohed and ridiculed" by the medical community.

...

"There was a long lag between him saying this was important and others doing the research to prove it," Potter said. "The fact he was the original has been lost. There's no disagreement that he said it first. But he has been under-recognized."

Modest by nature, Harman has focused his energies on pressing for research that leads to the enhancement of life for seniors. He is driven by a quote by 18th century satirist Jonathan Swift, who wrote: "Every man desires to live long, but no one would be old."

Interestingly, he is not an advocate of healthy life extension; rather, he falls into the compression of morbidity camp - aiming not to extend life span, but simply reduce the period of ill health at the end. I suspect that we're going to find that any medical technology that can extend healthy life span will extend overall life span, as suggested by the reliability theory of aging. Compression of morbidity taken to its logical extreme implies that one would die in perfect health - which seems rather silly on the face of it.

Onwards to the last of the articles for today: news from research into Werner's syndrome, one of a family of conditions with symptoms that either are or resemble accelerated aging.

Scientists know Werner is caused by a dysfunctioning gene, but Hu's unique approach to the research has furthered their understanding. Hu created the first 3-D structure of the gene, which might show how to fix the dysfunctioning gene and enzymes. Control of the enzymes could lay the groundwork for finding a cure for Werner.

...

"Hu's research is not a direct panacea to understanding the aging process by itself, because the aging that patients with Werner experience differs from usual aging," Martin said. "However, Hu's structure will be very helpful and it will be nice to see how it relates to the aging process."

Hu plans to research other parts of the gene further in hopes of finding more significant answers that could lead to the cure for age-related diseases or reverse the aging process completely.

"If we can try to understand [Werner], we can understand the aging process in general," Hu said.

The study of accelerated aging conditions such as Werner's syndrome and Progeria has led to progress in understanding the biochemistry of normal aging. This is a good thing.

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Olsen Interviews Kurzweil
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(Via KurzweilAI). This Sander Olsen interview with futurist Ray Kurzweil touches on radical life extension in the process of looking ahead at the coming technological singularity: "Nevertheless, the common wisdom is quite strong - even among friends and associates, the common wisdom regarding life cycle and the concept that life won't be much different in the future than it is today - still permeates people's thinking. Thoughts and statements regarding life's brevity and senescence are still quite influential. The deathist meme (that death gives meaning to life) is alive and well. ... By 2015, we will have real traction with nanotechnology. I believe that we will be well on the way to overcoming major diseases, such as cancer, heart disease, and diabetes through the biotechnology revolution that we talked above. We will also make progress in learning how to stop and even reverse the aging process."

Link: http://www.kurzweilai.net/meme/frame.html?main=/articles/art0643.html

Autophagy and Aging
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Autophagy is the process by which internal cell structures are dismantled; this PDF-format article from the end of last year takes a long look at the relationship between autophagy and aging: "A decrease in the turnover of cellular components and the intracellular accumulation of altered macromolecules and organelles are features common to all aged cells. Diminished autophagic activity plays a major role in these age-related manifestations. ... we review the molecular defects responsible for the malfunctioning of [two forms of autophagy] in old mammals and highlight general and cell-type specific consequences of dysfunction of the autophagic system with age. Dietary caloric restriction and antilipolytic agents have been proven to efficiently stimulate autophagy in old rodents. ... other possibly experimental restorative effects are discussed."

Link: http://www.landesbioscience.com/journals/autophagy/autophagypdf/a11820916767671121y00gf30471010/cuervoAUTO1-3.pdf?http://www.landesbioscience.com/journals/autophagy/autophagypdf/a11820916767671121y00gf30471010/cuervoAUTO1-3.pdf

Incidental SENS Versus Deliberate SENS, Timescales
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The Strategies for Engineered Negligible Senscence (SENS), put forward by biomedical gerontologist Aubrey de Grey, form a high-level scientific plan of attack, focused on the root causes of age-related degeneration. In essence, it is a declaration that scientists know enough and science is capable enough to move rapidly towards a cure for aging - and all age-related disease. I have this to say in the Longevity Meme introduction to SENS:

Progress in any one area of SENS science is likely to lead to therapies for a class of age-related diseases. It is not unreasonable to expect the research community - motivated as it is to seek cures for specific diseases - to slowly fill in the gaps in SENS as time moves on.

...

Making gains in SENS science in unrelated bits and pieces is likely to be a slow path for progress towards meaningful healthy life extension, however. Curing any one age-related condition is a wonderful thing for sufferers, but it will not increase healthy life span for anyone else - nor will it lead directly to therapies that can extend healthy life span without further investment and work. It would be much more cost-effective to directly address the root cause of aging and age-related disease.

Incidental rejuvenation of age-related cellular damage may just happen at some point as a matter of course, engineered in bits and pieces by a hundred different scientists working on a hundred different problems. As I point out above, however, don't expect "at some point" to arrive soon enough to be of any help to you personally.

Aubrey de Grey's proposed timeline for the direct, cut-to-the-chase approach can be found at the SENS website:

the first major SENS [milestone, reversal of aging, will] be achieved with laboratory mice. I also consider that it will be the point at which society becomes convinced that curing aging is very urgent, and that it will kick-start a genuine "War on Aging".

My estimate for the time until this milestone is reached, if there is adequate funding [of the order of $100 million / year], is ten years from now; almost certainly not as soon as seven years, but very likely to be less than 20 years. If funding is sluggish this could be doubled.

...

the second major SENS milestone [can] reasonably be defined as the arrival of therapies that confer a postponement and repair of human aging proportional to that described for mice in milestone 1, i.e. a tripling of our remaining life expectancy with therapies initiated on our late fifties or so. Inevitably I call this "Robust Human Rejuvenation" or RHR.

My estimate for the time until this milestone is reached, starting from the time that the mouse target is achieved, is 15 years; almost certainly not as soon as five years, and could be as much as 100 years. Note that this time I make no caveats about funding, because I think it is inconceivable that shortage of funds will be allowed to slow down this work once milestone 1 is achieved.

A number of us feel that the lower end of this range of timelines is impractical for simple business and commercialization reasons - it takes a decade to get anything out of a laboratory and to patients these days, and that looks to be getting worse before it gets better. Equally, the far upper end starts to look a little silly if you give any credence to Kurzweilian or similar views of the decades ahead - the technology curve four decades from now is going to be very impressive indeed.

