Odds and Ends

A somewhat random collection of links for you folk today; my attention is wandering far and wide. Let's start with a fairly content-free piece of research promotion via News-Medical.net. These things, while somewhat frustrating, are a good indicator as to what those in the know really think about rates of progress and potential for funding. The latter is a fair proxy for general sentiment in the field and chance of success, if you play the averages.

The technique involves growing cells inside a 'non-reactive biocontainer' which, placed in rats, sees the cells mature into fully functional tissues and organs. Using this breakthrough technology, scientists at BOBIM have successfully produced sufficient tissue to replace a breast.

...

Professor Morrison sees the new approach having potential for repairing many other tissues and organs including muscle (skeletal and beating heart tissue), organoid (pancreas and liver) and glands (hormone secreting, pituitary and sinus).

Moving on, more commentary spurred the recent TransVision 2006 conference, courtesy of queerrel:

Even if the first human to live a 1000 years had indeed been born already, it would take some great amount of time before these technologies could be put to use to benefit the rest of the humankind. This in turn gives us a fair amount of time to solve the overpopulation problem, which, and I can't emphasize this enough, we'll have to solve anyway. So why wait till we've got everything figured out - I have faith in the on-going evolution of the creative spirit of the humankind, so to say.

Another lecturer pointed out the concern some seem to have of becoming very bored if having to live that long. "Well", he said, "if life is boring, then certainly death is going to be even more boring!"

Moving on again, a couple of posts on that recent BBC article that took a brief scan of viewpoints on radical life extension. Attila Csordas rightly notes the poll; while all online polls should be taken with a grain of salt, I don't think I'm imagining the trend of ever more support for ever more healthy life.

The supporters of life extension are not just transhumanists and the members of present day health and beauty establishment.

And more:

If we can make it to 1000, we will have achieved immortality. We won't have to worry about "illness"; we'll worry about altogether bigger threats such as the lifetimes of stars, the hard radiation of supernovae, the gnarled topology of spacetime, and, ultimately, the fate of the universe itself.

Even if you think Ray Kurzweil is way off in his predicted timescales, the technology of a hundred years from now is going to be most impressive. A thousand years on? Hard to think about except in the broadest terms of capabilities; physical immortality is certainly on that list. I don't think anyone is seriously arguing that it can't be done these days, rather the debate is over the very crucial matter of timing. How much, and how soon?

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Gene Therapy, Cancer, Progress

Good news in the quest to develop practical immune therapies to defeat cancer: "researchers have successfully treated cancer patients by genetically modifying their immune cells to attack tumors. Although the treatment worked in only two of 17 patients, the researchers say this proof of concept [should] pave the way for more gene-therapy cancer cures. ... In 15 of the patients, the injected cells thrived and made up at least 10% of their total T cells weeks later. Two men who had even higher levels of the modified T cells experienced a dramatic recovery. In one, a liver and armpit tumor that had developed from spreading melanoma cells shrank, and in the other a lung tumor disappeared. Both men remain healthy 18 months after treatment ... One important result is that the treatment didn't seem to cause a serious autoimmune response as a side effect." The success rate will improve: the lack of side effects indicates a viable platform for broader development and sophistication.

Link: http://sciencenow.sciencemag.org/cgi/content/full/2006/831/3

The BBC On Radical Life Extension

The BBC is running a general interest article on radical life extension and the supporters of greater research to this end: "there is disagreement between scientists about the possibilities for life extension. ... Some believe that new developments will allow us to rise above our nature and live for hundreds of years, others think the improvements in life expectancy will be incremental ... If we continue to make medical and scientific breakthroughs, why shouldn't life expectancy rise even further over the next 100 years?" Those callous voices arguing for a future of billions of avoidable deaths - people aged to death in a thousand horrible ways because we did not develop the technologies to help them - make their usual unwelcome appearance towards the end of the piece.

Link: http://news.bbc.co.uk/2/hi/uk_news/magazine/4809992.stm

Aging Would Be Wonderful...

Aging would be wonderful ... if it could just be separated from age-related degeneration. This Mexia Daily News article captures something of the feel of that truth, even as it somewhat misses the point along the way - and downplays the real suffering that comes with our present inability to repair the decline of our aging bodies. Growing older means becoming more experienced, wealthy, independent, wise, and just plain better at this game called life. Advancing age also means living into even more impressive eras of new technology aimed at enhancing life, progress and happiness. The aim of healthy life extension research - and the long term goals of radical life extension - is to have all this on top of the health and vigor of youth. It's a plausible, attainable goal, and we should all be working harder to make it a reality.

Link: http://www.mexiadailynews.com/variety/local_story_242111652.html

Life Span: You're In Control

(From the International Herald Tribune). Scientists are turning up longevity genes, but that doesn't mean your life span is heavily predetermined now: "only 3 percent of how long you live compared to the average person can be explained by how long your parents lived. You really learn very little about your own life span from your parents' life spans. That's what the evidence shows. Even twins, identical twins, die at different times ... on average more than 10 years apart. ... there was almost no genetic influence on age of death before 60, suggesting that early death has a large random component - an auto accident, a fall. ... even though there may be a tendency in some rare families to live extraordinarily long, the genetic influence that emerged from the studies of twins was significantly less than much of the public and many scientists think it is." All the more reason to work on increasing your chances of living to see the anti-aging medicine of the future.

Link: http://www.iht.com/bin/print_ipub.php?file=/articles/2006/08/30/news/aging.php

"It Sounds Hard, I Don't Like Change, So Let's Stop People From Doing It"

All too many people in the world see the boundaries of the possible end at what they can conceive. I noticed an op-ed piece on the tremendous benefits of embryonic stem cell research by one such character today. The digest version would be "it sounds hard, I don't like change, so let's stop people from doing it." The normal flaws of logic, leaps of faith, ignorance of economic realities, and callous disregard for human suffering and death - dolled up as concern - are in evidence. See for yourself:

One tribe of Native Americans had a saying that the old must die so the young could have their chance to live on the land. We seem about to implement a technology that will have exactly the opposite effect. For the sake of our posterity, once considered sacred but now apparently considered disposable or at least available to be saddled with the financial and emotional care of an ever-expanding geriatric population, let's give this "better living through embryos" mentality a really thorough once over before there's no turning back.

How easily some folk dispose of humanity as soon at it becomes remotely incovenient for their worldview! I have real trouble identifying with a mindset that would sacrifice billions to suffering and death in the name of a poorly defined abstract concept. There are no abstract concepts. There are only individuals - individuals, including us, including this callous writer, who will suffer and die unless progress is made.

The sole merit in this piece is that it correctly identifies the main issue with fixating all resources on one line of medical technology.

It's a fact that all of us eventually will wear out, but we generally do so at a different rate for each organ system. A 70-year-old may have a really good set of kidneys but a ticker that has seen better days, or a superb bony framework and a set of lungs that barely oxygenates him when he is at rest, and a sensory system that doesn't allow him to see or hear. Restoration of one or a couple of parts would not necessarily guarantee a prolonged period of independent, healthy living.

Not to mention the immune system, the brain, miscellaneous tissues that are hard to replace, biochemical changes in mitochondria, genes and telomeres, and so forth. Stem cell based regenerative medicine is not a single solution for aging; it cannot be. Much, much more must be done - but that is no excuse to shy away from moving forward with any area. Partial benefits are far better than no benefits, no matter what some few callous people say. The same arguments in this op-ed can be applied to all cancer research, all advances in surgery, all new medicine in fact. "It's hard, it's a partial solution, I can throw together a few objections, better not move forward."

Sadly, the author has an "M.D." after their name. With the attitude towards human suffering and death on display there, I'll be damned if I can see how that happened.

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More On AMD and Genetic Risk

(From EurekAlert!). Researchers continue to characterize genetic risk of developing age-related macular degeneration (AMD): "Variations in the BF/C2 gene are protective for AMD, whereas the more common variations in the other two genes, CFH and LOC, increase risk of AMD. The authors provide new calculations that one's lifetime risk of AMD ranges from less than 1% to more than 50%, depending on the variations one has in these three genes. The research team also showed that the three genes do not interact, but confer risk independently." The next step is to determine the biochemistry underlying these correlations, a process that is, fortunately, proceeding ever faster in these years of advanced biotechnology. Every aspect of the aging body is a system; decipher it and many doors will open for medical development.

Link: http://www.eurekalert.org/pub_releases/2006-08/hms-vi3082906.php

Heart Disease, Aged Arteries

An example from the BBC of the relationships between age-related conditions and greater biochemical wear and tear on specific organs. "The experts identified telomere damage - a biological sign of DNA ageing in the smooth muscle cells of diseased blood vessels. In patients with heart disease, the artery cells divided up to 13 times more rapidly than normal, prematurely ageing them. When artery cells age, they are less able to prevent fatty deposits from forming. This can narrow the arteries and cause heart attacks. ... The older the tissue, the less able it is to deal with physical or biochemical injury." Age is used very loosely in this article to reflect damage and reduction in capabilities. Some damage leads to age-related conditions; other damage leads to more and different damage. Failure of age-damaged biology can be a cascade - you should read up on reliability theory as it applies to aging and your body.

Link: http://news.bbc.co.uk/1/hi/uk/5291642.stm

Turning Down Inflammation

Chronic inflammation is bad for your long term health and longevity. Inflammation as a system is pretty complex, but scientists are making good progress in understanding just how it all works - in painstaking detail. This opens the door for the existing drug development infrastructure and community to attempt to turn down inflammation in any number of ways; in theory, and as for early nanomedicine in cancer research, the attempts should become ever more directed, precise and lacking in side effects as the science advances.

At the moment, a number of groups are focusing on the biochemistry of cytokines such as tumor necrosis factor alpha (TNFa, cachexin or cachectin). Interfering in the operation of cytokines seems to be a promising method for controlling the inflammatory response. A few examples in development:

QR-433:

QR-443 is an all natural broad spectrum anti-inflammatory compound that is being concurrently studied as a drug for Rheumatoid Arthritis (under the designation QR-440) in humans and dogs. QR-443 has been shown in previous pre-clinical studies to inhibit the production of TNFa and IFN gamma

As yet unnamed:

Devgen scientists have discovered compounds that inhibit the secretion of specific hormones that are the primary cause of rheumatoid arthritis, an autoimmune disease that causes chronic inflammation of the joints. ... following encouraging results from studies in animals, one of its preclinical programs may show promise for the treatment of inflammatory diseases. ... A key competitive edge of the Devgen molecules is that they are small molecule drugs that can be orally administered. The current treatments are protein based therapeutics, applied by injection and are costly to produce. Hence, they are infrequently administered early in the development of the disease. ... Finding orally active TNFa inhibitors is a 'holy grail' in inflammation research as it may provide patients with convenient, cost effective and hence earlier treatment options in the development of these progressive diseases

Filter out the standard press release hype; the interesting point is that groups are working on these sorts of solutions. Many will fail, some will succeed. As knowledge grows and the tools become better, the solutions will also become better - and cheaper and more widely available. The direction here is towards ever more effective, precise and knowing control over our biochemistry, in this case to prevent an existing system from running out of control and shortening our lives.

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Progress In Understanding Cellular Differentiation

Progress in understanding - and then controlling - the mechanisms of cellular differentiation has been rapid in the past year or two. The more that is learned, the closer we come to advanced regenerative medicine, capable of repairing or replacing any diseased tissue to order. Along the way, just as for cancer research, all that is learned about our cells can be taken and applied to meaningful anti-aging science. Today, I ran across a couple of examples of the sort of work presently taking place:

Wnt Protein Helps Stem Cells Specialise:

The lining of the respiratory and gastrointestinal tracts, the pancreas, the liver, the thymus and the thyroid all have their origin in a structure of the early embryo called the anterior endoderm. Josh Brickman and his team have shown that, in the African clawed frog, the anterior endoderm forms through a cascade of activities of different molecules, leading, ultimately, to the increased activity of a protein called Wnt.

They then used mouse embryonic stem cells to demonstrate that the same cascade exists in mammals and to suggest that this activity of Wnt might be exploited to contribute to current efforts to direct embryonic stem cells to become pure anterior endoderm cells. This would be the first step in obtaining, for example, liver cells and insulin-producing beta cells of the pancreas, in the laboratory.

This next article is particularly exciting; modern tools are enabling deep and detailed insight into the way in which our cells actually work.

Decision-Making Circuitry of Blood Stem Cells Mapped:

There is a lot of excitement in stem cell biology these days about the possibility of rationally and efficiently generating particular cell types from different stem cells for therapeutic purposes. As we better understand the underlying genetic circuitry that orchestrates development of a particular kind of stem cell into a specialized cell type, we should be able to manipulate it for such purposes.

...

A major scientific puzzle, said Singh, has been how and why immature hematopoietic stem cells initially express genes that are characteristic of more than one cell lineage. "One can imagine that the cells are molecularly previewing their developmental options by turning on at low levels cell-type-specific genes, and thereby revealing the developmental potential that they have," said Singh.

Understanding the circuitry that controls this critical "transcriptional priming" is central to understanding how different kinds of stem cells develop and what kind of developmental potential they have

Read the whole thing - it really is very promising. Biochemistry is always more complex than you think at first, but the veils are falling away ever more rapidly. Twenty years from now, a range of very impressive regenerative medical technology will result from these first steps.

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Technology Review on Living Longer

The MIT Technology Review staff has grouped together recent articles on aging, age-related disease and healthy life extension - including that infamous and opinionated article on biomedical gerontologist Aubrey de Grey and the Strategies for Engineered Negligible Senescence, as well as the results of the $20,000 SENS Challenge - into a section on living longer: "Technology Review examines the emerging technologies in biomedicine, genetics and medical devices that will change medicine over the next 10 years. These new technologies promise to detect diseases earlier, lead to far more effective drugs, and help us understand what causes diseases."

Link: http://www.technologyreview.com/special/living/index.aspx

A Little Monday Science

A few interesting review papers are listed at Ouroboros today: "The nematode Caenorhabditis elegans represents a superb model system in which to study the effects of mitochondrial function on longevity. Several mutant strains have been identified that indicate that mitochondrial function is a major factor affecting the organism's lifespan. Taken as a group, these mutant strains indicate that metabolic rate, per se, only affects longevity indirectly ... Insulin signaling, mitochondrial respiration, and dietary restriction share conserved roles not only in the regulation of lifespan, but also in the timing and control of diverse functions such as reproduction, stress resistance and metabolism. These autonomous pathways differ in their dependence on known transcription factors and in their temporal requirements, but converge to manipulate the core set of physiological systems necessary for extended lifespan in worms."

Link: http://ouroboros.wordpress.com/2006/08/28/reviewing-the-reviews/

The Sabotage of Excessive, Wasteful Caution

A good example of a call for caution that would, if enacted, amount to a form of sabotage can be found amongst the essays of the Healthful Life Project. It's a good illustration of the way in which some of those who might appear at first glance to be in favor of healthy life extension are in fact putting forth a message little different from the rhetoric of the more obvious opposition.

Surely common sense would suggest that excessive population growth is very likely to have some very unpleasant consequences, and that the health and prosperity of humankind, as well as other creatures that share the planet with us, is likely to require that population be stabilized at some reasonable level (say 10 to 12 billion persons). If that notion is accepted, then it follows that the greatest threat to achieving population stability at reasonable levels will not be a failure to control birth rates, but rather the extension of adult life span. That, in turn, invites the conclusion that the greatest threat to planetary stability is within the scientific community.

...

I would suggest that we concentrate on conquering diseases and slowing the aging process so people can live out their maximal physiologic life span. That will benefit individuals; it will simultaneously challenge the global society as average life expectancy increases by 20 or 30 years, but with a reasonable amount of thought and planning, we can cope with those changes. On the other hand, we should approach changing the boundaries of aging with great caution, insisting on debating the questions I posed at the beginning of this essay and requiring that any attempt to change the boundaries in human beings be kept experimental and be accompanied by rigorous long-term assessment that includes evaluating the quality of life of these very old persons.

In sum, my view is: Maximizing physiologic life span - full speed ahead. Changing the boundaries of human aging - go slow with extreme caution. The research into aging is spectacular, but the implications and potential consequences are so profound that we cannot afford to leave it solely in the hands of the scientific community. We had better figure out where we are going or we may find some unpleasant surprises when we get there.

