Artificial Skin, Artificial Bone

Work towards artificial organs provides good competition for the young field of tissue engineering - scientists in both fields are moving closer to viable replacement organs; I would expect to see interesting product lines on the medical market from both fields in 2016. I recently noted research into artificial skin at the Longevity Meme, and here is an article to match on developing better materials for artificial bone:

For the past several years, Tomsia and colleagues have worked to fabricate artificial bone that is more bone than artificial, meaning it adapts to changing physiological conditions and meshes with surrounding tissue over time. In contrast, today's artificial joints are made from metal alloys and ceramics that often trigger inflammation and immune responses, or may require corrective surgery after only a few years. The need for better biomaterials is further underscored by the growing demand for artificial joints. More than 150,000 hip replacement and nearly 300,000 knee replacements were performed in 2000, according to the National Center for Health Statistics. These numbers are expected to swell in the future as baby boomers age.

Because of the pressing need for longer-lasting artificial bone, researchers like Tomsia have developed materials that take their cue from nature. In this case, Tomsia and colleagues turned to the ocean. When seawater freezes, crystals of pure ice form layers, while impurities such as salt and microorganisms are expelled from the forming ice and entrapped in channels between the ice crystals. The result is a layered structure that roughly resembles nacre's wafer-like construction.

To me, the near-future area of most interest is the blending of prosthetics and artifical replacements with tissue engineering and stem cell medicine. Scientists are heading towards hybrid technologies that take the best of both worlds - the reliability and range of materials science coupled with biological tools that handle the complexities of growth and structure. From that article on artificial skin:

"This technology is taking us many steps closer to real skin, which is our goal - to make something in the laboratory that is as close as possible to the structure and function of natural skin ... To reach that pinnacle, the skin will need some other, crucial ingredients it doesn't yet contain: pigment cells to restore skin color, and - especially - endothelial cells to form blood vessels that are required to supply the skin with oxygen and vital nutrients. ... Although an ideal artificial skin is still years away, scientists can see real, tangible progress in their efforts to mimic the hugely complex mesh of fibers, sweat glands, hair follicles and blood vessels

Ultimately - within 30 to 40 years, if we keep to to a Kurzweilian timescale - we're going to see the spectrum of artificial replacements far outpace standard issue human biology in terms of cost, performance and reliability. That will certainly be interesting...

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A Strategy for Autoimmune Disease

(Via EurekAlert). Researchers have demonstrated an apparently viable strategy for dealing with autoimmune disease: "The patients' own bone marrow stem cells were harvested from their blood. ... Next, in a process that usually requires a few weeks of hospitalization, patients immune systems were virtually destroyed through high doses of chemotherapy. Then the cleansed stem cells were returned to the bone marrow to repopulate the marrow and body in an effort to regenerate a healthier immune system. ... 50 percent of the 50 patients in the study had disease-free survival at five years with an overall five-year survival rate of 84 percent." Chemotherapy will be replaced with more effective, less unpleasant methodologies in the future, such as nanoscale delivery systems demonstrated by cancer researchers.


A Look at Calorie Restriction

The Post-Gazette is carrying a nice piece on the practice and science of calorie restriction. The author manages to avoid most of the poor characterizations of CR that crop up in the mainstream media: "New research shows that calorie-restriction diets - which cut calories by as much as 40 percent of your normal intake - may help you live a longer life. ... What is so surprising is that people who follow calorie-restriction diets in hopes of living longer are still eating a lot of food. They indulge in huge breakfasts and big dinners, but eat few or no snacks in between. The main difference in their diets compared with most people typically is in the nutritional quality of food they eat -- whole grains, fruits and vegetables and less animal protein and saturated fat. They avoid refined foods, sugary desserts, soft drinks and other sources of 'empty' calories."


On Artificial Skin

The LA Times takes a long look at the state of research into artificial and tissue engineered skin: "This technology is taking us many steps closer to real skin, which is our goal - to make something in the laboratory that is as close as possible to the structure and function of natural skin ... To reach that pinnacle, the skin will need some other, crucial ingredients it doesn't yet contain: pigment cells to restore skin color, and - especially - endothelial cells to form blood vessels that are required to supply the skin with oxygen and vital nutrients. ... Although an ideal artificial skin is still years away, scientists can see real, tangible progress in their efforts to mimic the hugely complex mesh of fibers, sweat glands, hair follicles and blood vessels ... We've learned a lot in the past 10 years. A real critical mass is forming around this technology."


Thailand and Stem Cell Research

Thailand seems to be a welcoming destination for organizations involved in stem cell research and the development and commercialization of first generation regenerative therapies. The Thai government is getting more involved - which will no doubt result in regulation to make the local environment much less attractive. Politicians are nothing if not adept at poisoning the roots of progress:

Thailand will set up a national committee to build the underlying framework for the kingdom's systematic study of factors concerning research and development (R&D) of stem cell applications to prevent exploitation from foreign firms, according to a report by the Thai News Agency (TNA) Thursday.