The possession of impressive and advanced medical technology does not guarantee that we'll do all that we can with it, however. The laundry list of goals that could have been accomplished over the past 50 years - but were not - is a very long one. Supporting and advocating directed research that explicitly aims to greatly extend our healthy life spans is not a matter of hastening an outcome that was inevitable - it is a matter of ensuring that it happens at all.

100,000 lives are lost to the end results of aging with each and every day of delay, and hundreds of millions more suffer from age-related disease. We can do better than incidental healthy life extension - we can get out there and make it happen within our lifetimes.

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A Profile of the Buck Institute
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The Sacramento Bee profiles the Buck Institute for Age Research: "Today, 61 percent of the Buck's $25.6 million budget is supplied by grants, mostly from the government. The Buck Trust makes up 23 percent, donations 14 percent and licensing income, interest and miscellaneous the remaining 2 percent. That supports the work of 15 laboratories studying aging and age-related disease at the level of cells and genes. Lithgow, who left a tenured faculty position at the University of Manchester in England to join the Buck, said the allure of the institute is that everyone there agrees that the mechanism of aging - in and of itself - is worth trying to understand. Some do it through studying Parkinson's disease, others through human embryonic stem cells, or through cancer or nutrition or DNA damage."

Link: http://www.sacbee.com/content/news/science/story/14180827p-15008033c.html

Anything But Change
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Far too many people would rather suffer pain and death than admit radical change into their lives and the world at large; here is an Observer column from one such person. Fear of change makes for a poor futurist - if you don't like to think about the future in any meaningful way at all, you'll extrapolate very poorly. Hence this piece is a good example of many of the errors of thinking about healthy life extension that seem very hard to get rid of. In particular, the Tithonus error - that longer life will mean more infirmity rather than many more healthy, active years - and the idea that the present concept of retirement will continue as-is are featured prominently. I am reminded that people who don't like life are not likely to be enthused by more of it - but please let the rest of us get on with building a better, longer-lived future.

Link: http://observer.guardian.co.uk/comment/story/0,,1707903,00.html

Gene Therapy, Sequencing at The Scientist
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The Scientist has been putting out a quality product since their relaunch, and it's all open and free at the moment. All done to attract attention, of course, but one can hope they'll figure out a way to move forward without closing the blast shutters of paid registration once more. That does seem to be the prevailing business model for more traditional content producers these days, however - so enjoy it while it lasts.

With that in mind, let me point you to a few recent articles. I had commented already on the profile of aging researcher Judith Campisi:

Dealing with the accumulation of senescent cells is one of the seven Strategies for Engineered Negligible Senesence (SENS). This profile of researcher Judy Campisi at The Scientist gives some insight into where the mainstream of aging research is on this topic: "senescent cells not only exist in vivo but also accumulate in aging tissue. ... in culture, these nonreplicating cells are far from inert. They produce a plethora of unpleasant proteins that can, among other things, destroy the structural integrity of the tissue that surrounds them. ... The critical test would be to create an organism in which you prevent senescent cells from accumulating ... She and her colleagues are working on devising a system to do that test. They are developing a mouse in which an inducible promoter allows them to activate a gene that will selectively eliminate senescent cells."

Less immediately relevant to aging research, but still of interest to those who look ahead in medical technology, are these two pieces on genetic science.

Whither Gene Therapy?

A few successes notwithstanding, gene therapy remains highly experimental. Only a limited number of rare genetic diseases are candidates for gene therapy, and a few recipients have experienced severe adverse reactions from the treatment. Critics have argued that the technique has fallen short of its expectations.

Nevertheless, proof-of-principle studies showing that severe combined immunodeficiencies (SCID) can be corrected in a sustained way for a patient's benefit have been published.1,2 Some 20 patients now live as a direct result of genetic interventions. For the field to progress, and for that number to rise, we must learn from these successes what we did right, and from failure what went wrong. Only then can we make gene therapy safe enough and effective enough to become a routine component of the medical response to genetic diseases.

My Own Private Genome

But that's just one sequence pass, and according to vice president for molecular biology Michael Egholm, "It's simply ludicrous to say you can sequence a human genome with 1x coverage." He suggests 8x or 15x coverage, which would boost my costs to between $7.2 million and $13.5 million, and increase my sequencing time to about a year.

Another firm, Solexa, announced in December its plans to sequence a human genome in 2006. According to chief scientist David Bentley, "We're aiming for one billion bases per [two-day] run" on the company's new single-molecule sequencer, the 1G Genetic Analyzer. At that rate 15-fold genome coverage is just six months of work. Solexa has announced its sequencing of a 162,000-bp human BAC, but has yet to publish its findings in a peer-reviewed journal.

Bentley says Solexa will begin shipping instruments in the second quarter of 2006. Pricing has not been fixed, but, "We anticipate a similar unit price to a single high-end capillary electrophoresis machine, plus around $3,000 per run for reagents [initial costs]." He adds, "We're aiming to go to 30-fold coverage for $100,000."

There is a school of thought that says the cost of sequencing is a good measure for the state of play in bioinformatics as a whole - now that this has become a real race, I'm not so sure that continues to be true. It's certainly the case that you could pick a worse enabling technology to reduce to near zero-cost first of all - low-cost genome sequencing will enable all sorts of very impressive, targeted, effective medicine.

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Removing Senescent Cells
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Dealing with the accumulation of senescent cells is one of the seven Strategies for Engineered Negligible Senesence (SENS). This profile of researcher Judy Campisi at The Scientist gives some insight into where the mainstream of aging research is on this topic: "senescent cells not only exist in vivo but also accumulate in aging tissue. ... in culture, these nonreplicating cells are far from inert. They produce a plethora of unpleasant proteins that can, among other things, destroy the structural integrity of the tissue that surrounds them. ... The critical test would be to create an organism in which you prevent senescent cells from accumulating ... She and her colleagues are working on devising a system to do that test. They are developing a mouse in which an inducible promoter allows them to activate a gene that will selectively eliminate senescent cells."