The Malthusians are convinced that the sky will fall if people live longer or use more resources. Never mind that overpopulation through longevity seems just as unlikely to come to pass, judging by the data we have on hand: Malthusians been convinced of this for quite some time - and proven absolutely wrong in their specific predictions time and time again. Here's a newsflash for the Malthusians: it's too late; the sky has already fallen. We are already in the midst of a disaster far greater, immediate and proven than any postulations about population on your part. What is more, you fail to understand the nature of change and are ignorant of economics; your actions will only prolong this present disaster by blocking progress.

More than 100,000 people died yesterday - and the day before, and the day before that. More than 100,000 people will die tomorrow, and the day after, and the day after that - and forever on unless we do something. They are dying of aging, of root causes that scientists are comparatively close to understanding and addressing. It takes a particular sort of mindset to put future issues based upon an ignorant view of human action and economics in front of this present ongoing toll. Personally, I'm glad I do not think that way.

The precautionary principle is a distillation of inaction forced by excessive caution. More extreme expressions of the precautionary principle have been seized upon and promoted by all sorts of opponents of progress because they represent a halt to all progress: no advance is ever risk-free. Demanding - and attempting to enforce - risk free progress is one and the same with halting the engine of science and technology. Many foolish people want just this, sadly, and would condemn every living person to suffer and die from degenerative aging to achieve their ends.

Sadly, the popularity of extreme expressions of the precautionary principle obscure the high costs of adhering to even moderate versions. If you attach a ball and chain to those working on medical progress, medical progress will be slow. How can anyone advocate slowing down progress in the face of 100,000 deaths each and every day? Yet this seems to be the mainstream position; those who do not contribute to getting the work done have largely fallen down the rabbit hole of doing nothing but throwing roadblocks in the path ahead. Great job, you all - I hope you manage to live with yourselves if scientists create working anti-aging medicine within our lifetime despite your efforts. If science is held back well enough ... well, then we all age, suffer and die. Well done. Applause. A pity you won't be there to receive the gratitude of the masses - who won't be there either.

A couple of years ago, the Proactionary Principle was proposed as an answer to all this anti-progress waffling and nonsense:

People's freedom to innovate technologically is highly valuable, even critical, to humanity. This implies several imperatives when restrictive measures are proposed: Assess risks and opportunities according to available science, not popular perception. Account for both the costs of the restrictions themselves, and those of opportunities foregone. Favor measures that are proportionate to the probability and magnitude of impacts, and that have a high expectation value. Protect people's freedom to experiment, innovate, and progress.

I think it continues to stand as a much more sensible viewpoint. The sky has fallen, and we see tens of millions of deaths each year: we should be moving the earth and sky to do something about it.

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Inflamm-Aging, Cytokines and Aging

The "inflammaging" meme is gaining traction as illustrated by this review paper (even if no-one can agree on the spelling). "In this article we summarise present knowledge on the role of pro-inflammatory cytokines on chronic inflammation leading to organismal aging, a phenomenon we proposed to call "inflamm-aging". ... On the whole, despite some controversial results, the available data are in favour of the hypothesis that pro-inflammatory cytokines play an important role in aging and longevity. Further, we present a possible hypothesis to reconcile energetic dysfunction, including mitochondria, and inflamm-aging." From the reliability theory point of view, inflammation is generating unrepaired cellular damage - the more damage, the earlier you'll likely age to death. Accumulated damage is aging. Fortunately, most of us have a great deal of control over the major source of chronic inflammation in our life - our excess body fat.

Link: http://www.ingentaconnect.com/content/ben/cpd/2006/00000012/00000024/art00014

Advancing Scaffold Technology

From Xinhua Online, a look at one area of progress in scaffold technology for tissue engineering: "If you put a soup of these cells on to one of our scaffolds, they sort themselves out into the right order ... Although the mechanism is not fully understood, the cells seem to be programmed to rearrange themselves into layered normal skin. These simple scaffolds helps the cells grow in a safe yet natural way. Over the short life of a skin scaffold, mimicking nature too closely isn't necessary. ... Having realized that smart cells with a dumb scaffold is the key, the professors and their team are perfecting a dissolvable skin scaffold for skin growth. It will be made from clinically-approved materials such as PLGA, a dissolvable polymer used in surgical stitches, and undergo clinical and laboratory testing over the next three to five years ... [the team] may go even further than skin grafts. They're also looking at scaffold technology to promote nerve or tendon growth."

Link: http://news.xinhuanet.com/english/2006-08/26/content_5008756.htm

The Complexities of Cancer

This ScienCentral article and video is a great example of the way in which cancer research is driving our understanding of human biochemistry. What we call cancer is, in essence, a laundry list of runaway failure modes in the very complex biochemical machinery within our cells. If you want to prevent a machine from breaking down, or repair a failure in process, it helps to have the relevant blueprints to hand. By the time cancer is reduced to the status of costly but non-fatal chronic condition - perhaps as soon as 2015, at least for the most common classes of cancer - if seem likely that our understanding of cellular biochemistry will be nearly complete. If cancer research produces blueprints for human biochemistry, scientific anti-aging research - and every other field of modern medicine - will certainly run with them.

Link: http://www.sciencentral.com/articles/view.php3?type=article&article_id=218392841

On Regenerating Cartilage

The Houston Chronicle takes a look at work to regenerate cartilage, in the knee in this case: "Doctors are testing new ways to spur cartilage to regrow in damaged knees, from implanted 'cartilage plugs' to injections of bone-marrow stem cells. ... Knees are the joint most likely to go bad, and the cartilage that cushions them has only a limited natural ability to repair itself. ... new options are being tried first in people who injured their knees and thus need small amounts of cartilage to regrow. But if they truly work, the techniques one day might offer hope for arthritis sufferers, too, whose cartilage over time erodes. Most eagerly anticipated: the first clinical trial using stem cells from donated bone marrow to try to regenerate the knee's shock absorber, a cartilage pad called the meniscus."

Link: http://www.chron.com/disp/story.mpl/headline/nation/4132133.html

Raising Awareness, Making Material Progress

We need more people in the community who get out there and write as a matter of course - it broadens the conversation and helps to raise awareness of plausible near term gains in healthy life extension. It also helps to wake people up from the knee-jerk acceptance of age-related degeneration and knee-jerk condemnation of attempts to lengthen healthy life span. This is very important. So let me open with a quote from one of Anne C.'s latest posts:

At any rate, while I don't think it's "important" to get everyone all excited about cyborg implants and do-it-yourself gill slits and other potentially cool modifications that might happen at some point in the future, I do think it is a very good idea to try to break people out of the "pro-aging trance", at least those who think that since they can't fathom living indefinitely nobody else should be allowed to even attempt it.

The ones who just want to age out and die, but who are perfectly fine with the idea of other people trying to avoid that fate are probably harmless (and when they see those around them living longer, healthier lives they might start reconsidering anyway!) But in order to serve as examples of what a healthy, extended life could be, first we need the means to achieve those extended lives. And I am happy to report that I've become involved in part of a very cool project that could potentially contribute to real anti-aging science (I don't want to say too much yet, but I will say that I'm tremendously excited and looking forward to any opportunity in this realm.)

As noted, we also need more people to start in on getting the work done. Twenty or thirty years from now, people will look back and see that it was the vast funding from source X or Y that made all the difference in the development of first generation healthy life extension medicine and the research infrastructure to support further gains. That funding has not yet come to pass. It isn't going to come to pass without (a) success in raising awareness, educating the public and creating the right atmosphere of understanding and support, and (b) success in pilot projects that seek to attain meaningful early milestones in healthy life extension science.

The ideal progression sees modes (a) and (b) advancing in parallel and supporting one another. If one side moves too far ahead of the other, it loses efficiency and effectiveness: it's hard to grow support for year after year without ongoing material progress to point at; it's equally hard to raise minor funding for pilot projects without sufficient widespread support and understanding.

Thus, activist and advocacy groups forge alliances with researchers. None of this is rocket science or a new path forward. For groups like the Methuselah Foundation and its supporters, the only novelty lies in the degree of success enjoyed for the topic at hand: an effective, scientific path forward to longer, healthier lives.

It has become very clear that this is the right time for this activism and new science to make significant gains. If we want to live to see a future of far longer, healthier lives, then we need to get our shoulders behind the wheel of progress.

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More on Understanding Differentiation

Understanding cellular differentiation is a key to progress in regenerative medicine. From EurekAlert!: "mesenchymal stem cells, which regularly reside in the bone marrow as part of the body's natural regenerative mechanism, depend on physical clues from their local environment in order to transform into different types of tissue. The researchers were even able to manipulate stem cells by changing the firmness of the gel on which they were grown. ... stem cells sense their environment through the force it takes them to push against surrounding objects. ... the amount of force the stem cell needs to move its cellular muscles triggers an internal chemical signal that, in turn, directs the cell to differentiate. ... cardiac tissue may have been so damaged during the heart attack that the stem cells do not recognize the microenvironment as a guide for turning into heart muscle ... it might be possible to 'prime' stem cells for therapy in the lab, before implanting them in the heart, spine or whatever damaged environment you want to place them."

Link: http://www.eurekalert.org/pub_releases/2006-08/uop-uop082306.php

Cryonics in Australia

Via the Herald Sun efforts to set up a cryonics provider in Australia: "Biologist Philip Rhoades has won approval from health authorities to build the complex - believed to be only the third in the world. ... My parents are both science types, like me, and with my siblings are interested in this great experiment. If I can eventually help other people whose lives should be longer, this would also be a good thing to do. ... He said there was a need for a cryogenic centre in Australia because US religious fundamentalists could sabotage operations in the US or a more conservative US government might outlaw the process." Regulatory hostility to cryonics in much of Europe would suggest that all it takes is a large government willing to interfere in your life - and any large government will do just that. This said, it is good to see a higher profile for cryonics and the science behind it resulting in efforts like this one and KrioRus in Russia.

Link: http://www.news.com.au/heraldsun/story/0,21985,20256064-661,00.html

Update on VesCell and TheraVitae

While wandering the web, I bumped into an educational article on the continuing development and application of the VesCell therapy from TheraVitae in Thailand. I've noted this topic previously, both as an important advance in first generation regenerative medicine and in the context of the natural end result of costly, wasteful, useless regulation in the US. But take a look at the article:

Doctors in the United States at the University of Pittsburgh and the Texas Heart Institute, among others, also are conducting early stem-cell therapies to heal the heart, according to the National Institutes of Health clinical trials site.

"I would like to see randomized trials," comparing it with other established treatments for the heart, Schechtmann said. "Not immediately, but in the next three to five years, hopefully, we will see some significant discoveries."

Don Margolis, one of TheraVitae's founders, said the company has almost completed a clinical study, involving 24 patients, in which investigators are looking at ejection fractions -- a measure of how well the heart pumps -- and patients' stamina, as determined in a six-mile walk, to assess the therapy's success.

Because the last patient to enroll has not been followed out six months, he said, no data has been published yet.

"But overall, our success rate is 70 to 80 percent, as measured by how the patients themselves feel" after treatment, he said. "At least half feel markedly better; another 25 percent feel somewhat better or no worse; and 25 percent have little benefit."

I should note an example of a knee-jerk reaction from those used to the days in which US medical research led the world:

He also got a second opinion from another heart doctor in Brevard County, as well.

"He said, 'If it was worth anything, we would be doing it here,' " Strickland recalled.

If we permit socialism and regulation to continue to destroy the incentives for investment, research and quality in the US, we'll see far more examples of the best new development happening elsewhere. Alongside far more examples of folk in denial of that truth, no doubt.

Researchers will develop - are already in the process of developing - far better and more effective medical technologies than VesCell. But it's hard to commercialize and deploy better medicine with the weight of the FDA resting on your neck.

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Interesting Alzheimer's Research

A number of threads in Alzheimer's research are focusing on areas other than the amyloid plaques characteristic of the condition. Via EurekAlert!: "Treatments that elevate the [protein] ubiquitin C-terminal hydrolase L1 (Uch-L1), [might] have potential as a new therapy for Alzheimer's disease ... we were able to restore a great deal of brain activity in a transgenic mouse model of Alzheimer's disease ... While amyloid beta is certainly a key player in Alzheimer's disease - and efforts to reduce it remain a worthy goal - our results show that, even in the presence of the plaque, damage to memory can be reversed ... Ubiquitin is a 'tag' that marks proteins for destruction by the cellular 'garbage disposal' known as the proteasome, Shelanski explained. Uch-L1 acts as the proteasome's 'gatekeeper' ... the brains of Alzheimer's disease patients show an accumulation of ubiquitin-tagged proteins, suggesting some defect of the protein degradation machinery."

Link: http://www.eurekalert.org/pub_releases/2006-08/cp-bet082106.php

An Effective Diabetes Treatment?

The New Scientist reports on a potential treatment for type 2 diabetes: "obesity triggers insulin resistance by inducing stress in a cellular organelle called the endoplasmic reticulum (ER). ... It is thought that obesity causes stress in the ER by forcing it to process an excessive amount of fat molecules. ... [researchers] decided to try supplying the ER with extra chemical chaperones, in the form of small molecular drugs called PBA and TUDCA. Mice with severe obesity and insulin resistance were given one of the two drugs for three weeks. ... In both sets of mice, blood glucose levels returned to normal within four to seven days, the researchers say. And the drugs restored insulin sensitivity and cured fatty liver disease in the 'diabetic' mice. The normal glucose levels remained constant until the end of the treatment." Another effective methodology: take better care of your health so as to avoid obesity.

Link: http://www.newscientist.com/article/dn9840-new-hope-for-treating-obesityrelated-diabetes.html

Don't Bow Down to Those Who Would Steal Your Freedom

It's a simple motto to try to live by: no appeasement; don't bow down to those who would steal your freedom. It's increasingly hard to live that way, of course, what with armies of government employees willing to apply force to back up any number of cages upon your behavior. But it's human nature to want to live free, just as, sadly, it's human nature to shrug when forcing the loss of freedom upon others. This might go a little way to explaining the mixed reception to Advanced Cell Technology's latest technology demonstration:

researchers at Advanced Cell Technology have created a line of such cells from a single human embryonic cell. Unlike existing methods, the procedure leaves the embryo viable, raising the possibility it could be widely used to create embryonic cells without destroying embryos.

Advances in the efficient development of stem cell lines are important - researchers will likely need access to thousands of lines in the course of developing therapies and cures through embryonic stem cell research. This demonstration was presented in more of a political context, however:

There is now no rational ethical argument against stem cell research, now that we can preserve the embryo," he says. "The existing cell lines are weak, they're old, there are too few of them, and they are difficult to maintain. What we wanted to do with this process was to ensure that there are enough lines available. This should give the entire field a boost."

This strikes me as an attempt to mollify people who are not really all that rational when it comes to their opposition to stem cell research. This is not a sound strategy, and I'm not alone in that view:

the idea that blastomere derived cell lines are an 'alternative' to embryonic is quite simply all hype. ... the only people who will let you pull a blastomere off of one of their embryos are people who dont plan to use them anyway!

...

some of these scientists are worried about showing any acquiescence to the anti-abortion folks who have been campaigning against embryonic stem cell research.

If you're going to fight for your freedom of research (and fight we certainly should), then don't fight on their terms and their ground. The freedom to research human cellular biochemistry is essential to rapid progress towards the medicine of the future. Without the results of this research, tens of millions will die every year from age-related diseases and conditions that might already have been cured.

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Ouroboros at the MPrize

I'm pleased to note that Chris Patil's Ouroboros now joins the extremely informal blogging collective gracing the homepage of the MPrize for anti-aging research. Welcome aboard!

Given that Telomolecular is in the press of late, alongside interesting research on telomere length and stress, you should take a look at the latest Ouroboros post on telomere science:

One of my fantasies (and I think it should be the fantasy of every biogerontologist) is to be able to walk up to a human subject with my handy futuristic and minimally invasive device, and make a measurement to determine how old they are. I don't mean their chronological age, but rather how old they are really - let's call it "physiological age", a value that would (in the fantasy) be more powerfully predictive of risk for age-related disease and decline. Intuitionally and anecdotally we know that different people simply age at different rates, but at the moment it's painfully hard to quantify what we mean by that.

I don't necessarily think telomere measurements are a magic biomarker bullet, but these results make me wonder whether they might end up being an important part of the toolkit.

You'll find more on the search for low-cost biomarkers for aging back in the Fight Aging! archives. It's worth noting that the SENS approach advocated by biomedical gerontologist Aubrey de Grey is something of an end-run around this absence of easy biomarkers, amongst other things. If you have any interest in living a longer, healthier life, you should read up on it.