Public Health Minister Pinij Jarusombat who chaired a meeting on the nature and direction of stem cell study Wednesday, said that stem cell research gives hope for cures for some, otherwise, incurable diseases.

According to Pinij, participants agreed to the setting up a special committee to support the development of stem cell research to achieve the utmost benefit for Thailand and to reduce duplication of overlapping of activities.


Department of Medical Sciences Director-General Dr Paichit Warachit said that there are several organisations in Thailand which have conducted research on stem cells, including the National Blood Centre and medical schools.

Medical Council of Thailand president Prof Somsak Lolekha said that the US has yet to allow stem cell treatment in patients with coronary heart disease because there are no existing laws controlling safety procedures in stem cell treatment -- or a unifying standard.

The most interesting tidbit comes at the end of the article, noting that "several overseas companies want to set up laboratories for such activities in Thailand." It's clear that TheraVitae's high profile success in Thailand with the VesCell technology is steering further investment into similar business models. As one of the few things likely to relax the stranglehold of Western politicians and regulators on research and development, more medical tourism and overseas development is a good sign.

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The Public Face of A4M

It's interesting to see where the American Academy for Anti-Aging Medicine (A4M) is going with their messaging these days: "By Klatz's definition, anti-aging is any intervention that has to do with early detection, prevention or reversal of age-related conditions and diseases. ... Klatz envisions an era of technologies that will slow or even reverse the 'dysfunction' he calls aging - or what everyone else simply calls the process of life." This Digital Journal article is an interesting mix of right on the money and a conflation or papering over of the old, bad "anti-aging" marketplace - a staple of the A4M conferences - with the meaningful science of the future. Some mix of rebranding and repurposing at work, in other words; A4M has always been an organization with the potential to do far more good for the future of real anti-aging medicine than they are in fact doing.


Mitochondrial Transfer as Healing?

A most interesting New Scientist article looks at hints of an existing mechanism by which age-damaged mitochondria could be repaired. Given the central role played by mitochondrial degeneration in aging, this would be a very big deal if it could be exploited: "Healthy cells seem to have shown an amazing ability to breathe new life into damaged ones by rejuvenating their defunct mitochondria. It is an extraordinary and controversial claim. But if confirmed it could offer a way to prevent a range of harrowing metabolic diseases that affect millions of people. Experts in mitochondrial research have yet to be convinced. They say the work purporting to show the effect has yet to be comprehensively peer-reviewed, and is so potentially ground-breaking that more evidence is needed."


4th Annual Calorie Restriction Society Conference, April 6-9 in Tucson, Arizona

The early registration deadline has slipped past for the 2006 Calorie Restriction Society Conference, to be held near Biosphere 2 in Tuscon, Arizona this coming April. There's still plenty of time to register and sort out other necessary details, however.

As more funding comes into calorie restriction research - and related investigations into the intersection of metabolic biochemistry, genetics and longevity - the CR Society conferences have attracted more scientists alongside practitioners and advocates of a calorie restriction lifestyle. This is a very good thing in my eyes; building bridges on common ground between the scientific community and pro-longevity research interest groups is a proven way to make progress. You may recognize some of these guests and speakers from news and events of the past few years:

Steven Austad, Caleb Finch, Luigi Fontana, Aubrey de Grey, John O. Holloszy, Edward Masoro, Michael Rose

The 2005 conference was a promising success, and the upcoming April gathering should benefit from additional media attention and interesting new science from the past year.

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Exploring Life Extension

The Immortality Institute film Exploring Life Extension can now be found at Google Video thanks to Institute volunteers. You can also order a free DVD beta cut, or search for one of the several bittorrents. The film is a much condensed summary taken from hundreds of hours of interviews with members of the healthy life extension community, and a good first effort from the film crew. There's much more to be mined in the source material, however. A version two, with the benefit of greater editing experience and some fresh eyes on the interviews would be a worthy project. There's a lot to be said for this sort of community anthropology as a way of effectively delivering a message to a wider audience: radical life extension is a noble, plausible, possible goal.


You Can't Take It With You

The latest round of publicity for cryonics was kicked off by thoughts on the age-old question of how to take your wealth with you - or at least keep it intact for later. This age-old question becomes somewhat more practical to consider when there is a non-zero, albeit unknown, chance of returning to society at some later date. A discussion is ongoing in the Extropy-Chat list (threads here, here and here) on this and related matters of how best to ensure your decisions are respected when you are no longer available to exert your own force of will.

When thinking about these matters, it's best to look at the incentives rather than the details. The trouble with property left undefended, as the ancient Egyptians and every other culture that buried wealth with the dead has handily demonstrated, is that no-one else's interests are aligned with yours. You'd like your wealth - in whatever form it happens to be in - to be your property once more when you are revived from cryonic suspension. Every other person in the world will benefit from taking these resources for themselves while you are out of the picture.