Link: http://www.thescientist.com/2006/2/1/60/1/

DNA Repair, Mitochondrial Dysfunction
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Kevin Perrott comments on recent research into DNA repair and the effects of damage: "a DNA repair protein called NEIL1 coded in the nucleus had also been found in liver mitochondria implicating it, and possibly its relatives role, in the repair of mitochondrial DNA mutations. ... The researchers mutated both copies of NIEL1 in mice expecting an increased incidence of cancer but what they got were massively obese rodents with diabetes accompanied by liver and kidney disease and elevated of triglycerides in the blood, all hallmarks of metabolic syndrome. Hypothesizing that impaired mitochondrial function due to lack of NEIL1 function might be the cause, the confirmed that the mitochondrial DNA of the mutant mice indeed suffer from a great deal of breaks and damage." It is encouraging that work is underway to develop repair technologies for mitochondrial DNA.

Link: http://www.healthextension.net/archives/2006/02/metabolic_syndr.html

So What Is the Difference Between Drexler and de Grey?
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Glenn Reynolds made an interesting comment on the recent openDemocracy article that, at one point, compares biomedical gerontologist Aubrey de Grey to nanotechnology visionary Eric Drexler:

I think that de Grey is a bit naive in saying that because people are cordial and give him intellectual respect, he's safe. Drexler got the same respect and courtesy, until he didn't. ... De Grey is probably safe from such attacks, but it's because the political configuration is different.

Phil Bowermaster suggests:

I wonder if Aubrey is treated better because this issue strikes closer to home? We all have a vested interest in life extension. And it may be true that we also all have a vested interest in nanotechnology, but that isn't as readily apparent to most observers.

The attacks on Drexler - and on advanced nanomedicine at one point - were really quite beyond the pale. It was all a part of short-termist posturing on the part of certain pigs scrabbling at the government trough; pretty despicable stuff. Do prominent advocates for radical life extension have this sort of thing to look forward to in the future?

An analogous scenario for scientific anti-aging research would be if the moderates prosper - say that metabolic tinkering, an outgrowth of calorie restriction research, expands into a large industry with the real promise of 10 or 20-year healthy life extension. The industry spawned by these moderates, bolstered by publicity and public enthusiasm, then starts after major government funding ... but they decide that they need those darned advocates for radical life extension technologies - far beyond 10 or 20 year increases - to go away and stop scaring the fishes.

I think there is a credible case that we can obtain far, far better results than those derived from manipulating the genes and biochemical processes at the intersection of metabolism and longevity. It is a stepping stone, just as the nanotechnology industry of today is a stepping stone to far more impressive capabilities. It serves us all poorly for stepping stones to be sabotaging the pathway ahead - hopefully this will not be the case for the future of longevity research.

More than just hoping, I think we can do our part through advocacy aimed at ensuring that support for plausible research aimed at near-term results in radical life extension becomes the moderate, dominant position.

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On Inkjet Bioprinting
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ABC News catches up with research and development of inkjet technology for tissue engineering: "The promise of tissue engineering and the promise of 'organ printing' is very clear: We want to print living, three-dimensional human organs. That's our goal, and that's our mission. ... The concept behind organ printing is one that's been used in the manufacturing world for years, 'rapid prototyping.' ... Rapid prototyping is nothing more than layer-by-layer deposition of any materials. What is new is that instead of ceramic, instead of polymer, instead of some other nonorganic stuff, we use living tissue and living cells." The technology is in its very earliest stages - a long way to go yet, but it's most promising.

Link: http://abcnews.go.com/Technology/print?id=1603783

Review of the Genetics of Aging
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A review paper on genes, aging and drug discovery in the American Journal of Clinical Nutrition is interesting for having come from Elixir Pharmaceuticals staff: "Aging is not a passive activity, but an actively regulated metabolic process. Specific genes have been identified that regulate aging, although aging, and consequently longevity, is only partially under genetic influence. ... type 2 diabetes, a disease of glucose homeostasis, can be conceptualized as a form of accelerated aging. ... Because aging and diabetes are intimately related at a molecular level, diabetes may be able to provide the link between disease treatment (eg, diabetes) and the prevention of age-related diseases. If specific molecular pathways controlling the rate of aging can be modulated genetically, then perhaps they can be modulated pharmacologically."

Link: http://www.ajcn.org/cgi/content/abstract/83/2/466S

The Fish Are the Story
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Over at the Longevity Meme, I recently noted research on resveratrol - a compound that may trigger some of the same biochemical processes as calorie restriction - and extension of healthy life span in a species of short-lived fish, Nothobranchius furzeri:

Recently, a small fish species with a captive lifespan of only three months was described by Cellerino and colleagues. In the new work, the researchers used this short-lived fish to test the effects of resveratrol on aging-related physiological decay. The researchers added resveratrol to daily fish food and found that this treatment increased longevity and also retarded the onset of aging-related decays in memory and muscular performance ... Of course, there's always the possibility that they failed to control for actual calorie restriction - that happens a lot.

Regular readers already know I'm not big on the future of chemicals in pills and metabolic tinkering - they do not seem likely to get us anywhere near far enough in healthy life extension, as they don't touch on fixing age-related cellular damage. I found this most interesting for demonstrating that life span studies can be carried out in this species, at a fraction of the cost and time of comparative studies in mice. Fish are not mammals, of course, but they are a big step up from fruit flies in terms of the relevance of the science.

You might recall there was some talk of setting up a smaller research prize as a companion to the MPrize for anti-aging research in mice back in 2004. The prize could be smaller and still get results because it would be awarded for progress through less costly studies on short-lived creatures, such as, say, a Methuselah Fly Prize. A number of other species were suggested, Nothobranchius furzeri being one of them. Sadly, this all failed to go any further than the discussion stage, but one can hope that the discussion will be reopened as demonstrations like this study start to roll in.

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Genetic Influence on Life Span
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Scientists are starting pin down the bounds of the influence of genes on aging and life span, as demonstrated in this PubMed entry: "We study the genetic influence on human lifespan and how it varies with age using the almost extinct cohorts of Danish, Finnish and Swedish twins born between 1870 and 1910 comprising 20,502 individuals followed until 2003-2004. We first estimate mean lifespan of twins by lifespan of co-twin and then turn to the relative recurrence risk of surviving to a given age. ... While the estimated overall strength of genetic influence is compatible with previous studies, we find that genetic influences on lifespan are minimal prior to age 60 but increase thereafter. These findings provide a support for the search for genes affecting longevity in humans, especially at advanced ages." This goes nicely with the Reliability Theory of aging.