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On Telomolecular

Telomolecular are setting out to raise their profile in the community, judging by the contents of this Yahoo! press release: "Nanocircles (a nanotechnology developed at Stanford University) and vTert (Telomolecular's synthetic enzyme) are capable of repairing damaged and shortened telomeres. Researchers at Telomolecular believe they've found a way to deliver Nanocircles and vTert to chromosomes in living organisms, reversing diseases caused by that damage. The researchers envision the ability, eventually, to speed the healing process in humans, preventing or even curing cancer." The devil is always in the details of implementation; a number of companies and research groups are forging ahead in attempts to establish telomere-based therapies for cancer and other age-related conditions.

Link: http://biz.yahoo.com/prnews/060823/clw514.html

Nanotechnology for Biomaterials

A long and rather densely written article from AzoNano.com examines the use and future of nanoscale engineering to develop ever more capable biomaterials for regenerative medicine: "Third-generation biomaterials that involve tailoring of resorbable polymers at the molecular level to elicit specific cellular responses show great promise as scaffolds or matrices in tissue regeneration. ... bioactive glasses and macroporous foams can be designed to activate genes that stimulate regeneration of living tissues. ... a future goal for regenerative medicine is the possibility of using bioactive stimuli to activate genes as a preventative treatment; maintaining the health of tissues as they age. Only a few years ago this concept would have seemed unimaginable. But we need to remember that only 30 years ago the concept of a material that would not be rejected by living tissues also seemed unimaginable!"

Link: http://www.azonano.com/Details.asp?ArticleID=1703

Biological Pacemaker Research

EurekAlert! notes that scientists continue to make progress towards replacing artificial pacemakers with biological equivalents: "Our study offers positive and direct evidence in living models that bioengineered cells can replace the electronic pacemaker. Our hope is to one day replace electronic pacemakers in people ... In the current study, the researchers delivered a gene encoding a bioengineered cell-surface protein to heart muscle cells of pigs. This protein mimics the combined action of several proteins called HCN ion channels, which play a critical role in maintaining a normal, evenly paced heartbeat. ... through gene expression, normal muscle cells of the heart were converted into pacemaker cells [in a matter of days] by a process called transdifferentiation. Studies done two weeks after the injections showed the new [pacemaker cells] were able to take over pacemaking function."

Link: http://www.eurekalert.org/pub_releases/2006-08/uocd-udr082106.php

Piling the Bad News Atop the Evidence Atop the Excess Fat

Any excess fat is not good for you; it shortens your life, increases your medical expenses and leads to suffering and age-related disease. The scientific evidence for that statement piles ever more weighty with each passing year - much like the unrepaired cellular damage at the root of aging that your body fat helps to accumulate in your tissues.

With that in mind, here is another round of support for the common wisdom of good health:

Being a little overweight can kill you, according to new research that leaves little room for denial that a few extra pounds is harmful. Baby boomers who were even just a tad pudgy were more likely to die prematurely than those who were at a healthy weight, U.S. researchers reported Tuesday.

While obesity has been known to contribute to early death, the link between being overweight and dying prematurely has been controversial. Some experts have argued that a few extra pounds does no harm.

However, this is one of the first major studies to account for the factors of smoking and chronic illness, which can complicate efforts to figure out how much weight itself is responsible for early death.

"The cumulative evidence is now even stronger," said Dr. Michael Thun, chief epidemiologist of the American Cancer Society who had no role in the research. "Being overweight does increase health risks. It's not simply a cosmetic or social problem."

A separate large study of Korean patients, also released Tuesday, reached the same conclusion. Both are being published in this week's New England Journal of Medicine.

Relatedly, and via the Gerontology Research Group list, you might take a look at this recent study of supercentenarians performed by some of the list folk:

Age range was 110 to 119. Fifty-nine percent had Barthel Index scores in the partially to totally dependent range, whereas 41% required minimal assistance or were independent. Few subjects had a history of clinically evident vascular-related diseases, including myocardial infarction (n=2, 6%) and stroke (n=4, 13%). Twenty-two percent (n=7) were taking medications for hypertension. Twenty-five percent (n=8) had a history of cancer (all cured). Diabetes mellitus (n=1, 3%) and Parkinson's disease (n=1, 3%) were rare. Osteoporosis (n=14, 44%) and cataract history (n=28, 88%) were common.

...

Data collected thus far suggest that supercentenarians markedly delay and even escape clinical expression of vascular disease toward the end of their exceptionally long lives. A surprisingly substantial proportion of these individuals were still functionally independent or required minimal assistance.

There is a lesson to be learned here: a large portion of the the burdens of age-related disease are not a matter of luck. Yes, longevity genes exist, but much of your future is a matter of metabolism and the cellular damage that results. You have a great deal of control over this process across a lifetime; remember that there are no fat people amongst the extremely old and hale. The overweight succumb to diseases and damage resulting from their metabolism long before they can become centenarians, let alone supercentenarians.

Your genes won't be under your control for another few decades, but weight is a choice for most of us, and an important one at that. We live on the cusp of great transformations in medicine and biotechnology - but the dead will be dead and the future of greatly extended healthy longevity is lost for those who fall before we get there. Don't be one of the dead; that choice is most likely in your hands.

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Australian Stem Cell Politics

COSMOS provides an overview of recent stem cell politics in Australia, alongside some of the science: "In 2002, George Daley at the Children's Hospital in Boston and colleagues at the Massachusetts Institute of Technology used [therapeutic cloning] to cure a mouse with bone marrow failure by providing it with a perfectly matched bone marrow graft. A nucleus from a cell at the tip of the mouse's tail was rebooted to develop as an embryo, which provided embryonic stem cells. Those embryonic stem cells were guided to form healthy bone marrow, which was grafted back into the mouse. End result: the mouse's bone disease was cured with its own cells, sparing it the need to use anti-rejection drugs or the possibility of a fatal rejection." Much of the most promising stem cell research is flat-out banned in Australia; supporters hope to see this changed in the near future.

Link: http://www.cosmosmagazine.com/node/580

A Key to Better Immune System Control?

Scientists believe that chronic inflammation or an overactive immune response - and the long-term damage it causes to health and longevity - might be controlled with greater subtlety than is presently possible. "The [interleukin-27 (IL-27)] cytokine limits the duration and intensity of white blood activation, an 'off switch' to the cascade of messenger proteins that serve to further activate the immune system. ... Without IL-27, other brakes in the system are not sufficient to keep inflammation in check ... The more we understand the role of cytokines in the immune system, the more we realize that they are part of an elaborately balanced system kept in check by the conflicting regulatory functions of the cytokines themselves. ... It may be possible to use IL-27 or its active subunit in such a way that we can temper the immune system without suppressing the beneficial immune reactions."

Link: http://www.upenn.edu/pennnews/article.php?id=993

Stroke and Neurogenesis

Does the adult human brain grow and integrate significant numbers of new neurons? Yes, no and maybe, depending on which scientists you ask - but it certainly has the capability to do so. From Newswise: "It appears the human brain attempts to heal itself by giving birth to new neurons following a stroke. This finding, by scientists at the Buck Institute for Age Research, confirms similar studies in animal models and offers new targets for therapeutics to aid stroke recovery. ... The researchers found that cells surrounding the stroke-damaged area carried molecular markers of neurogenesis. In addition, the newborn cells were predominantly located near blood vessels, which have been shown to produce factors that boost cell division and growth. ... The fact that several drugs have stimulated new nerve growth in rodents, suggests that clinical interventions might be developed to enhance this process in humans."

Link: http://www.newswise.com/articles/view/522863/

AIDS-Damaged Immune Systems and Aging Immune Systems

As I've noted in the past, it seems a number of strategies under development to repair or offset damage done by AIDS to the immune system may also - at some point in the future - be usefully applied to declines in the aging immune system. At least some of the underlying damage is similar in both cases. A recent release from Geron has this to say:

The new studies demonstrate that our orally available telomerase activator drug broadly reactivates anti-HIV immunity in AIDS patients' lymphocytes. The lymphocytes are the primary mechanism for containing HIV infection early in the course of the disease. Over time, telomere loss in these cells results in the gradual decline of their anti-HIV function, leading to clinical disease progression. Our hope is to use TAT0002 to prevent this immune decline and thereby prevent HIV progression.

Telomeres shorten with age; AIDS research would suggest that this shortening is occuring due to overuse. If your immune system is constantly set on high, the level of wear and tear leads this portion of your biochemistry to look and act like that of someone many decades your senior. If you can fix the first case, why not try the same methodologies for the second?

The more is known of human biochemistry, the more we'll see overlapping science between various fields. Research into manipulating telomeres to treat specific age-related conditions is increasingly active, for example.

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Towards Retinal Reconstitution

The MIT Technology Review reports on progress towards regenerative medicine for blindness: "Scientists are taking the first major step in using stem cells to replace retinal cells lost to degenerative eye diseases such as macular degeneration and retinitis pigmentosa. ... [researchers] can reliably make retinal cells from embryonic stem cells. The researchers are now implanting the cells into blind animals to see if the cells can restore vision. ... If we can replace the photoreceptors, we think we can restore vision. ... The researchers don't yet know if the cells can actually integrate into the complex circuitry of the eye to restore vision, but early results are promising. ... We should know within the next year if the cells can restore vision."

Link: http://www.technologyreview.com/printer_friendly_article.aspx?id=17307

TransVision 2006 Roundup

The TransVision 2006 conference - with the theme of "Emerging Technologies of Human Enhancement" - finished up this weekend in Helsinki. The worldwide transhumanist community provides a great deal of drive and material support to healthy life extension initiatives such as the Methuselah Foundation and MPrize for anti-aging research. As in any distributed collection of like-minded folk, there's a great deal more talk than action, but don't let that fool you into thinking that no action is taking place.

Video, discussion and reports from the event are making their way around the web. Here is a small selection of links:

Flicker photo set (including the obligatory appearance by biomedical gerontologist Aubrey de Grey in the local media)

Linking the real conference to a virtual space in Second Life

Many conference videos. Please do your part to take the bandwidth load off the organizer's servers; reformatting and posting to Google Video or YouTube would be very helpful.

Presentation materials from the various speakers. Aubrey de Grey's presentation is in the mix in both PDF and PowerPoint formats.

"I'm about as un-transhumanist as can be: I don't even want my nipples pierced. I wouldn't mind living longer though" - Chris Gray at HETHR

Conference community blog

Immortality Institute TransVision 2006 discussion thread

Quite interestingly, even though these people are mostly known in transhumanist circles, I was suprised about their considerable agreement that life extension is the most pressing and important issue at the moment and must be prioritized accordingly

...

I got interviewed by an Italian TV crew making documentary about the post-human condition. They said the documentary will probably have couple of million viewers. It will be aired in November, the program is called "C'ERA UNA VOLTA" which I have no idea what it means. The interviewer said the documentary will donwloadable from the tv-station website www.rai.it (the Italian equivalent of BBC, the specific channel is RAI 3) once it comes out.

...

We had quite the speculative fest with Aubrey [de Grey] about the reasons why big pharma companies have yet to take on the issue of anti aging despite the tremendous potential of making major cash and their obvious advantage on that area.

The last point is an interesting one; I believe it has much to do with the extent of regulation in medicine. The present structure and culture of regulation revolves around defining conditions and preventing anyone from commercializing products to do anything other than treat the results of those conditions. If you can't commercialize, there will be no funding for research and development. If there is no funding, no-one will mount challenges to the status quo.

In a system that actively discourages innovation and paradigm change, there will be little innovation or movement towards paradigm change. Sad but true. This is why practical medical technology lags far behind the cutting edge of what we know to be possible: our access to the best and newest technologies is being regulated to death at every level of the research and development cycle.

Unregulated industries advance at the pace of science. Did you know that venture funded companies are developing quantum computers already, for example? It was a matter of a few short years to run from working out the math, running the first experiments, and then right into business. That simply doesn't happen in medicine anymore. It could, but it doesn't, because pointless, useless, wasteful layers of government intervention ensure that everything is slow, expensive and of lower quality.

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Seeking Common Cancer Mechanisms

(From the LEF News). Perhaps the largest hurdle facing cancer researchers is the sheer diversity of cancer biochemistry. If age-related cancer was very complex but unvaried, scientists would already have a cure in hand. Thus, one aspect of cancer science is the search for controllable, common biochemistry across many different types of cancer: "CXCR4 is over-expressed in greater than 75% of cancers, including breast, ovarian, lung, colon, prostate, kidney, melanoma, brain, esophageal, and pancreatic - as well as numerous forms of leukemia, and childhood cancers such as acute lymphocytic leukemia and neuroblastoma. Northwest Biotherapeutics previously completed and reported on several preclinical studies using monoclonal antibodies to block CXCR4 receptor function, and reported significant inhibition of cancer cell proliferation, motility and invasion in multiple preclinical models both in vitro and in vivo."

Link: http://www.lef.org/news/LefDailyNews.htm?NewsID=4228&Section=DISEASE

Radical Life Extension Requires Faster Computers

If radical life extension is to get underway within our lifetimes, this era must become a golden age, a true revolution in biotechnology. This golden age of biotechnology requires the development of faster computers - much, much faster computers.

the hype that followed the complete mapping of the human genome in 2000 is true: The 21st century really is turning out to be the golden age of biotech.

All that gene-sequencing and protein-mapping is going to take us into a brave new world of health where you can walk into your doctor's office, have your DNA sequenced, find out what diseases you're at risk for, and then ingest a single chemical compound mapped to your proteins that will help eliminate your risk.

You can see that happening already, albeit in relatively small (and relatively pricey) ways.

...

Second, all that demand from biotech is going to boost our supercomputing power the same way the space race helped spur the development of the mainframe computers that were revolutionary for their time.

New branches of science that most of us are unfamiliar with are about to become household words, or at least recognizable job prospects: genomics (the study of genes), proteomics (the study of proteins), biostatistics and bioinformatics (which create algorithms to help analyze biological data).

Biotech research centers are springing up everywhere from Brazil to Zimbabwe. The field, awash in pharmaceutical cash, is sucking in researchers, programmers, engineers, biologists, computer scientists - anyone whose career path comes close to meeting the needs of computing-driven biotech.

The more that scientists examine the genome and pinpoint the locations of certain ailments, the more numbers that supercomputers will have to crunch to find a cure.

Consider that it is only in recent years, now that computing power per dollar has really started to take off, that major progress has been made in long-standing fields such as cancer research, genetics and immunology. Without advances in processing power, and the tools of bioinformatics built atop this foundation, scientists would have no hope of dealing effectively with the sheer complexity of human biochemistry.

With tools, understanding, hard work and funding we will be increasingly able to tackle the details of degenerative aging: replace failing mitochondria; turn cancer into a manageable, chronic condition; remove toxic byproducts that accumulate inside and around your cells with age; repair the aging immune system; build replacement tissue from our own stem cells; and much more. Every problem has an answer, if only the resources are applied to find it.

We are fortunately to live in a time in which the possibility exists to engineer additional healthy decades of life. Let's not miss this chance at a longer and much more fascinating future: we should do our utmost to support the advance of medical technology.

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Early Nanotechnology in Medicine

Diagnostics and pinpoint, per-cell drug delivery are the first applications of nanoscale engineering in medicine, as noted at Medical News Today. However mundane it might sound in comparison to plausible visions of future nanomedicine, steady infrastructure improvements are the real wheel of progress: "While the mortality rates of many cancers have decreased significantly in recent decades, the rate for ovarian cancer had not changed much in the last 50 years, primarily due to delays in diagnosis. By exploiting the unique properties of nanotechnology, we hope to detect ovarian cancer earlier using highly sensitive imaging tools and develop drug carriers that can deliver therapeutic agents inside tumor cells. ... We believe this 'small-particle' technology has the capability to quickly and sensitively detect cancer molecules earlier than ever before."

Link: http://www.medicalnewstoday.com/medicalnews.php?newsid=49682

Less Flexible Adult Brains, a Cause

Interesting longer-term possibilities arise from a knowledge of why adult brains cease to rewire themselves. From the Times Online: researchers "have identified a protein [PirB] that stops new neural connections forming in adult brains. ... brains of adult mice that lacked PirB retained the same rewiring ability of much younger brains. Without PirB to hold them back, the old mice were, in effect, able to learn new tricks. ... connections in the brain that form and rewire during childhood become more fixed later in life. This is why human beings are so versatile and receptive to learning earlier in life and become less flexible with age. Keeping connections fixed in the same place is normally an advantage, but after brain injury it would be helpful to have more flexibility. Being able to form new pathways might also allow adults to learn a new language, for example, with the facility of a child. ... By inhibiting the proteins that stop new connections growing, it may be possible for stroke victims to recover those missing links."