Options would seem to fall into the following categories:

  • Give the resources to some group you have charged to maintain them: perpetual trusts, complex legal manipulations, or simple trust absent the structures of law.

  • Convert the resources to something easily hidden and likely to retain some value due to scarcity - such as gold, or better, a cache of historical data - and hide it well.

  • Disburse all of your resources as you see fit and go into suspension with nothing to your name.

The inherent conflicts of interest mean that resources given over in trust are going to be raided or taken from you sooner or later - the only questions lie in the details of that theft.

Hidden wealth might seem to be a more attractive option - removing the human element insofar as that is possible - but any choice may turn out to be worth less than the dirt piled atop it. Hiding wealth as gems might have looked smart half a century ago, but gems will be be a mass-produced item within a decade. With advanced enough technology even rare elements are a mass-produced item. This is not even to consider that the society advanced enough to return you from cryonic suspension may just be advanced enough to scan your vitrified brain and read your memories of hidden caches from its fine structure.

Putting your body and brain into cryonic suspension is an educated gamble, we must recognize that much. I think it's a good gamble, since technology is advancing rapidly and comparatively few interests are aligned against you in the matter of revival and returning to a place in society. Trying to put your resources, your wealth, on ice strikes me as a much more risky endeavor - the long history of human attempts to take action or enforce a decision after death should amply demonstrate the futility of attempting to preserve post-mortem vision and wealth from the predations and honest choices of your fellow human beings.

But so what? If the future deals you a bad hand prior to the arrival of working anti-aging medicine, and cryonic suspension is the only alternative to the grave, then direct your wealth to those organizations that are working to produce the sort of world that will revive you and that you'd like to live in. I don't see that you can do better than that. If you should happen to be revived with nothing but a brain, body and debt in the future, then what of it? We've all conquered that situation at least once already; alive and challenged to win once more is a good deal better than the alternative.

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More Klotho Research

Kevin Perrott notes new research on the Klotho gene: "Released just yesterday are two papers which describe more detail of the story behind Klotho, unravelling some nuances which in days gone by would have taken further years or even decades to uncover. The first paper describes how Klotho exerts its anti-aging effects by binding to and increasing the influence of a factor on cell growth while the second paper shows Vitamin D to play a direct role in this factors activity, showing a potential link between Klotho and Vitamin D." I'm still skeptical of the earlier Klotho experiments, but it seems there's something of interest in the biochemistry. Still, all this metabolic tinkering is no path towards radical life extension - that will require more ambitious, directed strategies.


Another Alzheimer's Mechanism

The biochemistry of Alzheimer's is complex indeed, as illustrated by the fact that after 10 years of massive funding, researchers are still uncovering and debating the significance of possible mechanisms and causes. "The emerging lesson is that cognitive problems in [Alzheimer's] are related to defects in the machinery controlling neuronal connections, not the lesions observed by pathologists ... This new study implicates the PAK enzyme-signaling pathway, which is known to play a role in synapse formation and developmental cognitive deficits, or mental retardation. The PAK enzymes form a family that includes two members known to localize to synapses (PAK1 and PAK3). Both are known to play critical roles in learning and memory. Humans with genetic loss of PAK3 have severe mental retardation. Both PAK1 and PAK3 are abnormally distributed and reduced in Alzheimer patients to an extent sufficient to contribute to cognitive decline."


X Prize Foundation Diversifies Into Biotech

The X Prize Foundation has been reorganizing since its initial success to carry its cachet and methology into other areas of human progress:

We are now evolving the X PRIZE Foundation into a world-class prize institute to create additional radical breakthroughs for the benefit of humanity. We are actively researching the feasibility of new prizes in space, energy, genomics, education, nanotechnology, and prizes in the social arena.

Research prizes work - and have been demonstrated to work very well, time and again. This is why I, the X Prize Foundation, and a great many other people support the MPrize for anti-aging research; if you want to get something done in a moribund and logjammed field of science - such as goal-oriented, plausible healthy life extension research - then you should start offering research prizes. Given that, it's interesting to hear that the next X Prize Foundation is to be in a core area of bioinformatics:

The X Prize Foundation, the group behind the $10 million prize for human space flight, 'plans to offer a $5 million to $20 million prize to the first team that completely decodes the DNA of 100 or more people in a matter of weeks, according to foundation officials and others involved,' the Wall Street Journal reports.

The obvious goal here is to kick-start the era of personalized medicine by accelerating existing trends in falling costs and increasing reliability of sequencing technologies. Given the present state of the art, however, this one might get awarded considerably sooner than expected. I suspect there is a more subtle agenda at work; a great deal of technology supports and surrounds the work of sequencing. It's a lynchpin at the heart of biotechnology. Faster, cheaper DNA sequencing will have similar broad enabling effects to the advent of faster, cheaper computers - all sorts of world-changing applications and business plans come out of the woodwork when the cost falls. The world is chock full of ideas waiting to happen just as soon as the startup cost is low enough.