Link: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16463022

The Art of Overthinking
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More coverage of Demos and Better Humans can be found at Spiked, veering from sensible in places to knee-jerk overthinking in others: "It's because this area is really a debate about values that it is interesting. Do we want to live longer - if not, why not? How do we use technologies to extend ourselves rather than avoid ourselves?" I still find it amazing that some people are willing to expend so much effort to avoid concluding that curing disease, preventing pain and suffering, and offering people the choice of living longer, healthier lives are very good things. It's equally amazing that folk can even debate the possibility of blocking the development and use of healthy life extension technologies if they don't like your reasons for doing so.

Link: http://www.spiked-online.com/Articles/0000000CAF5E.htm

Demos, Better Humans, Supposedly Positive Bioethics
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I suppose I should mention again the Demos initiative "Better Humans? The politics of human enhancement and life extension"; those of us interested in healthy life extension should take a look at the following essays (in PDF format) from the collection:

You may find the rest interesting also. I've already had my say regarding Demos and this sort of school of supposedly positive bioethics in the latest Longevity Meme newsletter:

Demos, like so many other explicitly political ventures, has the air of operating in a world in which new technology simply falls from the sky or arrives by conveyor belt - ergo all efforts must go to simply responding to it. This is a nutty worldview, but one that is sadly all too prevalent. In fact, medical and healthy life extension technologies are far from certain, and the timetable for their arrival is even less determined. The future of our lives, of the length of our healthy life spans, is very much determined by what we do today - by how effectively we support medical research, and perhaps more importantly, the freedom to conduct medical research and make use of the resulting healthy life extension technologies.

This is not to mention the underlying assumptions of socialism that pervade the works, the most galling of which is that "society" (meaning anyone with political influence) has the right to stop progress in order for "society" (meaning bioethicists whose relevance and thus income depends on generating problems from thin air) to pontificate on what it all means. Such nonsense! Bioethics is the noise generated by various parasitic groups that thrive by slowing and blocking progress towards healthy life extension technologies. It's a sad thing that so many resources are wasted on building organizations and subcultures that contribute nothing of value, and are in fact incentivized to impede medical research.

Read through the Demos publications with this view in mind - you'll see that even supposedly positive, pro-research, pro-future bioethicists have little to add to actual progress in medical technology. They just damage it less than the luddites.

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Anti-Inflammatory News
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Inflammation is a major cause of some types of accumulated cellular and biomolecular damage, which is why sources of inflammation are linked to age-related conditions - acquire damage faster and your systems wear out faster. From EurekAlert: "We have done what many others have been trying to do for years. We have made a therapeutic antibody against one of the most potent inflammatory agents in the body and used it to cure arthritis in mice. The next step is to translate the highly effective outcome we see in mice to human patients. If we can do this, we will have a revolutionary new treatment for a number of important human diseases ... We anticipate that our antibody will be a significant improvement over current therapies because it acts at a different and earlier point in the inflammatory process compared with current anti-inflammatory therapies."

Link: http://www.eurekalert.org/pub_releases/2006-02/ra-ssd020706.php

Seizing the Chance To Live To 150
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More coverage of biomedical gerontologist Aubrey de Grey, the path to radical life extension and transhumanism - as seen by the Demos think tank - can be found at the Financial Times: "As medicine becomes more powerful, we will inevitably be able to address ageing just as effectively as we address many diseases today ... equally significant are the ripples of interest that Mr de Grey is generating outside the scientific community. He has rapidly emerged as the British figurehead of a new political movement, which has steadily been gaining ground on both sides of the Atlantic. This movement is known as transhumanism, and its central belief is that advances in science and technology will liberate us from the constraints of illness and ageing and enable us to live longer, healthier lives."

Link: http://news.ft.com/cms/s/8230ef1a-9847-11da-816b-0000779e2340.html

Aubrey de Grey on Radio 4
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Biomedical gerontologist and healthy life extension advocate Aubrey de Grey made an appearance on BBC Radio 4's Start the Week yesterday. A Real Media format download for the show is also available.

DEMOS are launching a collection of essays exploring the politics of human enhancement and life extension featuring an interview with the Cambridge scientist, DR AUBREY DE GREY, who describes why he believes that the first person to reach 1000 years old may already be alive and why this is something we should strive for. The collection is called Better Humans? and is published by Demos and the Wellcome Trust.

A couple of commentaries from the all-seeing, all-hearing blogosphere are up already:

Would you want to live to be a thousand years old?

But what of living to be 1,000? Clare demonstrated the sort of politician she is by seemingly failing to listen to what Dr Aubrey de Grey was saying and angrily coming up with all sorts of instant objections.

let's live forever

However the most interesting response to de Grey is opposition. Other panellists responded "why should we want to live to 200", "what is wrong with frailty?" and talked about overpopulation. I think these responses - which I shared the first time I considered this issue - are not only missing the point but are frightening. All medical technologies could be similarly doubted, and it would be hideous to do so. What de Grey anticipates are medical technologies so effective they make our present technology seem like leeches and a hole in the head. We are largely resigned to dying in our first century, this is better than spending a life in fear of death. But it doesn't mean that death in the our first century is desirable.

If you don't want to live to 200, you can take the way out any time you choose. We find suicide terrible, but perhaps we should find natural death terrible, and respect the chosen death after a long life, celebrating the fact that nature did not intervene sooner.

But what about overpopulation? What about healthcare, including the costs of and access to longevity technology? What about pensions? These will be significant challenges, but not so significant I think that we should seek to kill everybody off at the age of 80 by suppressing the technology.

It's interesting - and promising in its own way - to see those who would once have been in the naysayer camp now rationalizing their way to common sense (in the form of a pro-longevity, pro-research stance) as the prospects for radical life extension in our lifetime become more rosy. It demonstrates that we're on the right track - we just need to pick up the pace.