Link: http://www.timesonline.co.uk/printFriendly/0,,1-3-2319339-3,00.html

Exercise Already!

Via Scientific American, another small piece in the weight of evidence for the health benefits of exercise: "Our study shows that greater physical activity in your 30's, 40's, and 50's has beneficial effects well into the future ... Our results imply that a physically active lifestyle throughout the life course can not only lead to longer life expectancy, but can also help maintain our ability to walk and quality of life for a longer period of time in older adulthood ... seniors who reported engaging in vigorous physical activity during their earlier years scored nearly one point higher on a battery of tests evaluating their physical performance, including their walking and chair-rise speeds, than did those who reported the lowest level of physical activity. In a previous study, researchers found that older adults who experienced a one-point decline on the tests had an 80 percent increased risk of death." Taking better care of your health today means an increased chance of living to benefit from the working anti-aging medicine of tomorrow.

Link: http://www.sciam.com/article.cfm?articleID=80C94C09453DFE07681FDE78E769353F

Telomeres, Stem Cells, Aging

A paper in Nature touches on a most intriguing area of study: we know that telomeres tend to shorten and stem cells fail to replicate to repair tissue with increasing age, but what is the cart and what is the horse here? Do other modes of age-related cellular damage contribute to or result from these trends - to what degree and how? The science of aging is replete with questions of this ilk, as well as the strong sense that answers will come in the decade ahead. "[In some scenarios], the degree of telomere shortening can be correlated with disease duration, disease stage and severity as well as with response to disease-modifying treatment strategies. Whether increased telomere shortening represents a causal link between [hematopoietic stem cell (HSC)] turnover, replicative senescence and/or the induction of genetic instability in acquired HSC disorders remains to be shown. However, data from congenital disorders [suggest] that disturbed telomere maintenance may play a role for replicative exhaustion of the HSC pool in vivo."

Link: http://www.nature.com/leu/journal/vaop/ncurrent/abs/2404339a.html

The Alcor News Weblog

Cryonics provider Alcor has taken the eminently sensible step of starting up an official blog to better communicate with members, supporters, and the broader healthy life extension community:

For some time now, we have been looking for ways to bring more timely information about Alcor to our members and the public. The lead time for Cryonics magazine is several months, and even the email Alcor News only went out once per month. Furthermore, the email format was limited to short news items, which was often confusing. So, we decided to bite the bullet and join the blog bandwagon. As you can see from the dates on some of the posts, it took a while to work things out, but by doing this we hope to bring up items as they happen, with the space to do them more justice.

Equally sensibly, the folk at Alcor have started off with a few posts worth your time - such as a thought-provoking guest editorial on the future of cryonics. See what you think:

A friend of mine died this winter. He wasn't interested in cryonics, but what he didn't do is not the point of this essay. What he did do has saved uncounted lives, maybe including yours. The way this man went about his life has given me a clue to what I think is a major hidden problem with cryonics.

...

Cryonics, on the other hand, is in some ways still stuck in the 1960's. It's not popular and still looks like a cult to many people. So far it does not appear to be on its way to having a lasting effect on the world. A handful of people have labored mightily to bring forth a lot of suggestive evidence but not much proof that they can achieve what they plan. Why did EMS succeed while cryonics success has stalled?

Emergency Medical Services have not been around too much longer than cryonics, yet the idea of EMS quickly moved into the mainstream of American life. The most important reason is obvious -- EMTs, paramedics, ambulances, and trauma centers get immediate results. It doesn't take long to prove that the medical model saves more lives than the mortuary model. After 40 years of emergency work, EMS personnel can point to millions of rescued people, living witnesses to the success of the model. It is straightforward, easy to understand, easy to assimilate into your life. Yes, these people will still die anyway, just at older ages, unless technologies like cryonics can intervene. But cryonics has no rescued patients going on television talk shows to show that cryopreservation rescued them, and we won't have any such witnesses for decades at least. "Hey, guys, we can now preserve cells a whole lot better than we did last year," just doesn't have the same effect as living people telling how they were "miraculously" saved by the paramedics.

It is to all our betterment for the provision of cryonic suspension to grow and and succeed as an industry. If you are interested in living a far longer, healthier life, then you should also be interested in the most effective insurance policy against accident or the very real possibility of aging to death before the advent of meaningful anti-aging medical technology. Being vitrified with no great certainty of restoration is only the second worse thing that can happen to you; certain oblivion is worse, after all.

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Longevity Genes and Cancer

As reported by the New Scientist, work in lower animals continues to increase our understanding of the fundamental links between aging and cancer: "The authors speculate that signalling pathways that control longevity may have coevolved with tumour-suppressive mechanisms. ... Intuitively it all makes sense. We see this nice, clear genetic link between the longevity and tumour pathways. Presumably this is at least partially responsible for making cancer an age-related disease. ... C. elegans shares many tumour-related genes with mammals, including the ones investigated in this study ... It's one more element that makes you think that the aging genes that we discover and study in worms might be worth studying in vertebrates."

Link: http://www.newscientist.com/article/dn9777-longevity-genes-fight-cancer-at-its-source-.html

A Part of the Cost of Aging

The economic costs of age-related degeneration are staggering. Look at the numbers for just one small class of damaging events that occur after your body has accumulated a lifetime of unrepaired age-related damage: "Unless Americans do more to lower their risk of stroke and improve stroke care, the nation will pay $2.2 trillion over the next 45 years to care for people who suffer the most common form of stroke ... The $2.2 trillion estimate includes the cost of everything from ambulances and hospital stays to medications, nursing home care, at-home care and doctor's visits. They also include lost earnings for stroke survivors under age 65, based on current median salaries for each ethnic group. ... Stroke is the third-leading cause of death in the U.S. and a leading cause of serious disability. About 700,000 Americans suffer a stroke each year, and 157,000 of them die." When is it time to start fixing the root causes that lead to this and worse?

Link: http://www.sciencedaily.com/releases/2006/08/060817102406.htm

Longevity, Biochemistry and Genetics at The Scientist

The Scientist has published two interesting pieces on biochemistry, genetics and longevity as of today. The first provides more information, perspectives (and a brace of links to further resources) on the nematode longevity research noted at the Longevity Meme.

Long lifespan inhibits tumors:

Longevity mutations in C. elegans are unfriendly to tumor cells, contradicting research that's suggested the opposite effect

...

"With reduced growth factors, you'd expect reduced tumor growth," according to Wayne Van Voorhies from New Mexico State University in Las Cruces, who was not involved in the study. "The thing that was really surprising, though, was that it seems those daf-2 mutants have increased rates of apoptosis in the tumor cells," Van Voorhies said. "That's not an anticipated result."

The researchers found that apoptosis was upregulated in both normal and cancerous daf-2 cells, but decreased cell division was specific to tumor cells. "I was really surprised by that," Kenyon told The Scientist. "I expected to see [reduced cell division] in normal cells and we didn't."

You'll find all sorts of interesting things if you keep working away at a very complex environment with ever-better tools. Here we see more grist for the debate over what exactly determines relationships between cancer mechanisms and longevity in the biochemistry of various species. Continuing on, this same question is explored in commentary on another set of papers. These relate to research into the mechanisms of calorie restriction in mammals, centering around a small group of interacting genes and pathways:

Long Life and Forkhead Deacetylation:

The seemingly opposite results on gene expression suggested an intriguing mechanism: SIRT1 might urge FOXO-regulated processes away from death and towards survival. "It seemed that SIRT1 was providing a dream scenario for longevity," says Guarente, "whereby it was able to repress apoptosis while boosting DNA repair." But, complexity is never far behind a new pathway, and recent results suggest SIRT1 is quite pleiotropic and may even be an oncogene.

...

It all points to a balance, in that modulating SIRT1 could be good for longevity, but dangerous in terms of cancer risk. Experiments in mice, underway in a number of labs, should get at a big question of whether longevity and cancer can be uncoupled, says Brunet. But answers will take time, since mice live longer than yeast and worms. "It's another race," says Brunet, "just on a longer time scale."

It's always more complex than you think - and there is a compelling argument that this is the wrong direction for hopes of greatly increased longevity. There are many benefits to be had from a greater understanding of metabolic processes and the means by which calorie restriction increases healthy longevity and maximum life span - but this does not seem to the road to radical life extension. Could we reengineer human biochemistry to produce something more like whale longevity? Or would it be easier to work on fixing the known damage that causes aging?

My hat is in the latter court; I'm buying in on the argument that continually repairing the root causes of aging - thus reversing its progression - is easier than learning how to merely slow aging via metabolic, genetic and biochemical manipulations. Moreover, we seem to know more about how to get started.

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So Much Supporting Material for SENS

As pointed out at FuturePundit, so much of modern medical research acts to reinforce this message: the underlying logic of the Strategies for Engineered Negligible Senescence (SENS) is the best way forward to tackle age-related disease and frailty. Identify the damage that leads to problems, develop the means to fix it, then get in there and repair it early on, before it causes major problems; this is the utilitarian approach to any machinery, be it biological or otherwise. The present dominant paradigm for medical research and the treatment of age-related disease - patching up problems after the fact - is expensive and ultimately fails. If this patching was all we could do, then we should do it, and be glad we could make some difference to the health of millions. But it is not all we can do - so we must do better.

Link: http://www.futurepundit.com/archives/003652.html

Fast Forward Radio Interview With Aubrey de Grey

The folks over at the Speculist have posted the latest issue of Fast Forward Radio: an interview with biomedical gerontologist Aubrey de Grey, originator of the Strategies for Engineered Negligible Senescence (SENS) and advocate for vastly greater resources to be devoted to the rapid development of radical life extension and the defeat of degenerative aging.

Aubrey de Grey talked with us about SENS, The Methuselah Mouse Prize, and the SENS Challenge. We also get into why people try to make aging out to be a good thing and potential career options for the very long-lived. Plus, we look at the recent news that people seem to be living longer and healthier lives (which we commented about here) and how some have responded to these developments.

And if it's not too late to put in one more note about our recent blogiversary, here's the original Speculist interview with Aubrey from 2003.

Research relevant to SENS is taking place all round the world today, incidentally bringing us closer practical technologies capable of repairing some classes of age-related cellular and biochemical damage. Research explicitly under the SENS umbrella is just getting started, however: generous donors to the Methuselah Foundation have made possible the first steps in LysoSENS research. More is to come, but more funding is alwasys needed for projects of this ilk.

Read the outline for the proposed Institute for Biomedical Gerontology to see what de Grey would set underway with access to large-scale funding. This is the sort of vision we need to make real progress - and it's the sort of vision that is spurring other factions within the philanthropic and scientific communities into action.

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Exploring Cellular Self-Renewal

This truly is the barnstorming era of biotechnology; tools and capabilities of the past few years allow such a range of new experimentation that the unexpected turns up on a regular basis. Via EurekAlert!: "We can theoretically take a single brain cell out of a human being and - with just this one cell - generate enough brain cells to replace every cell of the donor's brain and conceivably those of 50 million other people. ... This is a completely new source of human brain cells that can potentially be used to fight Parkinson's disease, Alzheimer's disease, stroke and a host of other brain disorders. It would probably only take months to get enough material for a human transplant operation. ... The findings document for the first time the ability of common human brain cells to morph into different cell types, a previously unknown characteristic, and are the result of the research team's long-term investigations of adult human stem cells and rodent embryonic stem cells."

Link: http://www.eurekalert.org/pub_releases/2006-08/uof-hpd081606.php

Discussing the Strategies for Engineered Negligible Senescence (SENS)

If you are interested in learning more about the Strategies for Engineered Negligible Senescence (SENS), as well as debating its merits with knowledgeable folk, I recommend a visit to the SENS forum hosted by the Immortality Institute.

Supporters of the SENS proposals and overlapping efforts - such as the LysoSENS research and MPrize for anti-aging research organized by the Methuselah Foundation - have quite different views on the future and emphasis of areas within SENS, not to mention the ethics that come with it. The ethos of full steam ahead to radical life extension is not a big tent position yet (you have to be much more moderate to obtain big tent status in 2006, sad to say), but it's big enough to shelter a number of very interesting debates and challenges. For example:

Jump right on in - it's fascinating stuff, and very accessible to the interested layperson.

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Closing On An Early Alzheimer's Test

Scientists have been working towards a non-invasive test to detect Alzheimer's disease as early as possible for a few years now. It seems they're almost there: researchers "describe a biomarker that can accurately distinguish between Alzheimer's disease and other forms of dementia during the first one to two years of the disease's progression. The BRNI biomarker showed high accuracy when tested with human skin cells from a tissue bank, as well as for samples obtained in a previous, unpublished study of patients with autopsy-confirmed diagnoses. ... Many scientists have concluded in recent years that Alzheimer's effects are found throughout the body, not just in the brain. By testing for signs of Alzheimer's-related inflammation in skin cells called fibroblasts, the BRNI team has located a biomarker for the disease that can be tested without the invasive tests previously required." As for all failing machinery, early discovery of problems means that more can be done for greater benefit and at less cost.

Link: http://www.newswise.com/articles/view/522652/

Thoughts On Radical Life Extension

You'll see more transhumanist and pro-healthy life extension thinking in the press as those ideas with the most merit are discussed more widely. This via the Naples Sun Times: "Who wants to live forever? I certainly do, but I am constantly amazed by meeting people who don't. ... It doesn't have to be that way any more. Once a science-fiction staple, immortality is another fantastic notion about to become a reality. ... The era of life extension has already begun. We won't have to cheat the Reaper. We'll be able to beat him fair and square. ... If this all seems too fantastic, that's because we all have deep-seated opinions about life and death." I disagree with the assessment of timeframes in this article - that we will die as the last mortal generation, forced to employ the ultimate insurance policy that is cryonics technology. In a world in which widespread support can see a major medical research infrastructure built in a decade, we can do better than that.

Link: http://www.zwire.com/site/news.cfm?newsid=17056590

Help the Calorie Restriction Society Raise Research Funding

Active members of the Calorie Restriction Society have had a positive influence on the degree and direction of calorie restriction (CR) research in humans for a number of years now, helping scientists who have demonstrated that fewer calories mean less age-related disease and quite probably more healthy life. As is true of many of the best patient advocate and pro-research advocacy groups, the Calorie Restriction Society has close ties with the scientific community; members have stepped up to the plate to help human studies happen more rapidly. You can find links to a number of more recent results at the Longevity Meme, including these:

Now the society is stepping up again, this time to raise funding for further CR research. This initiative will build upon existing relationships with talented, well known scientists to correlate gene expression and cell signaling indicators in human calorie restriction practitioners to clinical markers of health and aging. In essence, this work will continue to raise the bar in proving beyond a doubt that CR in humans is very beneficial to healthy longevity. You can find more information about the researchers in a PDF format release at the society website:

Luigi Fontana, M.D., Ph.D.

A key aspect of this new CR study will be to build on the CR study reported by Dr. Fontana in 2004, thus establishing a longitudinal aspect to the evaluation and adding many further tests. The major objective of the proposed research is to determine whether long-term CR with adequate nutrition results in some of the same metabolic, hormonal and gene expression changes in humans that have been shown to be made by CR in rodents.

This study may also help to characterize in humans new markers of aging and longevity that can help physicians contribute to the prediction of mortality and morbidity of the general population.

Dr. Fontana says, "It is the hope of those of us studying CR that, once its mechanisms of action are understood, it will be possible to mimic the effects of CR on aging using less drastic interventions."

Stephen Spindler, Ph.D.

One of his great contributions to aging science is the genetic profiling of calorie restriction effects on animals. Dr. Spindler in one of his famous CR studies ("Use of microarray biomarkers to identify longevity Therapeutics," Aging Cell, 2006. PMID: 16441842) writes, "CR acts rapidly, even in late adulthood, to begin to extend life- and health-span in mice. We have linked these effects with rapid changes in the levels of specific gene transcripts in the liver and the heart. Our results are consistent with the rapid effects of caloric intake on the lifespan and/or biochemistry and physiology of Drosophila, rodents, rhesus macaques and humans."