The golden future of biotechnology - and by extension, longevity medicine - rests on making all the enabling technologies, the basic infrastructure, as cheap, widespread and reliable as possible. Onwards to a future of garage biotechnology and open source medical research!

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SIRT6 and Accelerated Aging

Scientists are discovering all sorts of interesting things now that mainstream calorie restriction research is focused on sirtuins: "The research on SIRT6 is part of a broad effort in the Alt laboratory to study the role of a family of seven known mammalian sirtuin genes. These studies were prompted by findings some two decades ago that a yeast counterpart called Sir2 maintains genomic stability and regulates aging in yeast cells. Researchers had also found that enhancing the activity of Sir2's counterparts in the roundworm and fruit fly extended their life span. ... we've found that the SIRT6 knockout produces the most dramatic effects ... The researchers do not know whether the accelerated aging-like effects of losing [SIRT6] relate to its role in DNA repair. Nor do they know whether the degenerative effects are relevant to the natural aging process. However, they said, the discovery offers an intriguing new model for studying DNA repair, as well as its possible role in aging-related degeneration."


Designing Advanced Nanomedicine

As an estimate, scientists are probably 10 years from building proof of concept nanomachines of the sort proposed by Robert Freitas, or shown in this Nanotechnology News Network article. It'll be at least another decade after that to proceed to mass production - but the benefits will be astounding. (Poorly) translated from the Russian: "How we can see, proposed worm design can collect and digest more microorganisms than microbivore. It can move in blood, so it will multiply number of collected bacteria. Nanorobot in bloodstream can collect bacteria and fungus. Worm can also crawl on the tissue surface, so I can imagine worms, crawling on vein's surface to clean out atherosclerosis conglomeration. Worm will be constructed from diamondoid with high precision molecular assembling technology. Worm tracks technology allows fully reprogrammable binding sites, which can make Worm multipurpose device - it can collect not only bacteria or viruses, but toxic enzyme too."


What Will Be the Main Causes of Age-related Death in 2036?

If you're presently younger than early middle age, and not headed into a life of abject poverty, I'd say it's a fairly safe bet that you won't die from Alzheimer's or Parkinson's. Cancer ("malignant neoplasms" to the actuaries) will likely be a chronic annoyance to your health and bank balance - but not fatal. Heart disease and diabetes will be eyed much as tuberculosis is today; killers of the past, now tamed. In short, the causes of the larger numbers in mortality tables will fall to the advance of medicine; some within a decade, others lingering longer, but there seems little doubt that scientists will nail them all within a generation of breakneck research in medicine and biotechnology.

What, then, will be the causes of age-related death 30 years from now? The body is an exceedingly complex machine; blocking off one failure mode, or preventing a single mode of death that results from a class of accumulated damage will leave many other possibilities. Behind the neurodegenerative diseases we know lie a hundred, a thousand ever more subtle and devilish ways in which age-related cellular damage can kill us. You can plug as many holes as you like, but eventually you're going to run out of fingers.

We can plausibly look forward to sidestepping this problem of ongoing damage by replacing an old heart with a young, tissue engineered heart lacking age-related damage. We are within a decade or two of being able to do the same for any other organ or system within the body ... but not the brain.

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

This seems to me to be a far better path forward, that the present dominant paradigm of medical research, and is why I strongly support greater funding for research programs and proposals that take this approach.

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Bona Fide Dopamine Neurons

Via EurekAlert news of a good step forward for the future of regenerative medicine: researchers have "discovered a 'master determinant' that turns embryonic stem cells into bona fide dopamine neurons, brain cells that degenerate in those with Parkinson's disease. The findings hold promise for the future of cell replacement therapy for the debilitating and incurable disease ... The results also underscore the general importance of a thorough understanding of development for producing authentic cells of a desired type from stem cells. ... We spent a lot of effort and are now confident that these are authentic dopamine neurons. If we want to treat Parkinson's patients with stem cells, it will only work if we are able to generate authentic dopamine cells. In the use of stem cells for therapy, it is of utmost importance to make the correct cell type. In the brain, there are at least 1000 different types of neurons, only one of which is clinically relevant to Parkinson's disease."


Other Regenerative Strategies

Wired takes a brief look at regenerative methodologies outside the mainstream of stem cell based therapies: "Hydra Biosciences is working a regeneration drug that stimulates heart muscle-cell regrowth, and could lead to better recoveries for heart attack sufferers. The protein-based drug induces mature cells to become a little bit like stem cells. It causes heart cells to 'dedifferentiate' partially, reverting them to an earlier stage of development and activating their ability to generate more muscle cells. ... The dogma has always been that heart muscle cannot regenerate. But it's possible in animals, and now we have drug candidates that may do the same thing in humans. ... He estimates human trials of the protein compounds will begin within the next few years."