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Review of "The Long Tomorrow"
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A positive review of evolutionary biologist Michael Rose's "The Long Tomorrow" can be found at the American Scientist: "The [premise] is that the ultimate cause of senescence is natural selection and that evolutionary biology holds the key that will unlock the secret of longer, healthier lives for humans. ... Rose and his colleagues have succeeded in bringing about this paradigm shift by weight of evidence and prolific publication of articles, mostly in top-tier peer-reviewed journals. Most scientists studying senescence now accept the rather remarkable idea that natural selection accounts for such a seemingly maladaptive trait, although there is still debate over the specifics of some mathematical models and the interpretation of some data. Rose was not alone in his efforts to move evolutionary biology to the forefront of aging research, but as outlined in this book, he was the first to publish compelling data."

Link: http://www.americanscientist.org/template/BookReviewTypeDetail/assetid/49559

Genes and Alzheimer's
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Forbes reports on the genetic component of Alzheimer's: "Genes may play a much bigger role in Alzheimer's disease than previously thought, a new study involving twins suggests. In fact, Alzheimer's disease may have a genetic cause in up to 80 percent of cases ... The study, which involves data on nearly 12,000 elderly participants in the Swedish Twin Registry, is 10 times larger than any previously done." From what researchers presently know, Alzheimer's is the end result of biochemical processes that take place in everyone. Your genes likely determine the rate at which harmful side-effects accumulate, and the degree to which you resist that harm. Live long enough and you'll suffer neurodegeneration - which is why curing Alzheimer's and other age-related neurodegenerative conditions is so important for the future of healthy life extension.

Link: http://www.forbes.com/lifestyle/health/feeds/hscout/2006/02/07/hscout530854.html

Stem Cells Versus Type 2 Diabetes
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(From Medical News Today). A modest study on type 2 (age-related) diabetes using the patient's own stem cells shows good results: "84% of the patients that had received the autologuous bone marrow cells could also abandon the drugs that stimulate insulin production or the insulin that they had been receiving previously. There were no complications at all, demonstrating the safety of the technique ... The most likely reason of this improvement is that the implanted autologuous stem cells regenerate the destroyed beta cells in the Islets of Langherhans in the pancreas of diabetes patients. It is also possible that they originate new beta cells which produce the new insulin."

Link: http://www.medicalnewstoday.com/medicalnews.php?newsid=37226

Kurzweil, Radical Life Extension at the Futurist
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A PDF version of a recent Futurist piece by Ray Kurzweil and others on the coming technological singularity - and the associated prospects for radical life extension through a variety of means - can be found online:

We are in the early stages of the genetics revolution today. By understanding the information processes underlying life, we are learning to reprogram our biology to achieve the virtual elimination of disease, dramatic expansion of human potential, and radical life extension.

...

Genetic and molecular science will extend biology and correct its obvious flaws (such as our vulnerability to disease). By the year 2020, the full effects of the genetic revolution will be felt across society. We are rapidly gaining the knowledge and the tools to drastically extend the usability of the "house" each of us calls his body and brain. Nanomedicine researcher Robert Freitas estimates that eliminating 50% of medically preventable conditions would extend human life expectancy to 150 years. If we were able to prevent 99% of naturally occurring medical problems, we'd live to be more than 1,000 years old.

...

Billions of nanobots will travel through the bloodstream in our bodies and brains. In our bodies, they will destroy pathogens, correct DNA errors, eliminate toxins, and perform many other tasks to enhance our physical well-being. As a result, we will be able to live indefinitely without aging.

As before, I think the Kurzweilian timescale is aggressive for reasons relating to our ability to successfully manage complexity. There's nothing wrong with the basic concepts, however - these classes of technological capabilities will come to pass, quite possibly within our lifetimes. If this is the case - if we work today to ensure that it is the case - then our healthy life spans could become long indeed.

Kurzweil's message to luddites, conservatives and others who whitewash and romanticize the past is one to listen to here, I think. It's very much to the point:

We don't have to look past today to see the intertwined promise and peril of technological advancement. Imagine describing the dangers (atomic and hydrogen bombs, for one thing) that exist today to people who lived a couple of hundred years ago. They would think it mad to take such risks. But how many people in 2006 would really want to go back to the short, brutish, disease-filled, poverty-stricken, disaster-prone lives that 99% of the human race struggled through two centuries ago? We may romanticize the past, but up until fairly recently most of humanity lived extremely fragile lives in which one all-too-common misfortune could spell disaster. Two hundred years ago, life expectancy for females in the record-holding country (Sweden) was roughly 35 years - very brief compared with the longest life expectancy today, almost 85 years for Japanese women. Life expectancy for males was roughly 33 years, compared with the current 79 years. Half a day was often required to prepare an evening meal, and hard labor characterized most human activity. There were no social safety nets. Substantial portions of our species still live in this precarious way, which is at least one reason to continue technological progress and the economic improvement that accompanies it. Only technology, with its ability to provide orders of magnitude of advances in capability and affordability, has the scale to confront problems such as poverty, disease, pollution, and the other overriding concerns of society today. The benefits of applying ourselves to these challenges cannot be overstated.

In the present day we live in a world in which hundreds of millions suffer daily from age-related disease, and a hundred thousand die every day. We are within a few decades of eliminating this suffering, but each day of delay carries a huge toll in lives and pain.

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Resveratrol News
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I'll admit to being skeptical on resveratrol, despite some interesting science lurking in there somewhere - the compound appears to pull some of the same biochemical triggers as calorie restriction. This EurekAlert report looks at research in short-lived fish: "Recently, a small fish species with a captive lifespan of only three months was described by Cellerino and colleagues. In the new work, the researchers used this short-lived fish to test the effects of resveratrol on aging-related physiological decay. The researchers added resveratrol to daily fish food and found that this treatment increased longevity and also retarded the onset of aging-related decays in memory and muscular performance." Of course, there's always the possibility that they failed to control for actual calorie restriction - that happens a lot.

Link: http://www.eurekalert.org/pub_releases/2006-02/cp-rpl020206.php

Reviewing Business Economics and Longevity Research
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Researcher Leonid Gavrilov has moved his blog, Longevity Science. One of the recent posts in its new home is a draft review of "The Quest for Human Longevity: Science, Business, and Public Policy", published last September. Comments are requested, so take a look:

Most other popular books on human longevity are focused almost exclusively on scientific ideas and breakthroughs in life-extension research, and they typically avoid any money talks as inappropriate subject. ... This somewhat idealistic perspective is challenged in a new book, which describes in a great detail how important money is in modern entrepreneurial world of life-extension and anti-aging research business. The book provides an alternative, more realistic perspective that financial incentives are driving scientific innovations in anti-aging studies by stimulating researchers to take risks and to work really hard.