Building on years of work on animals, Dr. Spindler and his lab will provide insights into how calorie restriction affects genetic expression in calorie-restricted humans.

Shin-Ichiro Imai, M.D., Ph.D.

Shin Imai joins the study to focus on the function of mammalian Sir2 NAD-dependent deacetylase. Dr. Imai writes: Sir2 has been demonstrated to play key roles in regulating aging and longevity in lower eukaryotes and also implicated as a mediator for caloric restriction, which retards aging and extends life in variety of organisms.

To move forward with the work, Calorie Restriction Society activists are seeking to raise $230,000 in donations. You can help support this work:

We need to raise $230,000 to make this project happen. This means we need contributions large and small. Make an investment that is priceless and learn more about slowing aging - what works and what doesn't. Please send your donation directly to the Society Treasurer,

David R. Stern
7223 S Rt 83 #142
Willowbrook, IL 60527

Or to

Bob Cavanaugh at the Calorie Restriction Society
187 Ocean Drive
Newport, NC 28570

or donate online using a Credit Card.

For other payment options, please contact The Calorie Restriction Society by phone at:

914-923-1605 or toll-free at 866-894-1812

The Calorie Restriction Society is a tax-exempt organization under Section 501(c)(3) of the IRS Code. Contributions are fully tax deductible.

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Overlapping Cancer, Stem Cell Research

From UCSF Today, an introduction to the way in which cancer research and stem cell research now overlap. "While several researchers are investigating the likelihood that some tumors get their stem cell characteristics from stem cells themselves, others are looking into the possibility that cancer stem cells might acquire their characteristics another way. Scientists are investigating whether progenitor or even fully differentiated cells somehow shirk assigned roles, de-differentiate and acquire stem-cell-like potency en route to becoming cancerous." We can hope that overlapping biochemistry at the cellular level becomes the key to faster progress in these very complex fields - that the cancer research establishment will contribute as much to the advance of stem cell based regenerative medicine (and knowledge of aging) as it does to defeating cancer ... and vice versa.

Link: http://pub.ucsf.edu/today/cache/feature/200608117.html

Learning From Leprosy

There is no such thing as useless knowledge in biochemistry; at a fundamental level, all new learning leads to applications in medicine. For example: "Glial cells - nervous system cells that form a highly specialized insulating sheath called myelin that surrounds nerve fibers - under certain conditions can 'de-differentiate,' re-enter the cell cycle and revert to an unspecialized state, from which they can repair damaged tissues. Scientists are eager to learn how glial cells accomplish this trick, as it could teach them not only about neurodegenerative diseases, but also have implications for regenerative medicine. Now, using leprosy bacteria, laboratory primary cultures of human and rat glial cells and genetically engineered mice, [researchers have] uncovered new molecular pathways that lead to demyelination - the breakdown of the myelin sheath - as well as de-differentiation and cell proliferation of mature Schwann cells, the glial cells of the peripheral nervous system."

Link: http://newswire.rockefeller.edu/?page=engine&id=519

Aging is a Terrible, Disabling Disease That Kills You

Aging is a terrible, disabling disease that kills you. I have it, you have it, we all have it. Unless we band together to do something about it, we all will suffer and die. This banding together faces a large obstacle, however: most people, for one reason or another, don't think of aging this way, even though the facts are very much in evidence.

Anne C. advances this point more succinctly than I:

Think about it for a moment: if I described the physical signs and eventual prognosis of aging to you, but you didn't know how old the person was that I was talking about, would you seriously consider the condition to be something nobody should look into addressing medically? Aging takes a healthy, vigorous person and saddles them with progressively increasing susceptibility to cancer, heart disease, diabetes, stroke, joint problems, overall weakness, and immune dysfunction and eventually kills that person. Without fail.

When we see these symptoms in children, we call it progeria, and you'd be hard-pressed to find anyone suggesting that we should just "let nature take its course" and let these children get sicker and sicker to the point where they die. Quite rightfully, we attempt to address their health challenges with therapies like aspirin, blood pressure pills, and cholesterol-lowering drugs. In addition to these conventional treatments, we also perform research along possible avenues that might eventually enable more effective treatments that strike right at the source of this condition -- the genes and underlying biology.

Even when these symptoms start appearing in younger adults -- a sort of "late-onset progeria" is diagnosed, called Werner syndrome. This condition results in the initial appearance of rapid physical aging following puberty. Individuals with Werner syndrome commonly die in their forties or fifties.

Notice anything interesting about the Werner prognosis? Though the expected lifespan of an individual afflicted with Werner syndrome is actually comparable to the average lifespan just over a century ago, this condition is most assuredly considered something that an individual would want to fight against with all available medical resources.

Why then, does there exist a form of willful communal blindness to the terrible, widespread disease that is aging? Why is there no widespread, organized urgency to do something about it? Compare this state of affairs with attitudes towards equally horrific medical conditions that afflict far fewer people. Small scientific armies - and commensurate funding - have been raised and directed to cure cancer, AIDS, Alzheimer's, malaria, diabetes, Parkinson's and many other conditions. But aging, the condition we all suffer and die from, the source of so many other conditions we name and fight, is largely ignored or accepted.

My thought for the day is this: is the human drive for common ground so strong that any horrid unpleasantness shared by all is rendered acceptable? Is it the case that stubborn resistance to change will kick in no matter how beneficial change might be? We are moving from an era in which nothing could be done to defeat aging into an era in which advancing biotechnology will give us the tools to do just this. All the old attitudes are no longer relevant, and have in fact become quite harmful:

You become stressed, sick and crazy if continually focused on matters you cannot change - and so evolution has led to humans who are very skilled at avoiding this sort of result. People being people, simple rationales became vast, complex, overwhelming cultural edifices over the generations. Now, at the dawn of the biotechnology era, the inevitable is no longer inevitable. The research establishment - if sufficiently funded and motivated - could make meaningful inroads into repairing and preventing the root causes of aging within our lifetime. The leftover cultural and hardwired human habits relating to our decay and mortality now actively hinder progress towards the elimination of age-related degeneration, disease, frailty and death.

A parable for this most important transformation of our time has already been written. It's called "The Fable of the Dragon-Tyrant", and recounts the passage we would like to see: from ignorance and acceptance of the daily toll of aging, through the struggle with ourselves to find the will to seek a cure, to the final defeat of age-related death and suffering. Go now and read it.

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Looking at the Enemy

The Mayo Clinic provides a somewhat whitewashed, clinical guide to the degeneration of "normal aging." This is a part of what we fight to prevent by supporting the development of a meaningful anti-aging research infrastructure and community - this and more than 100,000 deaths every day. Experiencing these degenerations is much more of a horror - living in a failing body is anything but clinical. Yet matters are improving: "The longest documented human life span is 122 years. Though a life span that long is rare, improvements in medicine, science and technology during the last century have helped more people live longer, healthier lives. If you were born in the early 1900s in the United States, your life expectancy was only about 50 years. Today it's around 77." Improvement can continue, and will move faster in the future - but only if we all help to make it happen.

Link: http://www.mayoclinic.com/health/aging/HA00040

Life Span in Bees

An article from The Age notes research into the biochemistry of bee life spans: "The common worker bee lives just six weeks, but if the same egg was raised as a queen bee, the queen can live for up to six years. La Trobe University's David Vaux is a specialist in apoptosis, the science of how cells die. His research aims to unlock the answers to the queen bee's 50-fold increased lifespan. ... the only actively dividing or replicating cells in queen bees were the ovaries, suggesting that all the other cells in the queen were long-lived. The finding suggested that queen bees possess a cellular maintenance system that is not switched on in the worker bees." Greater repair of cellular damage should lead to longer life spans; the final results will no doubt be interesting, but most likely not directly relevant to human longevity. Researchers have learned a great deal about aging from flies and yeast, however, so we shall see.

Link: http://www.theage.com.au/news/national/an-ageold-question-will-wax-slow-wane/2006/08/13/1155407670358.html

What is the Significance of Recent Pluripotency Research?

As I'm sure you're aware, given the widespread coverage, Japanese scientists may have found the keys to turning adult cells into pluripotent embryonic stem cells. Their initial tests are pretty convincing for a first run out of the gate:

The researchers found that four of those factors, known as Oct3/4, Sox2, c-Myc, and Klf4, could lend differentiated fibroblast cells taken from embryonic or adult mice the pluripotency normally reserved for embryonic stem cells.

They further reported that transplantation of the [induced pluripotent stem cells (iPS cells)] under the skin of mice resulted in tumors containing a variety of tissues representing the three primary types found in mammalian embryos. Those primary "germ layers" in embryos eventually give rise to all an animal's tissues and organs.

Following injection into blastocysts, iPS cells also contributed to mouse embryonic development.

Looking back a little, you might recall that Oct4 and Sox2 have already been used to prevent differentiation and keep embryonic stem cells pluripotent. Still, there is a certain amount of skepticism in the worldwide audience:

Personally, I'm skeptical of the claim that reprogramming -- a long sought-after mechanism that would sidestep ethical issues surrounding embryonic cells -- requires such simple steps. Only further experiments will reveal whether four factors are all you need to dive into reprogramming with full gusto.

And more:

There are still a lot of unknowns: are the cells truly pluripotent, or do they have some limits on their development that have not yet been identified? What is the risk of abnormal development, mutation, or cancer with these cells? Do human cells use the same proteins? Can cells other than fibroblasts be induced into pluripotency with some or all of these factors? Nevertheless, I think this is an important finding and one that needs to be pursued aggressively.

This attitude is justified, I think. If there is anything we all know for sure about biochemistry, it is that it is always more complex than you think. We sometimes get lucky, however, and find an important mechanism to be relatively simple - as was the case for progeria, for example. The odds are against that being true here, but you never know.

It seems to me far more likely that iPS cells have been induced into a state strikingly similar to that of embryonic cells, but different in some important way that will come to light later. I'd be willing to lay odds on issues relating to development, cancer and aging, areas that overlap considerably in terms of cellular biochemistry and genetics. We shall see, and probably very soon. This is the sort of research that will inspire many groups to forge ahead at full steam.

Randall Parker notes:

If this approach works for humans as well then some day we'll be able to have pluripotent stem cells made from our own cells. Then those cells could be used to grow replacement parts such as internal organs or injected into joints to supply joint material to those suffering from arthritis.

The researchers chose factors to introduce into adult cells by looking at which genes are turned on in embryonic stem cells. Note that advances in biotechnology in recent years have made it a lot easier to measure the levels of activity of many genes at once.

...

The researchers still need to repeat this experiment with human cells to find out if this method will work for human cells as well. If they succeed then this discovery could open the gates for much higher levels of research funding for pluripotent stem cells.

I predict that repeating - and expanding upon - the same work for human cells won't take very long. After that it'll be a longer and more interesting road, but I shouldn't need to elaborate greatly on the enormous benefits that can - and will - can be derived from a low-cost, readily available source of patient-matched pluripotent cells. This is a gateway into an era of expansive, impressively effective regenerative medicine for all forms of damaged tissue.

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Partial Immortalization

I seem to recall noting that we stand at something of a brand inflection for the future of healthy life extension. The old brands ("life extension", "anti-aging") are losing their strength or merits, and new labels have not yet arisen to prominence. So everyone picks their own, which is fine - let cultural evolution sort out the winners. If the Methuselah Foundation keeps up the good work, it'll be SENS all the way. In this context, I thought I would point you to a book and blog in slow progress - "Partial Immortalization: Regenerative medicine and its consequences". As for so many of these things, I suspect that the footprints left on the journey will prove more valuable than the initially selected destination. The more that people talk sensibly about the advance of healthy life extension medicine, the better. This broad conversation - in media of all sorts, multiple threads running, splitting and crossing all the time - is a necessary precursor to an environment more supportive of research funding.

Link: http://pimm.wordpress.com/

Stress and Telomeres Again

Scientists have been exploring links between the biochemistry of stress and more rapidly shortened telomeres for a couple of years now. Here's more from Forbes: "We examined healthy women and found that psychological stress was related to [shortened telomeres]. As a result, the immune system of the stressed-out women is apparently aging at a faster rate. The treatments for this problem are what you might expect. 'Everything we already know about fighting off chronic disease, like getting sufficient sleep, staying active throughout life, and having a healthy diet' may stave off premature aging of the immune system." Shortened telomeres are linked to a number of age-related conditions. Stress is clearly a system-altering phenomenon for the human body, so the hypothesis here is plausible - but correlation is not causation. From where I stand, more delving into the mechanisms is needed to demonstrate that the stress response is acting as a significant source of life-shortening cellular damage.

Link: http://www.forbes.com/forbeslife/health/feeds/hscout/2006/08/11/hscout534367.html

Calories, SIRT1 and Alzheimer's

ScienCentral follows up on research into calorie restriction and neurodegeneration: "Calorie-restriction - consuming 30-percent fewer calories than normal - is the only scientifically proven way to slow the process of aging in organisms ranging from yeast to mammals. Now a new study in mice shows that through a similar mechanism, calorie restriction may also slow or prevent Alzheimer's disease. ... With this kind of calorie restriction we were able to improve memory function - I would say five-fold times more efficient ... Excitingly, we have been able to demonstrate that just the SIRT1 molecule, once re-introduced into brain cells was capable to recapitulate almost the same identical features of calorie restriction ... Through the regulation of SIRT1, we might be in a position to cure the disease."

Link: http://www.sciencentral.com/articles/view.php3?type=article&article_id=218392836

Living Well to 100 Conference

The second Living Well to 100 conference will be held in Boston in November of this year: "We have brought together an outstanding group of experts to explore the theme, 'Is Inflammation Central to Aging?' As with the first Living Well to 100 Conference, we will focus on wellness and how to keep healthy people well for a greater portion of their lives. Among the topics to be addressed include how to identify which individuals may benefit from reducing inflammation, what key molecular targets may be mediating the role of inflammation in specific diseases, and how lifestyle and nutritional factors may modulate inflammation. The discussions will also consider the potential role of inflammation during different stages of the lifecycle."

Link: http://www.wellnessto100.org/

A Brace of Research Via EurekAlert!

EurekAlert! is packing in the interesting releases today, starting with more on recent research into the age-related decline of mechanisms that clear out the protein aggregates associated with neurodegeneration. Take a look:

Scientists discover age-regulated cellular activities that protect against protein aggregation:

Now, we want to use this mechanistic information to discover the macromolecular basis for these activities and to discover small molecules that will delay the aging program and thus delay the onset of proteotoxicity associated with these diseases by modulating aggregation and disaggregation activities. The hope is that, by manipulating the protective mechanism inherent in cells, we can find a single entity - a single drug - that would be useful for a variety of neurodegenerative diseases where protein aggregation leads to neurodegeneration.

That is a hopeful destination for any research: to uncover sufficent simplicity in the midst of complex biochemistry to build a cost-effective intervention that has widespread utility.

Wear and tear of stress: the psychoneurobiology of aging:

Cumulative stress effects, said McEwen, are showing up in people who are under constant stress, like those in caregiver situations or those who suffer from obesity and/or diabetes. These people are more likely to have decreased telomerase activity. Telomeres are enzymes that regulate how many times an individual cell can divide. Telomeric sequences shorten each time the DNA replicates, which is a process that happens prior to cells dividing. When at least some of the telomeres reach a critically short length, the cell stops dividing and ages (senesces) which may cause or contribute to some age-related diseases.

...

In another review of the current literature on the interactions of the brain, stress and the endocrine system, more evidence shows how cumulative stress and the occurrence of disease may define age more than chronological aging. According to the review, certain diseases start to occur when the anabolic hormone levels start to decrease - when the tissue builders like growth hormones, testosterone, estrogen and thyroid functions start to drop off and when the catabolic hormones start to increase. These hormones, the tissue fuelers, can become too active and actually break the body down. Cortisol - a stress hormone - can become more reactive when responding to acute challenges as one gets older.

This one seems to me to be a good example of people who have a portion of the entire picture to hand, but aren't quite getting the full view - or are applying their incomplete knowledge as a way of explaining the whole problem. Give someone a hammer and everything will be treated as a nail until proven otherwise. Chronic stress is clearly not good for you, but the vital, missing part of the picture here is the accumulation of cellular damage through many other causes.

Exercise helps sustain mental activity as we age, may prevent dementia-like illnesses:

From this review we have found that physical and aerobic exercise training can lower the risk for developing some undesirable age-related changes in cognitive and brain functions, and also help the brain maintain its plasticity - ability to cover one function if another starts failing later in life.