More Use It Or Lose It For the Brain

More studies linking metal exercise with improved resistance to degeneration are rolling in: "complex mental activity across people's lives significantly reduces the risk of dementia. The researchers found that such activity almost halves the incidence of dementia. ... It is a case of 'use it or lose it'. If you increase your brain reserve over your lifetime, you seem to lessen the risk of Alzheimer's and other neurodegenerative diseases. ... individuals with high brain reserve have a 46 percent decreased risk of dementia, compared to those with low brain reserve. All the studies assessed agreed that mentally stimulating leisure activities, even in late life, are associated with a protective effect. ... brain reserve is not a static property, nor that it is determined by early life experiences such as level of education, socio-economic deprivation or poor nutrition. It is never too late to build brain reserve."


Cryonics: Very Much NOT Just For the Rich

Recent mainstream media coverage of cryonics - low-temperature storage of the body and brain after death, awaiting technology advanced enough for resuscitation - has included ABC News coverage that leaves the reader with the impression that cryonics is only for the wealthy:

Being frozen and stored at Alcor isn't cheap.

"Some people just have their heads frozen, believing that in the future they'll be able to use another body," said Tanya Jones, Alcor's chief operating officer. "If you're having your head frozen, it will cost $80,000. The whole body is $150,000."

This omits any discussion of the method most folks - of very modest means - use to fund their suspension: life insurance.

At the time of writing, a 30-year-old can get a 20 year term policy with a face value of $120,000 for as little as $180 per year if she is a non-smoker and in good health.

Starving students can fund it - so you certainly can. You should look on a cryonic suspension agreement as a form of life insurance of its own; it's the best presently available option that gives some chance of avoiding irreversible death if it comes to that. Statistics and common sense tells us that we aren't all going to make it into the era of radical life extension. No-one likes to think about these things, but the consequences of failing to be responsible in any matters of insurance can be dire indeed.

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Regenerating Stroke Damage

ScienCentral reports on a potential method of regenerating damage caused by a stroke: "In the developing systems of young people and other animals, the central nervous system (CNS), which consists of around ten billion nerve cells, have the ability to spontaneously grow new nerve cell connections. ... We know that adults have the same capacity to re-grow, it's just that they're being stopped from re-growing ... Nogo-A is one of the major inhibitors to new growth, there are others but, Nogo appears to be one of the major ones ... In tests on stroke-damaged rats Kartje and her research team used a very specific antibody, an immune-system protein, to stop Nogo-A from binding to receptors on nerve cells. Without the inhibitory affect of Nogo-A, the injured nerve cells were able to re-grow, restoring lost movement to the front paws of the rats."


Nitric Oxide and Stem Cells

Nitric oxide seems to be showing up a fair bit of late in investigations of the biochemistry of stem cells and healing. Digging into the fundament is important - knowing the biochemistry of stem cells means knowing how to control stem cells, and that's the first step on a number of very useful roads. We have this from last month:

... a typical course of hyperbaric oxygen treatments increases by eight-fold the number of stem cells circulating in a patient's body. ... We reproduced the observations from humans in animals in order to identify the mechanism for the hyperbaric oxygen effect. We found that hyperbaric oxygen mobilizes stem/progenitor cells because it increases synthesis of a molecule called nitric oxide in the bone marrow. This synthesis is thought to trigger enzymes that mediate stem/progenitor cell release.

Following that, more interesting research in the past few days:

The problem is rooted in the body's response to vascular injury. The bone marrow churns out cells crucial to repairing the damaged lining of blood vessels. But sometimes they fail to report for duty.

"Part of the defect we think is occurring in diabetic patients is these cells do not carry out appropriate repair, and therefore these patients are at higher risk for cardiovascular disease and other complications," Segal said.


UF researchers isolated these repair cells from blood samples drawn from patients with diabetes and chronic kidney disease and studied them in the laboratory. The cells were unable to move about normally. But when nitric oxide gas was added, Segal said, the cells lost their rigidity, becoming suppler, and their ability to move dramatically improved.

In the body, nitric oxide occurs naturally. It helps the repair cells move out of the bone marrow where they are made, and it opens blood vessels and improves the uptake of oxygen. Patients with diabetes, however, commonly have low levels of nitric oxide.

"We went on to show that actually what's happening is nitric oxide is affecting the skeleton, or scaffold of the cell, and by adding nitric oxide we're able to rearrange the scaffold," Segal said. "When we rearrange the scaffold, the cells are able to migrate. The benefit of this is that when cells have improved movement they are able to repair the endothelium (the lining of the blood vessels) better and perhaps prevent atherosclerosis."