"The Quest for Human Longevity" goes beyond traditional curtains of financial secrecy when it describes the detailed history of eight corporations that were pursuing anti-aging and life-extension interventions recently -- Geron Corporation, Juvenon, Eukarion, BioMarker Pharmaceuticals, Elixir Pharmaceuticals, Helicon Therapeutics, Memory Pharmaceuticals, and Cortex Pharmaceuticals. Particularly interesting are the candid profiles of their scientific founders and top executives, which include Michael West, Bruce Ames, Stephen Spindler, Saul Kent, Cynthia Kenyon, Leonard Guarentee, David Sinclair, Eric Kandel and other prominent leaders and scientists.

Finance and economic behavior are indeed at the heart of everything - all the education, advocacy and activism surrounding healthy life extension is intended to craft an environment in which research funding is easier to come by (and in larger amounts), after all. In essence, we are trying to make more people aware of an economic proposition that is clear to us - that sufficient investment in real anti-aging research will bring huge returns.

Beyond that, thinking about the healthy life extension community and its progress in economic terms helps to make clear much that would otherwise be confusing. Why do certain ventures fail? Why is a particular field of research funded while others languish? Why does the disreputable "anti-aging" marketplace exist? Following the real and hypothetical paths of investment and profit, financial or otherwise - who pays, who benefits - is very much the way to understand the world of human action.

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A Look at Telomere Research
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(Via EurekAlert). The tools of modern biotechnology are becoming ever more capable, as illustrated by this narrow view into telomere research: "Cancer researchers have long sought a way to subdue telomerase, an enzyme whose excessive activity contributes to the unchecked growth of as many as 90 percent of human tumors. ... In most healthy adult cells, telomerase is shut off, and telomeres slowly shrink during cell division - a normal process that helps limit cells' lifespan. Cancer cells, however, usually find a way to turn telomerase back on, achieving a dangerous immortality. ... We now have a detailed picture of the part of telomerase that forms this anchor site, and in fact have identified a groove within the protein that is what is really holding on to the end of the chromosome ... A molecule that would sit in that groove - even though it's far away from the active site - looks like it would completely abolish the ability of telomerase to work."

Link: http://www.eurekalert.org/pub_releases/2006-02/hhmi-gpe020106.php

$100 Million For Stem Cell Research
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What's the point of success and wealth if you don't use that wealth to make a difference? There's certainly something to be said for the era in which governments didn't tax to the hilt and so more wealth could go to philanthropy rather than waste. Forbes reports that Michael Bloomberg has donated $100 million to research: "It is thought the donation will support research at the school's Institute for Cell Engineering, where scientists are doing work that could lead to the use of stem cells - undifferentiated cells which retain the ability to differentiate into other cell types - as treatments for conditions such as Parkinson's disease, diabetes and spinal cord injuries."

Link: http://www.forbes.com/2006/02/03/bloomberg-billionaires-philanthropy-cx_cn_0203autofacescan02.html

An Impressive Jump In Efficiency
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The limiting factor in much of modern biomedical research - beyond government interference, that is - is the rate at which biochemical mechanisms, compounds and genes of interest can be identified as starting points or linked to medical conditions. Given such a starting point, research is startlingly fast, but obtaining that starting point can be slow indeed. So this news from EurekAlert is a very welcome and impressive advance: researchers have "developed a method that could speed up the process of identifying novel protein molecules for medical or biological research hundreds of times over. ... Searches that now take a year to complete can be done in a matter of days. ... The results from a screen completed in one afternoon were equivalent to those previously obtained through several rounds of mutation and screening - a several-month process."

Link: http://www.eurekalert.org/pub_releases/2006-02/acft-wtc020206.php

On Epigenetics
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(From CMAJ). Things are always more complex than you think in biochemistry and medical research; if you have a grasp of genetics as it relates to aging, the next thing to add to your plate is epigenetics: "Epigenetics refers to the study of heritable changes in gene expression that occur without a change in DNA sequence. Research has shown that epigenetic mechanisms provide an 'extra' layer of transcriptional control that regulates how genes are expressed. These mechanisms are critical components in the normal development and growth of cells. Epigenetic abnormalities have been found to be causative factors in cancer, genetic disorders and pediatric syndromes as well as contributing factors in autoimmune diseases and aging. In this review, we examine the basic principles of epigenetic mechanisms and their contribution to human health as well as the clinical consequences of epigenetic errors."

Link: http://www.cmaj.ca/cgi/content/full/174/3/341

Healthy Life Extension Videos: Google, YouTube
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Immortality Institute volunteer liveforever22 has been busy pulling together video clips of interest to healthy life extension supporters and uploading them to the new online video distribution networks. You'll find a list of links in the resources section and more in a related discussion thread:

Television interviews by Aubrey de Grey:

CBC Interview of Aubrey de Grey 5:53 in length

"Richard and Judy" show Aubrey interview 6:33 in length

"Good Morning" Aubrey interview 7:23 in length

Conference presentations by Aubrey de Grey (minus the Imminst conference, which is below):

Poptech conference presentation 45:06 in length - pretty low quality video, but worth seeing just for the musical intro by Johnathan Colton (who is terrific in and of himself)

TedGlobal conference presentation 29:59 in length - I hadn't watched this till I uploaded it, but it is a very good overview especially for people who have never heard of Aubrey

ImmInst Conference Videos:

Intro to the conference 4:17 in length - Bruce doing his thing

Martine Rothblatt 18:33 in length - Legal Rights of Conscious Computers

Brad Mellon 17:09 in length - This would be a good one to show to any of your religious or Christian friends

Aubrey de Grey 29:49 in length - Anti-Aging

...

Along with the other one on YouTube ( http://www.youtube.com/?v=guo5LmkOu6o ) I put up the 60 Minutes interview as well:

http://www.youtube.com/watch?v=_0jO5okttC4

Which, to my surprise, is already a "top viewed" video the morning after I put it up there. It could be helped by some more people voting 5 stars for it, (if you have the time).