Exercise is very good for you. There's nothing out there today that beats out the proven beneficial effects of moderate exercise combined with calorie restriction for most folk. Take better care of your health, and you'll live a longer life - not to mention increasing your chances of living into an era of real, working anti-aging medicine.

New method shows that neocortical nerve cells are not renewed:

Most bodily organs continually die and regrow a little at a time. It takes two years, for example, for all the cells of the liver to be replaced by fresh ones. Research from Karolinska Institutet in Sweden now shows that there is one important exception to this - the nerve cells of the brain remain the same throughout a person's life.

Many scientists have suspected that the cerebral nerve cells lack this renewal ability. However, studies on apes and rodents have indicated that brain cells can reform in mammals after all - including man. One problem with these findings has been the research methodology, as the most common way of measuring the age of nerve cells is extremely complicated, especially in man, and gives unreliable and controversial results.

You might other past articles on the art and science of pinning an age on different cell populations in the body. It seems the back and forth as to whether we grow new neurons or not is heading back to its original position after some years of results indicating we do. Advances in biotechnology will likely render this all moot - researchers are already closing in on the first therapies that will grow new neurons for therapeutic purposes.

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Research to Repair Aging: Where is the Urgency?

A great improvement in mainstream scientific culture has recently come to pass. Thanks to the tireless work of scientist-advocates, it is now acceptable to discuss the application of science to extending the healthy human life span.

This is a sea change from even a decade ago, when scientific anti-aging research was the instant-death third rail of grantsmanship. If you liked working as a scientist, you didn't talk about the defeat of aging, no matter how obviously relevant your work was to the end goal of extending healthy longevity.

These cultural changes should bring more support for necessary improvements in the approach to dealing with age-related frailty and degeneration. More progress could be made by redirecting resources away from the wasteful find-and-patch approach - plugging holes in the crumbling dam and hoping for the best - and towards the more efficient method of dealing with root causes in advance of resulting problems.

The present day mainstream approach to age-related degeneration, disease and frailty is a function and outgrowth of a historical lack of knowledge; if you don't know why the dam is crumbling, you get to plugging the holes and damn the expense. When plugging the holes is all you can do, then it's all you can do - it'll cost the moon and the dam will collapse only a little later than it would otherwise have done.

We can do better than this. Not right now, but soon.

The "plugging the holes" methodology is part and parcel of old school gerontology, moving hand in hand with the goal of compression of morbidity. Improve late life health, but don't extend life, in other words. Fortunately, this may be impossible - but the sooner people are working with better aims, the better.

Researchers who aim at a compression of morbidity are seeking to reduce or even eliminate late life frailty, disease and incapacity - but with no expectation of extending healthy life span. The framing principles of the reliability theory of aging and longevity, amongst other work, would seem to suggest that this is impossible - that any successful efforts to alleviate age-related suffering will also extend healthy life span.

In this viewpoint, all manifestations of aging - disease, frailty, degeneration and death - are manifestations of accumulated damage. The best way to prevent age-related degeneration is to prevent or repair that damage, but this will also extend healthy life span. You can't have one without the other - and a good thing too!

Which brings us to the urgency, or rather lack of same. I think this is a fairly typical quote from recent research widely reported in the mainstream media:

The finding that genetics, lifestyle decision making, and their interactions, may influence the ability to reach old age with preserved cognition is exciting. Identifying such genetic and behavioral factors may hold promise for better understanding the aging process and perhaps one day enriching or extending the lives of other individuals.

Perhaps, one day. Bah. We can do better, but only if we challenge ourselves and set goals.

I see driving urgency - of the sort seen in the AIDS, Alzheimer's and cancer research communities - as the next phase of cultural change in the scientific community. Driving urgency means a recognition that while there is always more left to understand, enough is known to produce working technology and a real impact upon the problem at hand. Once it is acceptable to discuss progress towards preventing 100,000 deaths every day and the concurrent suffering of hundreds of millions, I think this urgency to bring working anti-aging medicine to the table will naturally follow.

Not so naturally that we advocates can sit back and watch, but it will come. We'll make sure of that.

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Engineering Pluripotency

Scientists continue to make progress towards reverse-engineering the workings of our cells. At some point, they will understand how to make a pluripotent cell from any cell; this will make a great many avenues of research and regenerative medicine much easier. From EurekAlert!: "With the introduction of just four factors, researchers have successfully induced differentiated cells taken from mouse embryos or adult mice to behave like embryonic stem cells. ... The [cells] exhibit the physical, growth, and genetic characteristics typical of embryonic stem cells ... We have demonstrated that pluripotent stem cells can be directly generated from fibroblast cultures by the addition of only a few defined factors ... Fibroblasts make up structural fibers found in connective tissue. ... The finding is an important step in controlling pluripotency, which may eventually allow the creation of pluripotent cells directly from somatic cells of patients."

Link: http://www.eurekalert.org/pub_releases/2006-08/cp-wff080906.php

The Roots of Neurodegeneration

(Via EurekAlert!) The rate of production and clearance of amyloid beta in the brain is actually very rapid. Excess amyloid increasingly seems to be a problem of clearing mechanisms: "Aging is the most important risk factor for neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and Huntington's disease ... the age onset of these diseases is not simply a matter of time but that the aging process plays an active role in controlling the onset of toxicity ... Half of all people who reach age 85 will likely be affected by Alzheimer's disease, and the onset age - usually around 75 - is almost the same for all sporadic neurodegenerative aggregation diseases. ... Throughout life, brain cells produce aggregation-prone beta-amyloid fragments that must be cleared. ... This process is very efficient when we are young but as we get older it gets progressively less efficient ... In individuals who carry early onset Alzheimer's-linked mutation, an increased 'aggregation challenge' leads to clearance failure and the emergence of Alzheimer's much earlier."

Link: http://www.eurekalert.org/pub_releases/2006-08/si-nrp080706.php

The Right Attitude to the Future

Eric Boyd has the right idea about healthy life extension, the future and our attitudes towards both: "the purpose of a goal isn't to achieve what it states, it's to motivate you to work at it in the now. ... A good example of that is longevity - in theory, it's just extra years beyond age 75 or so, and therefore not important to me for another (75-28=) 47 years. But in practice, the implications extend right back to things I should be doing now. The most obvious is, I need to be in good health in order to benefit from extra years of longevity treatment development, because it would be a huge shame to be just on the wrong side of the 'escape velocity' point." In other words, you have the power to shape your future - and we can collaborate to build a better future for all of us, starting with the development of healthy life extension technologies and moving on to the defeat of aging.

Link: http://digitalcrusader.ca/archives/2006/08/the_real_purpos.html

A Reminder On Views and Expertise

Via The Age, a reminder that scientists aren't immune to lack of foresight, imagination and specific knowledge outside their domain: "This is complete nonsense, breathtakingly arrogant and breathtakingly ignorant. To extend human lifespan you would need to completely re-engineer the body, which took evolution millions of years to create, and that would result in a completely different being. ... He said mammals have a limited natural life span that is unlikely to change." I'll live with the fact that some folk think it's arrogant to work to defeat aging and thus save more than 100,000 lives every day. Their own lives are made poor by their attitudes. But proposals for engineering the human body for a longer, healthier life are already on the table and well-debated in scientific circles. The discussion is now a matter of "how much more healthy life, and how soon." Those who do not acknowledge this fact are simply out of touch - and perhaps out of their depth.

Link: http://www.theage.com.au/news/National/Geneticists-slams-antiageing-movement/2006/08/09/1154802945088.html

Stem Cell Therapies Under Trial in Thailand and the UK

Even a brief glance at a site like ClinicalTrials.gov shows that a great deal of stem cell work is presently moving into the trial stage in the US. I thought I'd point out studies in Thailand and the UK today, however, since both have been in the mainstream media recently. As I've mentioned in the past, groups in Thailand are engaged in building an effective research and development infrastructure, attracting cutting edge work away from death by regulation in the US and Europe. This article points out continued progress:

The project seeks to help victims of Parkinson's disease, spinal cord injury and strokes, and transplanting of developed stem cells into patients' central nervous systems is expected to begin this year

...

"[Don't hold your breath], we're just at the beginning," said neurosurgeon Smarn Tangaroosin of the Prasat Neurological Institute. "Though the efficacy of stem-cell transplant remains uncertain, it's proved to be safe so far."

The Prasat team is still undecided whether to use embryonic or adult stem cells, both of which have pros and cons that need to be weighed very carefully, Smarm said.

...

[With Parkinson's] we're determining whether to grow dopaminergic neurons [nerve cells] outside and then inject them into the patient's bodies, or inject premature cells and then programme them to become the proper nerve cells later

Meanwhile, scientists in the UK are making progress with bone regeneration using adult stem cells that is on a par with the state of the art in heart tissue regeneration. From the BBC:

It involves taking stem cells from the patient's bone marrow, stimulating them in a laboratory, then implanting them back into her leg.

The stem cells help to grow new bone and knit the fracture site together.

...

These patients have already had several operations on fractures that haven't healed over several years and are facing amputation or a lifetime of pain and disability.

Having just completed the tenth stem cell implant, the initial results are extremely encouraging. In fact, three of our patients have already handed back their crutches.

The therapies derived from this technology base will only become more impressive and effective in the years ahead. In the 2020s we will look back and wonder how people survived without access to a general purpose repair kit for damaged and diseased tissue. The answer being, of course, that all too often they don't - we should all be glad that a wide range of horrible, fatal injuries and age-related conditions will soon vanish from common view.

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Defeating Immune Rejection

As noted by the Life Extension Foundation News, research into xenotransplantation continues to advance in parallel to regenerative medicine and tissue engineering work. That's not the important part of this research however - the significance is all in what was done to suppress the normal difficulties with immune rejection: "MicroIslet says it has developed a way to encapsulate cells taken from pigs in a material so that it is not recognized by the body as foreign material and then attacked by the immune system. The transplant recipients were seven rhesus monkeys whose own pancreatic islets (clusters of endocrine cells that contain the cells that produce insulin) were destroyed. ... If there's evidence that rejection is not occurring, despite no immune suppression, that's promising and potentially important for the future." Very much so - a wealth of opportunities lie in the future for any successful variant of this technology.

Link: http://www.lef.org/news/LefDailyNews.htm?NewsID=4179&Section=DISEASE

Better Commentary on Mitochondria, Evolution and Longevity

I briefly noted a recent paper on evolution, mitochondrial biochemistry and longevity at the Longevity Meme a little while ago. I suggested, rather tersely, the possibility that longevity was not in fact directly selected, but rather was a pleasant side effect of other evolutionary pressures on mammalian biochemistry. The commentary at Ouroboros is of a much higher quality, needless to say:

The point toward which I am laboring is this: If we are to use correlative studies as a guide to instruct future mechanistic studies, it's best to know which variables are the strongest correlates of one another, and which are merely piggybacking. In this case, since maximum lifespan is concealed from selection in the wild, one might lean toward a model in which mitochondrial proteins co-evolved with the metabolic demands of body size, with lifespan changes as a spandrel - in contrast to the author's model, in which lifespan is the driving force of mitochondrial evolution.

These objections fall short of pistols-at-noon disagreement with either the model, prediction or conclusions of this paper, and I raise them to provoke discussion rather than to criticize the work before us. The paper is a step toward addressing a major issue at the interface of evolutionary and oxidative theories of aging, and it is left to the field as a whole to evaluate its conclusions and decide where to place the next foot.

A number of starting points for a comparatively gentle introduction to evolutionary theories of aging and longevity can be found back in the Fight Aging! archives. You might begin with these:

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Geron's Stem Cell Research

The MIT Technology Review looks at a portion of Geron's stem cell research: "Geron's clinical trial of a therapy to treat spinal cord injuries will likely be the first human test of an embryonic stem cell-based treatment. ... embryonic stem cells are the starting ingredient rather than the treatment itself. The embryonic stem cells, which are potentially able to form any human cell type, are transformed into oligodendrocytes - a type of brain cell that wraps itself around neurons, forming a fatty insulation layer that allows electrical messages to be conducted throughout the nervous system. These cells are then injected into the site of the injury, coating neuronal projections that were damaged in the accident and restoring communication to the nervous system."

Link: http://www.technologyreview.com/printer_friendly_article.aspx?id=17256

More On the TOR Gene

EurekAlert! provides more information on the role of the TOR gene in that fascinating intersection of metabolism, calorie restriction, longevity and health: "flies with the mutated form of TOR had longer life spans than control flies. ... Our study adds another dimension to TOR's activity by revealing unexpected and novel levels of beneficial regulation of insulin metabolism, by reducing insulin resistance. This study provides the first details of how TOR may regulate energy homeostasis and responses to aging, in particular the coordination of weight reduction effects caused by caloric restriction and, in humans, it may explain the effects of the Atkins diet. It suggests that reducing TOR function could lead to a possible treatment for any or all symptoms of metabolic syndrome and insulin resistance. ... reducing TOR function also blocks the age-dependent decline of heart function, providing a partial explanation for why excess calories from overeating can lead to resistance to insulin's ability to process sugars and may contribute to reduced heart function."

Link: http://www.eurekalert.org/pub_releases/2006-08/bi-ipc080206.php

Regenerative Medicine For Deafness

More attention is being given to research into regenerating the mechanisms of hearing that go awry in some forms of deafness. Via CNN: "stem cells have the capacity to regenerate in the inner ear. The stem cells are especially good at growing into the microscopic hair cells that make hearing possible. ... It's like a little microphone in your ear, and when the microphones go bad, then you don't hear anymore. We can grow these tiny microphones from these stem cells ... I hope that in five years, we are at a point that we can say that it is possible to cure deafness, at least in an animal. That will be the first step toward treating human patients. ... if we can restore something to its natural state, why not?" Why not, indeed.

Link: http://www.cbsnews.com/stories/2006/08/07/eveningnews/main1872163.shtml

Cryonics Documentary on Google Video

The Zig Zag cryonics documentary previously mentioned at the Longevity Meme - and recently shown on British TV - is available at Google Video. Get it while you can.

"The first ever footage of a person being cryonically frozen is to be broadcast in a Channel Five documentary that will follow a woman who is terminally ill with cancer before and after her death. ... We're really very proud of what we have achieved with this programme - the human and emotional journey we captured with one contributor in particular, filming prior to her death and the subsequent process of her preservation, in conjunction with the amazing scientific and ethical questions raised by this subject, makes for one of our most challenging and fascinating productions to date." Filming was earlier this year, according the Alcor newsletter; I'm hoping this turns out to have more of a respectful positioning than the Guardian article suggests. Cryonics is an essential insurance policy; the best and only option available to all too many people who will die before the onset of meaningful healthy life extension technologies.

Take a look and make your own mind up on the tone and positioning. I suspect that the cryonics industry and community is in much the same position as the rest of the healthy life extension community: the core proposition is compelling for many people, but still largely unknown or poorly understood. The largest obstacles lie in educating more of the general public, raising funding, expanding advocacy efforts and growing support; there is no such thing as bad publicity under those circumstances.

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Work, Retirement and the Times They Are A-Changing

Our healthy life spans are increasing as a result of general advances across the board in medical science. Now, scientific and activist communities are gearing up for serious efforts to deliberately push back age-related degeneration further and faster than before. Change is coming to aging, healthy longevity and - as a direct consequence - the arrangement of your personal finances in later life. The actuaries know already, and so do the gerontologists, but everyone else seems to be lagging behind a touch in the marketplace of ideas.

What does this all mean? It means a certain persistence of old ways of thinking about age and worth of folk in the employment marketplace, for one - both on the part of employers and employees, and to the detriment of both sides. A recent Globe and Mail article hits many of the right points, but fails make the next essential leaps of logic - thereby reinforcing my point above, I think:

"A fair amount of age discrimination still exists, but it is couched in terms such as a person won't fit in or that they are overqualified or that they may be too expensive," says Barry Witkin, founder of Prime50, an employment service for workers aged 50 and older.

There is no reason that today's older workers cannot remain productive -- "the 50-plus age group is really the new 40-plus, mentally, physically and emotionally," Mr. Witkin says.

Yet, despite widespread predictions of looming labour shortages as baby boomers move into retirement range, employers are not courting those experienced older workers who want to remain in the work force, Mr. Witkin says.

"Employers are still holding on to the myths and false perceptions of the 50-plus worker without recognizing the reality of this age group."