Diabetes acts somewhat like accelerated aging in a number of ways, and has been used as a proxy for aging research in the past. Methodologies that offer the possibility of restoring failing stem cells to duty, or enhancing the capabilities of stem cells in the healthy, are intriguing, to say the least.

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East Bay Calorie Restriction

A feature article in the East Bay Express takes a look at calorie restriction: "Years of studies have shown that severe dietary restriction indeed prolongs life, in lab creatures at least. Yeast on a [calorie restricted, optimal nutrition] diet can live up to three times longer than normal, fruit flies double their average lifespan, and mice that normally live two years can live three or more. Studies on monkeys are ongoing, since primates are naturally long-lived, but so far the calorie-restricted monkeys appear to get fewer lethal chronic diseases and may indeed outlive their well-fed peers. These animals not only live longer, but seem to retain their youthfulness. They are smaller than their counterparts, but more active. They look younger and healthier, are mentally more agile, and have bolstered immune-system activity. The results suggest that eating far less might prevent or slow the onset of a host of human age-related conditions ... The observed changes occur quickly and bring longevity benefits at any age."


It's All in the Delivery Method

The art of destroying bad cells could halt today, and we'd still have very impressive medicine ten years from now due to dramatic improvements in selective delivery technologies. Destroying cells is easy - destroying just the right cells is very hard. Via Newswise: "The disease-finding capability of these scaffolds is due to the specially engineered virus that displays a peptide that matches a protein receptor "zip code" on the tissue of interest. ... previous work revealed that the human vascular system contains unique molecular addresses, depending on the site of an organ or tissue, and that blood vessels also acquire abnormal signatures on diseased organs. ... these nanoplatforms could potentially locate damaged areas on arteries that have been caused by heart disease, and then deliver stem cells to the site."


A View of Proposition 71

Via the Scripps Howard News Service, a look at the state of Proposition 71 and the California Institute for Regenerative Medicine. The opposition of those determined to prevent the development of embryonic stem cell science and resulting cures for age-related disease has put a strong brake on progress - resources poured into battling for control rather than into advancing beneficial medical research. "Instead of financing an accelerating research agenda this year, officials are reduced to begging for handouts to avert closing down by June, when existing funds run out. They also implemented a freeze on most staff hiring. ... It will take about $2.5 million in additional donations, Hall said, for the institute to 'remain active, remain visible and build the infrastructure on which we will launch this big program in the spring of '07.'"


Reminder: Sign Up For the Longevity Meme Newsletter

Now that we're off into year four of the Longevity Meme weekly email newsletter, I think it's time for another of my very infrequent reminders to take the plunge and sign up. There's even an RSS feed for those of you who have progressed beyond email, and you can take a look back at the archive of past newsletters to see if you like what you see before diving in.

Here's a thought for the day from the January 16th newsletter:

If you're healthy, young, and manage to avoid appalling bad luck in the genetic sweepstakes, the future of your longevity and health over the next few decades is all up to you. The advance of medical science makes little difference one way or another - whether you wind up a wreck or not is a function of how you make use of the best strategies for healthy life extension available today - calorie restriction, supplementation, exercise, general good health practices ... the things that aren't rocket science.

As time progresses, however, your remaining healthy life span will be determined ever more by the past rate of progress in longevity research - in other words, how effective the best affordable healthy life extension technologies have become. You have a chance today to make a difference in that rate of progress, to make the future of healthy life extension medicine arrive that much faster; wouldn't it be a good idea to take that chance?

You should certainly do the best you can with the health tools, techniques and technologies of today, but also take time to consider the long-term view. Supporting medical research into extending healthy longevity is important - and it will become ever more important as time goes on that you made the effort to help the development of better longevity medicine.

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Yet Another Heart Stem Cell Trial

A great deal of work is presently taking place on first generation regenerative therapies for heart damage. Here is another example: "The first-of-its-kind study in heart attack patients will seek to demonstrate the safety, and roughly measure efficacy, of three intravenous doses of adult human stem cells versus placebo in lessening damage to heart muscle within ten days of first heart attack. The treatment recently passed an early safety test and has been approved for study in more patients at higher doses. That process will get underway shortly ... The potential to re-build damaged heart muscle by implanting stem cells that then become new muscle cells is one of the most exciting in cardiology."


On Multiplying Stem Cells

For all that the goals and future of stem cell based regenerative medicine are fairly clear, scientists are presently spending more time on the development of necessary infrastructural technologies than on first generation therapies - and quite rightly so. One problem with adult stem cells is "the doggedness with which [cells] differentiate into mature tissue the moment they're isolated from the body. This makes it nearly impossible for researchers to multiply them in the laboratory. And because adult stem cells are so rare, that makes it difficult to use them for treating disease. Now, [researchers] have discovered a way to multiply an adult stem cell 30-fold, an expansion that offers tremendous promise for treatments such as bone marrow transplants and perhaps even gene therapy."