I also put a higher quality version on Google Videos (YouTube limits size to 100MB, so I had to cut down the quality for them) but they are still verifying it at the moment. I'll let you guys know when it goes live.

Feel free to pass these links around far and wide. Short videos are an excellent way to introduce your friends to healthy life extension - and show why it's important to support and encourage the future of medical research. With the right approach and large scale funding, age-related degeneration could be defeated within our lifetimes.

If you're sitting on any other videos of interest, then get them uploaded! There's no reason not to share; online video networks are a great tool for spreading information about healthy life extension and winning new support for greater funding of anti-aging medical research.

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Radical Life Extension, Step by Step: the Packaging of an Important Concept
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The idea of achieving radical life extension - living healthily not just for additional decades, but centuries or even longer through advanced medical technology - by successive steps is far from new. It's been a part of modern transhumanist discussions of healthy life extension for as long as those discussions have been taking place. The concept is very simple: if a new technology can give you 20 extra years of healthy life, then you could benefit from the end results of another 20 years of further medical research and development. The application of those end results will extend your healthy life span again, and so it continues. If medical technology advances rapidly enough - a big if - then your life span will no longer be limited by disease and aging; you will have beaten the curve.

For all that this concept has been around for a long time, it has suffered from a lack of good packaging for public consumption. Ideas have to have a certain shape to make progress in our idea-saturated culture. This a terrible shame - it's a great concept, very intuitive and attractive once grasped. It's certainly simple enough to spread widely if explained well, but take a look at one of my attempts back in 2004:

If regenerative medicine can give us 30 extra years of healthy life, then we will have time to develop working medical nanotechnology - it will be 2050 already! While regenerative medicine is largely a matter of manipulating existing proteins, genes and cellular mechanisms to heal, nanomedicine promises to use tiny machines to do all that far more efficiently and with greater degrees of control and effectiveness.

Beyond nanomedicine...well, nanomedicine will give us many healthy years to think about what comes next.

This, in a nutshell, is the bootstrapping process: extending healthy life span faster than we age. It's a realistic goal for modern science. Not an easy goal, but a realistic one.

The bootstrapping metaphor didn't quite work. Elsewhere, and more recently, Ray Kurzweil and Terry Grossman use the metaphor of bridges - "a bridge to a bridge to a bridge" - in Fantastic Voyage. Biomedical gerontologist Aubrey de Grey and some other healthy life extension advocates have settled on "actuarial escape velocity":

An interesting scenario was thus unexplored: that in which mortality rates fall so fast that people's remaining (not merely total) life expectancy increases with time. Is this unimaginably fast? Not at all: it is simply the ratio of the mortality rates at consecutive ages (in the same year) in the age range where most people die, which is only about 10% per year. I term this rate of reduction of age-specific mortality risk 'actuarial escape velocity' (AEV), because an individual's remaining life expectancy is affected by aging and by improvements in life-extending therapy in a way qualitatively very similar to how the remaining life expectancy of someone jumping off a cliff is affected by, respectively, gravity and upward jet propulsion.

We're all searching for the right handle, the right hook by which this concept will spread far and beyond the cultural conversation about healthy life extension. People respond very positively to the idea of radical life extension via actuarial escape velocity - it's a great meme for encouraging support and understanding of our goals. We need to work on the packaging and delivery, however.

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Aubrey de Grey in openDemocracy
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A long and interesting profile of biomedical gerontologist Aubrey de Grey and his work can be found at openDemocracy: "Ageing isn't much fun, getting decrepit and senile. You have to find some way of putting it out of your mind. But we're talking about the extension of healthy life, not just extending old age. Psychologically it's terribly difficult for people to take on board that this is something worth fighting for ... He thinks people will eventually come round to his way of thinking, arguing that the media's fascination with his theories tells you something about the pent-up demand for longer, youthful lives. ... the secret to longer life lies in the research lab. ... De Grey's media persona, reflected in the growing canon of articles about him, fails to do justice to the subtleties of his position, and the strategic flair with which he is influencing a debate that may, just may, turn out to be one of the defining issues of our time."

Link: http://www.opendemocracy.net/debates/article.jsp?id=6&debateId=27&articleId=3237

Aging and Senescent Cells
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Here we have research to support the role of accumulated senescent cells in degenerative aging: "There is good evidence that senescent cells are not benign. But until now, no one has been able to confirm that they exist in appreciable numbers in old animals. ... the Brown team began to study aging animals - baboons living on a research preserve that ranged in age from 5 to 30. In human years, that age range is roughly 15 to 90. ... For replicative senescence, the most important biomarker is telomere dysfunction-induced foci, or TIFs. Presence of these structures signals that the protective chromosome caps called telomeres have dwindled enough to halt cell division. ... What they found: The number of senescent cells increased exponentially with age. TIF-positive cells made up about 4 percent of the connective tissue cell population in 5-year-olds. In 30-year-olds, that number rose as high as 20 percent."

Link: http://www.brown.edu/Administration/News_Bureau/2005-06/05-071.html

TED2006, February
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Biomedical gerontologist Aubrey de Grey will be at this year's TED conference, a sort of networking event for the hyper-networked. "It brings together more than 800 thought-leaders, movers and shakers. ... This unique breadth of content, and the quality of people who deliver it, are what make TED special. After four days, you gain an understanding of how your own work fits into the larger web of knowledge. And you get the chance to connect with extraordinary individuals who are helping create a better future for us all." I certainly can't think of a better recipient for the TED Prize, but I might just be a little biased in my choice of priorities for the future - better medicine, greater research, far longer, healthier lives.

Link: http://www.ted.com/conference/flashpage.cfm?conferenceKey=2006

Meanwhile, Over at FuturePundit...
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The commentary in a couple of recent posts by Randall Parker over at FuturePundit should be of interest to readers here:

X Prize For DNA Sequencing Announced:

I am all for orders of magnitude faster and cheaper DNA sequencing. However, I question the granularity of this prize. I'd rather see prizes for advances in microfluidics and other technologies that would be for goals that can be achieved more quickly and which could be done by smaller groups. Multiple research teams could very easily make contributions that get used in the final effort to win this prize and yet not be the actual team that travels that final distance. University groups with limited resources that are working on various aspects of the larger problem but not on pieces big enough to solve the entire problem aren't going to be incentivized by this prize.