Needless to say, this state of affairs won't be contining for long in those locales where you are actually free to continue working at any age. (Enforced retirement by age is one of the many little monstrosities that come with socialist ideals as practiced in modern "representative" democracies). It's simple economics; more healthy people means a greater demand for services, which means a greater demand for workers, which means higher wages or more expansive hiring criteria. It's happening already, as demonstrated by the very existence of organizations like Prime50.

It is quintessential human nature that raw self-interest is the only thing to reliably overcome outmoded prejudice and preconception - or indeed any of the other worse sides of humanity. The most elementary expression of self-interest is trade; be it eggs, intangibles or time and salary. If that process takes too long, the older healthy folk will simply get out there and start or participate in their own companies. After all, they're at a stage in life where most have the financing saved away to do just that.

In a world in which more and more people are healthy and active at ever older ages, and medical technologies to enhance longevity are advancing at a rapid pace, the culture of retirement will not remain as it is today. There is too much to be done, too many opportunities for the taking.

Retirement in the future will become something quite different from what it is today. I think we will see two forms of retirement in this future without aging. Firstly, there will be the extended vacation. A worker will finish a career with enough money saved to go on vacation for a few decades. That should be more than enough time to decide on a new direction in life.

Secondly, an ambitious worker could save enough wealth to remove the need for income - they could live on capital gains, the return on investments, and all the normal methologies of the well to do in the present day. Given enough time, even the most lowly of jobs could produce this sort of wealth, necessary for a permanent vacation.

Of course, this won't result in a world of perpetually vacationing people. If everyone is resting on their laurels, there would be no one to produce goods and provide services. So a dynamic equilibrium would arise between the vacationers and the working - too few workers and prices rise, so more vacationers return to work (out of necessity, or looking to make a killing in a hot market). If many people are working, prices fall, so more can afford to become long term vacationers.

There is no need for anyone to interfere in this process, as people will adapt and shape to match their new capacities. This is just as it always has been, given the (continuing) increase in life expectancy over the past century.

If you take one thing away from thinking about the future, retirement and work in later life it is this: save now, and wisely invest as much as you can. The freedom to choose your path in decades to come depends entirely on having the wealth of savings, investments and a few decades of compound interest safely behind you. You will have a great deal more choice than your parents - but a poor man has no choice at all, be it 1950 or 2050.

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Funding For Synthetic Biology

As this release shows, the field of synthetic biology has found its feet; the level of recognition, support, collaboration and ongoing work has risen to the level at which centers are being founded. "Funded by a five-year, $16 million dollar grant from the National Science Foundation (NSF), the Synthetic Biology Engineering Research Center, or SynBERC, is gathering pioneers in the field of synthetic biology from around the United States ... Synthetic biology is the design and construction of new biological entities such as enzymes, genetic circuits and cells, or the redesign of existing biological systems. The field builds upon advances in molecular, cell and systems biology and seeks to transform biology in the same way that synthesis transformed chemistry and that integrated circuit design transformed computing." To me, the significance of this field lies in the new capabilities that could be directed to repair age-related cellular damage in our existing biology. Protofection - replacement of age-damaged mitochondria - is an early example of this sort of capability. We'll be seeing much more in the years ahead.

Link: http://www.berkeley.edu/news/media/releases/2006/08/03_SynBerc.shtml

An Introduction to p53, Cancer and Aging

A long article from the Times Online looks one present focus of modern cancer and aging research: "The [p53] gene keeps cancer at bay, and scientists are racing to find a wonder drug to harness its power. If they get it right, we'll live longer, healthier, cancer-free lives. ... [aging and cancer are] two sides of the same coin, sharing a common mechanism in which the scales can be tipped either way. In other words, that wrinkled skin, thinning bones and failing organs may be the price we pay in the long run for holding cancer at bay. ... The clinical implications are clear. People are beginning to ask, 'Can I manipulate the system to get the best of both worlds?' ... Drugs to manipulate the p53 system to protect against cancer and slow down ageing at the same time are even further over the horizon, but scientists working to understand this relationship are making some sensational discoveries."

Link: http://www.timesonline.co.uk/printFriendly/0,,1-531-2290578-531,00.html

Thought For the Day: Let's Get the Job Done Already

I noticed a good thought for the day prompted by an article on healthy life extension and aging science from earlier this year:

As a believer in the ability of human being, using the scientific method, to achieve almost anything I have no doubt whatsoever that we can end aging. If progress can be made with mice it can be made with men. A man is a more impressive creature than a mouse but biologicly they are equally complex.

...

Unnecessary death annoys me. If the survival of the individual is not a "social good" then be damned to whoever holds that notion of society. I think we should start thinking about what to do to ameliorate the inevitable problems but that we should SPEND THAT MONEY.

Spend the money and get out there and fix the problem already - and support those who are already working on it. Life's normal array of problems plus more healthy, vigorous, experienced folk to tackle them has to be better than the age-related suffering and incapacity of hundreds of millions plus the death of one hundred thousand each and every day.

One day - the day you try not to think about - this will all be a very personal, vital issue for you. What sort of future would you rather live in: one with or without advanced medicine capable of repairing age-related cellular damage before it leads to frailty and death? If you choose life and health, it's up to you to make sure that future happens, and happens soon enough to make a difference.

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Longevity, Evolution, Mitochondria

Good basic science in this paper, relating biochemistry, evolution and mechanisms for longevity: "The amino acids sequences of the mitochondrial DNA-coded peptides of placental mammals evolved at different rates in different branches of the mammalian phylogenetic tree. ... Mitochondria generate reactive oxygen species (ROS) that appear to constrain the life span of many species. Therefore, I tested the hypothesis that the evolution of mammalian longevity drives the accelerated evolution of mitochondrial DNA-coded peptides. ... It is suggested that, in mammals, adaptive selection of mutations that decrease the rate of production of reactive oxygen species, [directly or indirectly], increases longevity." Longevity need not be selected for directly. Reliability theory suggests that gains in health and function during youth selected for in this manner will incidentally lead to increased longevity - less oxidative damage leads to a longer life. You can learn more about evolutionary theories of aging and longevity at Fight Aging!

Link: http://dx.doi.org/10.1016/j.mad.2006.06.001

Understanding Embryonic Stem Cells

EurekAlert! reports on an important advance in understanding just what makes an embryonic stem cell an embryonic stem cell: scientists "have found that the DNA of human embryonic stem cells is chemically modified in a characteristic, predictable pattern. This pattern distinguishes human embryonic stem cells from normal adult cells and cell lines, including cancer cells. ... Our results suggest that therapeutic cloning of patient-specific human embryonic stem cells will be an enormous challenge, as nuclei from adult cells will have to be epigenetically reprogrammed to reflect the specific DNA methylation signature of normal human embryonic stem cells. This reinforces the need for basic research directed at understanding the fundamental biology of human embryonic stem cells before therapeutic uses can be considered." Informed commentary on the difficulty of creating embryonic stem cells from adult cells is a big step up from not knowing how to do the job.

Link: http://www.eurekalert.org/pub_releases/2006-08/cshl-hes080106.php

Progress in Cancer Vaccine Research

From EurekAlert!, a long overview of recent advances towards cancer vaccines: "for the first time, the prospect of eradicating a specific cancer through vaccination is possible. ... researchers are working on the next era of vaccines designed to treat cancer that has already developed. These vaccines don't rev up the human immune system to attack an invading microbe, but prime the system to go after a unique biological tag found only on tumor cells. ... Hypothetically, once the immune system has been sufficiently stimulated, it would be able to find and destroy every single tumor cell throughout the body ... It could do this without destroying healthy tissue. That's the goal we strive every day for. ... This is an exciting time in cancer research, given our increased understanding of the molecular nature of cancer and the immune response." The defeat of cancer is a very necessary step on the road to radical life extension.

Link: http://www.eurekalert.org/pub_releases/2006-08/uotm-nhi080406.php

On Zebrafish Regeneration

From PLoS Biology, research into the regenerative capabilities of zebrafish: "Injured mammalian hearts cannot regenerate; instead, they scar. ... By contrast with mammals, newt and zebrafish hearts regenerate after amputation. The molecular mechanisms underlying this phenomenon have not been characterized in newts because of a lack of genetic tools. Recently, we and others showed that zebrafish fully regenerate myocardium after 20% [amputation of the ventricle]. ... zebrafish hearts regenerate by cardiomyocyte proliferation, whereas fin regeneration involves the formation of a blastema, a mass of proliferative, pluripotent progenitor cells ... we hope to elucidate the molecular mechanisms underlying heart regeneration in lower vertebrates. We have identified genes that serve as regulators during heart regeneration ... these genes represent promising candidates for future therapeutic approaches in regenerative medicine."

Link: http://biology.plosjournals.org/perlserv/?request=get-document&doi=10%2E1371%2Fjournal%2Epbio%2E0040260

The Longevity Dividend: A Call for Endorsements

You may recall that S. Jay Olshansky, Daniel Perry, Richard A. Miller, and Robert N. Butler kicked off their Longevity Dividend initiative earlier this year with a cover article in The Scientist. Olshansky et al are moving forward with the next phase of this initiative, as relayed by the Gerontology Research Group list.

Dear Fellow Scientists and Public-Health Advocates:

In March of this year we published an article in The Scientist entitled "In Pursuit of the Longevity Dividend" in which we contend that the time has arrived for governments and national health care organizations to invest in the extension of healthy life by recognizing that one of the most efficient ways to do so would be to aggressively pursue the means to slow aging in humans. We suggest that even a relatively small deceleration in the rate of aging would yield the equivalent of simultaneous major breakthroughs involving every major fatal and non-fatal disease and disorder associated with aging. As a way to follow through with our recommendation, we are planning an event on Capitol Hill on September 12, 2006. At this event there will be U.S. Senators from both sides of the aisle, Nobel Laureates, representatives of national and international health organizations, and scientists - all of whom will be advocating an investment in the pursuit of the Longevity Dividend. We would like the two-page document cited below to represent a summary of our collective enthusiasm and support for this effort - a document we anticipate will be endorsed by a large number of scientists, health advocates, public health experts, and anyone else interested in seeing an increased effort to pursue the extension of healthy life. This document will be handed to representatives of Congress as evidence of our commitment and support. We would like to you consider placing your name on this document. Should you decide you are willing to lend your name to this, please send an E-mail with your name as you would like it to appear, your degree(s), and affiliation to S. Jay Olshansky [sjayo@uic.edu] with Longevity Dividend in the Subject Heading. In most cases a simple reply to this E-mail would suffice. A copy of the final document will be sent to everyone just before the September 12th event. I would encourage you to disseminate these articles far and wide - we see this as an international effort.

With best wishes,

S. Jay Olshansky, Daniel Perry, Richard Miller, and Robert Butler

------------------

"Pursuing the Longevity Dividend: Scientific Goals for an Aging World"

[Endorsers to be listed in alphabetical order]

Aging for both populations and individuals is on the verge of a new era. Humans are approaching old age in unprecedented numbers as a result of large baby boom cohorts born in the middle of the 20th-Century that are approaching traditional retirement ages. Increases in the prevalence of age-related disease, frailty, and disability are visible harbingers of the potential costs and social burdens arising from this historic demographic shift. Advances in the scientific knowledge of aging, however, have now created new opportunities that may allow us and those that follow to live healthier and significantly longer lives than our predecessors. We have reached a historical moment as scientists learn enough about aging to allow us to postpone a wide range of fatal and disabling diseases expressed throughout the lifespan, the result of which would be health and economic benefits for current and all future generations.

Why are we so optimistic now? The primary reason is that science has revealed that aging is not the immutable process it was once thought to be. Interventions at a variety of genetic, cellular, physiological, and behavioral levels not only increase longevity in laboratory organisms, but also dramatically increase the duration of disease-free life. The realization that some humans retain their physical and mental functioning for more than a century suggests that genes associated with the extension of healthy life already exist within the human genome. Biogerontologists have now gone from merely describing cellular aging and cell death to manipulating the mechanisms responsible for these phenomena. Important strides have also been made toward understanding the effects of hormones on cellular pathways that influence the rate of aging. Since these pathways have similar effects in both humans and laboratory organisms, intervention strategies can be evaluated quickly, in short-lived animals, to find the ones most likely to work in humans. In short, we now believe that extending the duration of healthy life in humans by slowing down the processes of aging is a scientifically plausible goal, and adequate funding in this area might well lead to dramatic advances in preventive medicine and public health within the next few decades.

Even a minor deceleration in the rate of human aging could have profound benefits for individuals and societies. Because prolonged, chronic illness is a powerful driver of medical costs, enormous cost savings would be achieved if mortality and morbidity could be compressed within a shorter duration of time at the end of life. At least some of the manipulations that appear to slow aging in animal models do just this, maintaining excellent physical and cognitive function well beyond the usual ages at which illness and disability start to affect most untreated individuals. In fact, aging interventions have the potential to do what no surgical procedure, behavior modification, or cure for any one major fatal disease can do; namely, extend youthful vigor throughout the lifespan. Extending the duration of physical and mental capacity would permit people to remain in the labor force longer, amass more income and savings, and thereby lessen the effect of shifting demographics on age-based entitlement programs, with a net benefit to national economies. The combined social, economic, and health bonuses accruing from a slowing of the rate of aging is what we call the Longevity Dividend - benefits that might begin with those now alive, and then continue for all generations that follow.

We now have good reasons to think that slowing aging in humans is scientifically plausible, and given sufficient research investment might prove to be within our technical grasp in the foreseeable future. There are a number of compelling reasons why this effort should now be aggressively pursued:

(1) the costs, to individuals and to society, of debilitating late life illnesses are already increasing in many countries as the population of elderly people mounts to unprecedented levels, leading to escalating health care costs;

(2) compressing mortality and morbidity into a shorter duration of time at the end of life will pay substantial health and financial dividends for members of the first generation to which they can be applied, dividends that will be compounded as new generations benefit from existing and expanding technological advances; and

(3) a modest deceleration in the rate of biological aging would produce the equivalent of simultaneous major breakthroughs against every single fatal and non-fatal disease and disorder associated with growing older.

The time has arrived for governments and national and international health-care organizations to make research into healthy aging a major research priority, exploiting new discoveries towards the goal of manipulating aging rate to prevent or postpone multiple forms of late life illnesses and disabilities. We look forward to developing a national and international strategy that will lead to the permanent extension of healthy life that would result from a successful effort to slow the rate of aging.

As many of you know, I am equal parts enthused by and critical of the Longevity Dividend. It is a big step forward for the conservative position in gerontology; an admission that the debate over healthy life extension is now "how much and how soon is possible." This is wonderful progress when compared with the state of the field even just five or ten years ago. A rising tide raises all boats: the Longevity Dividend approach makes Strategies for Engineered Senescence (SENS) research and the MPrize for anti-aging research more likely to grow and prosper.

In essence, scientific anti-aging advocacy of the past few years, within and without the research community, is bearing fruit. Scientists who have long supported healthy life extension research in private now feel the environment to be safe enough to speak out in public without risking status and funding. This is a huge step forward, as many in the scientific mainstream strongly support the legitimacy of research aimed directly at extending the healthy human life span. But if no-one stands up to say so, funding and legitimacy cannot be established - which is why it is such a big deal that we are now moving away from healthy life extension research as the instant death third rail of grantsmanship.

At the same time, there is much to be critical of. The scope of the Longevity Dividend is unambitious in comparison to what is possible. It is also primarily geared towards government, public funding and political positioning - not my favorite ways of getting things done. Aubrey de Grey, very much not a libertarian, makes a good utilitarian point when he points to the past:

My colleagues in biogerontology have been trying the political lobbying route for decades, and a few successes have been obtained, such as the founding on the National Institute on Aging 30 years ago, but progress has been virtually imperceptible since then because politicians have no reason to listen.

But you should make your own mind up; Olshansky, Perry, Miller, and Butler are demonstrably influential and talented folk. I predict they will attain a good fraction of their goals, having now set their minds to it.

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How To Improve An Immune System

Research into the nuts and bolts of the human immune system shows that increased understanding of any process can lead to potential improvements: "researchers followed T cells as they spent time in the thymus then moved to the body. ... regulatory T cells learn what to protect while in the thymus and that everything the cells learn may not be good
... The findings mean, essentially from the beginning, some people may have regulatory T cells less skilled at keeping the immune system from attacking their bodies and/or too skilled at protecting invaders. It also means one day physicians might steer early education of regulatory T cells in the thymus as a way to vaccinate children against diseases such as lupus, arthritis and type 1 diabetes. Or, they might add regulatory T cells to improve the mix in people who already have some bad [cells]." Your immune system becomes less effective with age due to a bad mix of T cells - strategies of this nature may work to rejuvenate the aging immune response.