Complexities of Age-Related Blindness

Via Medical News Today, a look at the tough road facing researchers as they work towards prevention and repair for age-related macular degeneration (AMD) and retinitis pigmentosa (RP): "It has been a painstaking scientific journey as AMD and RP each belong to a complex family of disorders, in which every disorder has many forms and each form is encoded with a distinct genetic recipe. Even AMD, a major cause of vision loss in people over 60, is actually a collection of more than 50 diseases. ... Working with fruit flies, the scientists have discovered that a mutation in a common gene called calnexin can derail the light-processing activity of cells and set in motion the gradual breakdown of vision. ... Understanding the basic mechanisms of how proteins are folded holds the key to finding treatments for not only retinal degenerative diseases but also other neurodegenerative diseases such as Alzheimer's, Huntington's and Parkinson's."


A Little Economics and Healthy Life Extension

Following up on a recent call for an economic analysis of staged radical life extension - progression through ever-better medical technologies and ever-greater extensions of healthy life span to reach a form of actuarial escape velocity, always a step ahead of age-related degeneration - Michael Rae has unearthed a 1979 Laurence J. Kotlikoff paper entitled "Some Economic Implications of Life Span Extension" that I think you'll find interesting. The full PDF version is online, a graphic reminder of a time in which typewriters ruled the earth:

This paper is concerned with the following question: what would the economy look like if we suddenly discovered the fountain of youth? While this question may seem fanciful, a growing number of contemporary Ponce de Leons with impressive scientific credentials argue that there is a significant chance of unraveling the mystery of aging in the near future.


In this paper I concentrate on the implications of life span extension for aggregate factor supply and economic welfare. While this the major focus of the paper, I also devote some space to consideration of life span extension's impact on the economy's skill composition and on existing economic institutions, including the social security system.

The major conclusion I draw from my work is that the expansion of working and total life spans should significantly increase economic welfare.


Throughout the paper, "life span extension" is taken to mean keeping people young for longer periods of time. This is quite different from what one conventionally means by life span extension, namely, keeping old people alive for longer periods.

Ah, how we still struggle with this young (healthy) life extension versus old life extension perception today! We call it the Tithonus Error. As we all know, the past generation of advocates failed to establish a research program to match that devoted to cancer or even AIDS, and the widespread public support and understanding such a program requires. The science turned out, as it always does, to be far more complex than anticipated. Hence today we can read a paper set down in 1979 with few signs of its date beyond the typefont. We must do far better now and over the next 25 years - hundreds of millions of lives will be lost if we fail again.

On a slightly related topic, the Wall Street Journal ran a prominent article on the legal methodologies of keeping your finances frozen and yours while in cryonic suspension and thus legally dead. The full text is posted at transhumantech as is usual for this sort of thing:

At least a dozen wealthy businessmen who plan to be frozen after death are testing unfamiliar legal territory by creating so-called personal revival trusts designed to allow them to reclaim their riches years into the future.

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Articles, Articles

A couple of articles of interest to supporters of healthy life extension are available or forthcoming in print (and hopefully online shortly thereafter). Max More notes:

In case anyone is looking for an excuse to pick up a copy of Larry Flynt's Hustler magazine, note that the March 2006 issue (now available) features my cover article, "How to Live Forever." Flip past the lovely Victoria to p.43 and you'll find it.

Have fun.

In addition, the February issue of Life Extension Magazine will feature a Ben Best interview with Aubrey de Grey, covering a range of topics of interest: the Strategies for Engineered Negligible Senescence (SENS), the MPrize, fundraising and advocacy for healthy life extension science, cryonics and the state of scientific anti-aging research today. Keep an eye out for it.

Lastly, the full text of the New Scientist article on aging and mitochondrial science - the piece that prompted a clarifying response from researcher Rafal Smigrodzki - has found its way to the transhumantech list. Take a look and see what you think - overenthusiasm on the part of the author or not? For more information on the work Smigrodzki is a part of - and its relevance to repairing age-related cellular damage - you might want to look back at the Fight Aging! archives. To my mind this research group certainly deserves the attention they are receiving.

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More On Heart Tissue Engineering

Forbes looks at one strand of tissue engineering research and regenerative medicine for the heart: "Merging artificially engineered products with a patient's own heart to stop or reverse cardiac damage could be the wave of the future, researchers say. One such innovation, the 'cardiac patch,' is just that: A piece of living, beating cardiac tissue, grown in the lab in just a few days and applied to hearts wounded by prior heart attack or chronic disease. ... The real challenge is that you have to place the patch upon the heart in a way that it integrates into the heart. You don't want it to just sit there as a separate entity. It needs to connect electrically so that it syncs up with signals coming from the cells, so everything works together. ... animal trials tackling those issues are already under way ... perhaps a decade from now, human trials might begin."