...

Of course, the coolest prize with the most relevance to the eventual stopping and reversing of the aging process is the Methuselah Mouse Prize for finding ways to make laboratory mice live longer. The latter article above even quotes Methuselah Mouse Prize cofounder David Gobel who some of you have noticed posting in the comments section of FuturePundit posts. The general buzz big new prize announcements helps promote each prize.

I, too, had comments to make on this X Prize announcement. It seems a touch odd to be encouraging something that clearly needs little encouraging - few branches of research are moving as rapidly as the present pace of bioinformatics (questions of organization aside). But onwards; have a look at these posts too:

Human Embryonic Stem Cell Research Labs Very Isolated:

My expectation is that this is the new status quo on human embryonic stem cells (hESC) research in the United States. We'll have a group of isolated human embryonic stem cell labs working away on human pluripotent stem cells derived from hESC for years to come. Eventually the barrier between these researchers and the rest of biomedical research community will break down due to one of two reasons: A) research advances will lead to ways to make pluripotent stem cells without using an egg as a starting point or B) the value of hESC for producing therapies will become so clear to the public at large that a large majority will decide that their ethical reservations aren't all that deep and that it is in their own self interest to accept therapies made from embryonic stem cells.

Immune System Rejuvenation May Partially Rejuvenate Brain:

The brain is the organ in the body which is going to be hardest to rejuvenate. We will not be able to replace the brain since it contains our individual identity. By contrast, some day we'll be able to grow replacements for other organs in the body such as the liver, kidneys, heart, or pancreas. Since the brain is the hardest target for rejuvenation I'm always heartened by any research that suggests avenues to explore to develop brain rejuvenation techniques. A team of researchers in Israel have made discoveries that suggest rejuvenation of the immune system might some day provide a way to partially slow or partially reverse the aging of brains.

I'm not alone in the opinion that dealing with the aging brain is going to be one of the toughest challenges facing the development of radical life extension within our lifetimes. Groundwork taking place today -like the Allen Brain Atlas - will prove essential, but present methodologies of medical research and development must yield to a better approach:

This prospect of unending discovery of new failure modes - and the long development of a cure, all too late to save those unlucky enough to be at the head of the queue - is one of the reasons that an engineering approach to fixing age-related disease is so attractive. Rather than play catch-up and research with ever more complex consequences of age-related cellular damage, let's identify, repair and prevent that damage. Strike at the root, in other words, by taking the path of greater effectiveness and least complexity. If we can do that, there would be no need to determine and decipher the fatal neurodegenerative conditions that follow Alzheimer's - no-one will ever accumulate the damage required to suffer from these presently unknown killers.

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The Importance of Medical Tourism
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(Via Medical News Today). Competition with other regions is one of the few things likely to slow the sad decline of Western medical research and development of commercial therapies into an over-regulated, motionless morass. Efforts like FasterCures are also important, but only the overwhelming evidence of being left in the dust - with inferior medical technology - is likely to motivate bloated modern governments. So rising medical tourism is a very good thing; it's the most visible sign that someone, somewhere has escaped from crushing regulation in order to make real progress in curing disease, bringing costs of treatment down, and extending healthy life spans.

Link: http://www.medicalnewstoday.com/medicalnews.php?newsid=36914

Two Years and Onwards
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This February 1st marks two years of Fight Aging! - at a post per day, every day. Not too bad, even if I do say so myself; it doesn't seem that long since I started off with "welcome aboard." Many thanks are extended to the guest authors who helped me keep up that average in earlier days - such as Phil Bowermaster from the Speculist - as well as to those who've linked and commented. It goes to show; writing is like any good habit, in that it becomes a great deal easier to keep up as time goes on.

This seems like an appropriate time to talk about the purpose of this blog: a conversation is presently taking place on the topic of healthy life extension, although it may not always look like a conversation in the traditional sense. It wends its way throughout human interactions and publications; articles, magazines, websites, blogs, actual physical conversations, letters public and private. It is a single pathway in the great marketplace of ideas and culture.

Sometimes our conversation is hard to find, however. People who might have learned and contributed do not do so; opportunities to broaden the healthy life extension community are lost. This has been very true in the past, but new technologies have brought great changes in this as in so many other things. Simple email was impressive enough, but this second phase of the World Wide Web, and the technologies and culture of the blogosphere in particular, are perhaps the most effective medium for this form of conversation yet devised.

For all that, someone has to be talking on topic to keep the conversation growing, to avoid lapses in which newcomers might miss the party - hence the existence of Fight Aging! The more the merrier, however. If you have things to say about healthy life extension and the future of real anti-aging medicine, then pull up a keyboard and get typing. You live in an era of marvels, in which it costs next to nothing beyond your time to place your thoughts in front of thousands of people. What are you waiting for?

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Mitochondria Under Calorie Restriction
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(From PubMed). The practice of calorie restriction (CR) makes for better, more efficient mitochondria it seems: "Age-related accumulation of cellular damage and death has been linked to oxidative stress. ... Mechanisms responsible for the antiaging effects of CR remain uncertain, but reduction of oxidative stress within mitochondria remains a major focus of research. ... We have focused our research on a related, but different, antiaging mechanism of CR ... mitochondria under CR conditions show less oxygen consumption, reduce membrane potential, and generate less reactive oxygen species than controls, but remarkably they are able to maintain their critical ATP production."

Link: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16446459

Aubrey de Grey in Life Extension
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Life Extension Magazine profiles biomedical gerontologist Aubrey de Grey: "Dr. Aubrey de Grey of Cambridge University is widely considered the fastest-rising star in the field of biogerontology, the area of science devoted to what happens to organisms as they age. Dr. de Grey (everyone calls him 'Aubrey') stands out not only because of his brilliance and dedication to the elimination of aging, but also because of his exceptional energy and organizational abilities. He serves as editor-in-chief of the peer-reviewed journal Rejuvenation Research, has established a scientific prize (now approaching $2 million in value) for extending the lives of mice by rejuvenation or other means, and has recently held a second international conference of first-class researchers in biomedical gerontology at Cambridge University."

Link: http://www.lef.org/magazine/mag2006/feb2006_profile_01.htm

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Benefiting from Medical Research

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