Link: http://www.mcg.edu/news/2006NewsRel/Ignatowicz_Pacholczyk080306.html

To Add Decades to Our Life Spans

As a follow up to the wisdom of actuaries on the near future of healthy life expectancy, Reuters sent a reporter to chat with biomedical gerontologist Aubrey de Grey: "Ultra-long lifespans are so far the stuff of science fiction, [but] it is no longer just a dream that people may live decades longer than they do now, de Grey said. The gerontologist said that while some people are skeptical, or even hostile, to the idea that the average lifespan will lengthen, scientific advances are likely to make this a reality. As a result, lifestyles will change. ... decades-longer lives may change traditional patterns of family life, careers, retirement, education and child-raising and force radical changes to pensions. ... These are things that people with expertise with financial planning need to take on board now." Not to mention the rest of us as well - don't expect other people to look after your future health and financial stability. It's up to you to craft the best possible future for yourself.

Link: http://today.reuters.com/misc/PrinterFriendlyPopup.aspx?storyID=2006-08-03T113136Z_01_L0389686_RTRUKOC_0_US-FINANCIAL-AGEING-PENSION.xml

Timelines for Manipulating and Greatly Enhancing Human Regeneration

The convergence of funding and estimated timelines in science is a fascinating process to watch; as a general rule, timelines only start to appear once funding is assured. In other words, when the research and cultural environment is supportive and the field of science in question is well underway. By all accounts, widely available medical technology in ten to fifteen years time will be a quite different beast from that of today:

We have identified a very large number of genes that are involved in the regenerative process and probably just as important, a large number of genes that are involved in the inhibition of regeneration," says Stocum.

Once they find out what allows salamanders to regenerate and what keeps us from being able to, they hope to create a pill or bandage that would spur regeneration in humans.

"Call me Pollyanna but I think yes it is going to happen," says Stocum.

Dr. Stocum realizes it's a lofty goal and one that is still years away.

"Let's put it on a scale of one to ten. We're probably at a three about this point. It's going to take another 10-15 years to accomplish what we want to accomplish."

On the same timescale (and most certainly with or without the government, whatever its employees might think of their own importance) we'll see a newly mature stem cell medicine and tissue engineering of replacement organs.

Within 20 years regenerative medicine will be the standard of care for replacing all tissue/organ systems in the body in addition to extensive industrial use for pharmaceutical testing. The ultimate goal at the end of 20 years is to have real time mass customization of tissues on demand, in vivo. During those 20 years, as our knowledge of tissues grows, it is reasonable to expect to see treatments discovered along the way, roughly at the 5, 10 and 20 year marks. In 5 years the following milestones are hoped for:

  • Develop multiple applications for skin, cartilage, bone, blood vessel, and some urological products
  • Solve cell sourcing issues, giving researchers access to the materials they need to design new therapies
    ...
  • Establish cost-effective means of production, paving the way for future products
  • Establish specialized cell banks for tissue storage, allowing storage of viable "off the shelf" products

    In 10 years, effective regenerative medicine therapies will be available for patient care and industrial research and development purposes. At this time, the following may be achieved:

  • Further understand stem cell and progenitor cell biology
  • Engineer smart degradable biocompatible scaffolding
  • Develop microfabrication and nanofabrication technologies to produce tissues with their own complete vascular circulation
  • Develop complex organ patches, that could repair damaged pieces of the heart or other organs

    Ultimately, within 20 years the full benefits of regenerative medicine therapies will be reached. Some of the applications of regenerative medicine could be:

  • Harness regenerative medicine materials to produce in situ regeneration of diseased and damaged structures in many areas of the body
  • Regenerate most damaged tissues and organs either in vivo or through implanted regeneration therapies
  • Produce in vitro sophisticated 3-D tissues and organs that cannot be regenerated through in vivo techniques, such as an entire heart or lung
  • The more aggressive and optimistic researchers are aiming for first results in a couple of years, while a decade is the more mainstream estimate. We live in interesting times, to see researchers competing to better repair our aging bodies.

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    Examples of Aging Research in Rats

    Via Ouroboros, an example of the impressive rate at which scientists are producing papers on the biomechanisms of aging in rodent species. "calorie restriction preserves the oxidative capacity, though not the levels of respiratory proteins, in skeletal muscle mitochondria. Dietary restriction was also found to delay the increase of T-kininogen, an immune suppressant previously reported to be a biomarker of aging in the rat, as well as the age-related loss of muscle mass termed sarcopenia ... the protein profile of [sarcopenia is] distinct from that of acute injury-induced muscle atrophy. In other words, in muscle at least, we can begin to distinguish between aging per se and simple 'wear and tear' via a molecular measurement."

    Link: http://ouroboros.wordpress.com/2006/08/02/the-week-of-the-rat/

    The Actuaries Know

    (From the Times Online). Of all the people in the world, actuaries have the greatest immediate financial incentive to truly understand the likely future progression of healthy life extension medicine. Vast sums are at stake, which is why archly conservative actuarial culture is actually not too far behind the leading edge of mainstream science in terms of futurism. "For more than 80 years the Continuous Mortality Investigation (CMI) has supplied mortality tables that showed how lifespans were lengthening and how they might continue to improve. Yesterday, the CMI acknowledged after the release of its latest set of tables that there was so much room for error it was no longer sensible to offer a single set of predictions. It said that projections of future mortality had not been done with the latest tables 'because of the uncertainty surrounding future improvements.'" Recent actuarial conference presentations make for interesting reading.

    Link: http://business.timesonline.co.uk/article/0,,8209-2297057,00.html

    On Those Staunch Opponents of Healthy Life Extension

    One of the recent Gerontology Research Group list conversations drifted to the topic of those religious folk who oppose healthy life extension research. Their influence is a hurdle to be overcome in gaining wider support for funding and direction in real anti-aging science:

    We live in a world where a significant fraction of reality (lifestyles, goals, economics, politics, religion, etc.) is built on a foundation that "death" is inevitable and nothing can (really) be done about it.

    This inevitabilility used to be true, and so all the protective mechanisms put in place to avoid thinking about it once made sense. You become stressed, sick and crazy if continually focus on matters you cannot change - and so evolution has led to humans who are very skilled at avoiding this sort of result. People being people, simple rationales became vast, complex, overwhelming cultural edifices over the generations.

    Now, at the dawn of the biotechnology era, the inevitable is no longer inevitable. The research establishment - if sufficiently funded and motivated - could make meaningful inroads into repairing and preventing the root causes of aging within our lifetime. The leftover cultural and hardwired human habits relating to our decay and mortality now actively hinder progress towards the elimination of age-related degeneration, disease, frailty and death.

    Damien Broderick, author of many a book you should get thee hence and read, offered these words from The Last Mortal Generation:

    It is especially ironic, after all, that the most vehement opponents of scientific research into extended longevity - into "immortality", in the restricted sense we have adopted - should be precisely those who foster belief in some other kind of augmented life, beyond death's door, a mysterious deeper life that allegedly surpasses the fact of physical corruption. What is religion's contribution to the debate, in the end, but a systematic and subtle blend of anguish, terror, bargaining, hope, and capitulation and embrace of the inevitable by denying its reality?

    I am in no position to judge the validity of these claims, nor is any mortal, for none of us has returned from the grave to be probed on television or in the laboratory (although the believers in reincarnation would dispute even this). Still, I do not see in the avowals of believers any fundamental objection to the enhancement of life's prospects in this world. Perhaps it is true that mortal life, the only kind we know, is just a preliminary for fuller life in a more elevated condition (or perhaps for endless torment if our choices during life were evil). Well then, the longer we have to savour the rich joys and tests of earthly life, the more opportunities we gain to mature, love, help, build, to take and share responsibility.

    Today we weep to see some child doomed to piteous early death by leukemia. Adults rush to contribute bone tissues that might reverse the errors in the child's genes. In another century, we will feel no less anguish at the sight of ageing and death in anyone at all. Life is as replete and meaningful as we make it, and if we can share in the glories of the world for a thousand years instead of a mere seventy or eighty, I cannot imagine that a loving deity would resent our tenure here, or punish us for living well and long.

    Professor Arthur E. Imhof, a historian of the Free University of Berlin, has lately reflected on the need for a new Ars bene moriendi, one suitable for a time when already we have effectively doubled the traditional expectation of life. Imhof is by no means a technological prolongevist. If the promise of indefinitely extended life does, alas, prove to elude science, we will be well-advised to embrace his humanist prescription. "Let us transform every one of the years gained into fulfilled ones, taking advantage of our immense technical, economic, and cultural resources, and then let us die a natural death." But if it turns out that we need not die after all, if extended life is gifted us in technical solutions to ageing undreamed of by ancient alchemists and mystics, then Imhof's further advice still seems to me sound and bracing, an Ars vivendi for an all-but-immortal future population.

    "Gained years are not necessarily fulfilled years. We have to fill them with meaning. If people spend their lives interested only in physical activity but not in spiritual cultural matters, they should not be surprised to find themselves confronting a great spiritual emptiness when their physical powers wane in old age and they do not know how to fill the extra days, months, and years. But this need not be so: the situation could be prevented with a lifelong cultivation of spiritual and artistic interests."

    Those interests - obsessions, perhaps, indulged across centuries of freshly garnered information and insight - will include, for many, the topics we have touched on in this book: the nature of mind and consciousness itself, of life natural and artificial, and of cosmos great and small, the quest for intellectual clarity, and perhaps our emerging role as custodians and shapers of the whole future universe. And within that passionate quest for understanding, we will surely also seek to nourish the quiet, serene truths Imhof recommends: arts of living well, and if death is, after all, finally unavoidable, however long postponed, of dying well.

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    Timelines For Regenerative Therapies

    The common wisdom on widespread availability of stem cell based regenerative therapies for age-damage tissue is repeated in this CNN article: "stem cell therapies for degenerative disorders afflicting major organs such as the heart and liver could be available within 10 years. ... What we're going to see is one or two patients being helped in some way and people are going to hail it as the end of Parkinson's and Alzheimer's. But it's going to be a slow process. We hear an awful lot of hype about what stem cells can do but in reality there's still a lot of work to do ... the pace of progress would depend on increasing the number of suitable cells made available to scientists - and warned that a great deal of 'fundamental research' still had to be done before stem cell applications were ready for clinical trial." The first of the first generation autologous and transplant stem cell therapies are moving ahead successfully today, but sophistication, reliability and better economics take time.

    Link: http://edition.cnn.com/2006/TECH/science/08/01/feature.stemcells/

    From Around the Blogosphere

    A list of items and interests I've skipped over in the past week for your entertainment today. We'll kick off with a new addition to my links, Ouroboros, which seems like a promising start:

    In conjunction with exciting news about the use of passive immunization (administration of antibodies, rather than raising them inside the patient by administering an antigen) against amyloid, also announced at the 10th International Conference on Alzheimer's Disease in Madrid, this news indicates that the next decade will see a revolution in the way that Alzheimer's disease is treated clinically. Rather than merely forestalling the symptoms of cognitive decline, the new generation of drugs will attack the root cause of the disease. Furthermore, anti-amyloid therapies have the potential to be used preventively, rather than after symptoms have already manifested.

    I've also been meaning to link to this vision of the future from Kevin Perrott:

    She had to admit, she was very happy with her progress thus far. Looking at some of the others of her age group who had entered the program at the same time, she was an ideal responder. Whether through lucky genetics or perhaps just because her body had not accumulated the same amount of damage as others, she was at least 6 months ahead of the average and would likely continue to progress further than the normal endpoint. Her doctor thought that she might be able to reverse her biological age to perhaps her early 40's or late 30's. She felt very lucky that the reparative therapies were working so well for her.

    ...

    The above is a scenario held in the not too distant future perhaps as few a two or three decades, where new technologies such a stem cell and genetic therapies are able to repair the damage that accumulates with age, restoring function to the body and increasing healthy longevity. Of course there is nothing even remotely resembling the therapies which Alice is taking available today. Diet, exercise and good lifestyle choices are still the gold standard when it comes to living a healthy and long life. Still, these therapies are being developed and it is only a matter of time so it is a very good idea to do what we can now to help increase our chances of being around when they do become available.

    In response to recent mainstream articles on the growth in healthy longevity over the years, the Cato Institute blog authors make a point that should also be knee-jerk reflex for me while writing on these topics.

    The introduction of the institutions of economic freedom in the Netherlands, Great Britain, the United States, and then the rest of the world beginning around 1700 caused what historian Steven Davies calls a "wealth explosion." A great part of the unprecedented wealth creation went into sanitation and more abundant food and later into the research necessary to produce vaccines and antibiotics. Those institutions include secure private property, the rule of law, open markets, and economic freedom generally - or what Adam Smith called "peace, easy taxes, and a tolerable administration of justice."

    Capitalism has made the West rich and thus healthier and longer-lived. It could do the same for Africa, Asia, and the Arab world.

    Randall Parker also commented on longevity, chronic disease and the benefits of modern medicine over at FuturePundit:

    Even if one does not die while infected the infectious diseases take their toll and accelerate aging in a number of ways. First off, the pathogens directly do damage to the body. Second, the immune system's response does damage. In the process of attacking pathogens the immune response causes collateral damage to human tissue. Chemical compounds released by immune cells do damage to our own cells. Third, infection reduces our ability to stay nourished due to decreased appetite, diarrhea, decreased ability to do activities that bring in food, and other mechanisms. Therefore a reduction in infectious disease exposure has reduced the rate at which our bodies accumulate damage.

    Conventional wisdom has it that people live longer today because when they do get sick medical treatments can keep them alive. But Dr. Fogel's study of US Civil War veteran medical records shows that back then people got serious illnesses at much younger ages, decades sooner. They lived with these illnesses for much of their lives.

    I recommend you familiarize yourself with the reliability theory of longevity and aging - it is a simple yet powerful way to frame present day aging research and our understanding of cellular damage, disease, aging, longevity and modern efforts to engineer longer, healthier lives.

    As it so happens, Leonid Gavrilov and Natalia Gavrilova, who applied reliability theory to aging, will be lecturing at the Buck Institute for Age Research this week. You can find links to the powerpoint lecture materials posted to Gavrilov's blog.

    Back to FuturePundit, some thoughts on the recent ampakine research that I also found interesting:

    I am surprised this was so easy to do. Some aspects of brain aging will require gene therapy, cell therapy, and other techniques to reverse. But this study's results strongly suggest that conventional drugs will play an important role in preventing and reversing brain aging.

    ...

    The economic impact of drugs that reduce and reverse brain aging will be huge. People in their 50s, 60s, and 70s will be far more economically productive when brain aging can be reduced and even reversed. The question isn't whether this can be done but when it will be done.

    Finally, Michael Anissimov notes that the Singularity Institute is doing very well for itself. Like the Methuselah Foundation and the Center for Responsible Nanotechnology, the Insitute is a significant result of the energy of the transhumanist movement and culture of the turn of the century. As I've said before, we can learn a great deal from the manner in which the folk at the Singularity Institute have engineered their success of the past year or so. Lots of hard work, but cleverly applied hard work.

    Now we just need a few longevity-focused organizations to achieve that very same level of break-out momentum and level of funding - being a first things first sort of person, I'm rooting for progress in healthy life extension before any other other transhumanist goals. The Methuselah Foundation is well on the way, but the more the merrier.

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    On Inflammation and Disease

    Via Scenta, a popular science piece on the bugbear of chronic inflammation: "When an infection occurs, immune cells flock to the area and secrete large amounts of highly reactive chemicals to combat the invader. But these inflammatory chemicals also attack normal tissue surrounding the infection and damage critical components of cells, including DNA. During chronic inflammation, the damage may lead to mutations or cell death and even to cancer and other diseases. [Researchers] have discovered that the DNA damage produced by one of these inflammatory chemicals, nitrosoperoxycarbonate, occurs at unexpected locations along the DNA helix. The finding counters the prevailing theory about where the DNA damage occurs and may shed light on new ways to diagnose and combat inflammation ... We need to understand the mechanisms of inflammation in order to make new drugs that will break the link between inflammation and disease and to develop predictive biomarkers."

    Link: http://www.scenta.co.uk/scenta/news.cfm?cit_id=997466&FAArea1=widgets.content_view_1