Insulin, Fat, Aging, Calorie Restriction

(Via the LEF News). Synthesis of threads of research into an understanding of a complex system is very rewarding; progress is being made towards this goal for metabolism and longevity: "Caloric restriction and leanness have been shown to increase longevity in organisms ranging from yeast to mammals. Adipose tissue seems to be a pivotal organ in the aging process and in determination of lifespan ... fat-specific disruption of the insulin receptor gene is sufficient to increase lifespan in [mice], suggesting that reduced adiposity, even in the presence of normal or increased food intake, can extend lifespan. The model also suggests a special role for the insulin-signaling pathway in adipose tissue in the longevity process. ... In the control of human aging and longevity, one of the striking physiological characteristics identified in centenarians is their greatly increased insulin sensitivity even compared with younger individuals."


Effects of Healthy Life Extension on Social Security - Volunteers Wanted

Biomedical gerontologist Aubrey de Grey, chairman of the Methuselah Foundation and someone you may recognise from his recent appearance on 60 Minutes, has suggested a volunteer project suitable for economists and statisticians interested in generating greater support and funding for healthy life extension:

A discussion within the Methuselah Foundation has resulted in the idea that it would be good to determine how effective SENS (or equivalently powerful interventions) would be economically: that is, how much they would need to cost before the cost outweighs the economic benefits of keeping someone healthy. Here we are mainly interested in the macroeconomic question, i.e. "cost" is to be understood as how much it costs to administer the therapies (and possibly also to develop them in the first place) rather than how much they might be sold for. Plenty of work has of course been done on this in respect of much more modest [life extension], but no one has quite had the nerve to do it for therapies that conferred escape velocity. I am in touch with people with the necessary enabling technology (datasets, software) to develop such forecasts, but it would probably still be a substantial project. If there are any volunteers who feel they have the right sort of expertise (which means pretty good maths, not just computing) and also a chunk of time to dedicate, please speak up. No guarantees that we can make such a project happen, but we'd like to try.

A discussion is ongoing at the Immortality Institute forums; if this catches your interest, you should certainly drop by and speak up. You might also want to look back in the Fight Aging! archives at a view of the future of retirement (or absence of same), some thoughts on social security and age-related frailty, and commentary on the utter mess that is modern Western-style "social security".

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Interesting Alzheimer's Research

EurekAlert reports on new Alzheimer's research: "Decline of cognitive functions linked to the part of the brain called the hippocampus is a clinical hallmark of Alzheimer's disease. The report demonstrates that targeting excessive glial activation can suppress brain inflammation and neuron dysfunction in the hippocampus and protect against cognitive decline in an animal model. Neuron dysfunction can lead to further glia activation and contribute to further exacerbation of the disease process. ... 188WH and related compounds slowed or reversed the progression of the neuroinflammatory cascade and reduced human amyloid beta-induced glia activation in a mouse specially designed to develop many of the signs of Alzheimer's disease."


TOR Signaling and Calorie Restriction

The researchers working on thousands of strains of gene-engineered yeast in order to understand metabolism and longevity are turning up some interesting science: "We developed a high-throughput assay to determine [life span] for approximately 4800 single-gene deletion strains of yeast, and identified long-lived strains carrying mutations in the conserved TOR pathway. TOR signaling regulates multiple cellular processes in response to nutrients, especially amino acids, raising the possibility that decreased TOR signaling mediates life span extension by calorie restriction." Scientists are turning up all sorts of places to be looking for the biochemical mechanisms of longevity through calorie restriction.


SAGE Crossroads Trading Cards Again - Purchasable This Time

I found the SAGE Crossroads trading cards - each of a noteworthy figure in gerontology, aging and longevity research - to be, after I overcame the knee-jerk Grinch response, an interesting and novel idea. These cards are a helpful educational tool for certain demographics, so it seems worth noting that you can now buy hardcopy decks of the cards at the SAGE Crossroads website. I can think of at least a few folks amongst the regular readers who will appreciate that.

Get your very own collection of SAGECrossroads Trading Cards! This first edition pack includes 50 cards featuring leading researchers working to unlock the mysteries of aging. Each card includes a photograph, quick summary of the researcher's work, and essential information such as specialty and favorite gene.

While I'm on the subject, I'll say that I think it's a shame SAGE Crossroads has fallen off the publishing wagon of late. I suppose the powers that be have more or less curtailed the experiment; as I understand it, the website never achieved the level of popularity that would make it a good investment at the price. Less politics and more science would have garnered more inbound links from my side of the camp, but - judging by the distressing popularity of all things politics these days - that may be poor advice for any listening webmaster-to-be.

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More Gene Therapy For Parkinson's

Via EurekAlert, more good news of progress in the gene therapy field: "Research has shown that mutant forms of the alpha-synuclein gene, as well as too much alpha-synuclein protein, are involved in the development [of] Parkinson's disease in some families. For this research, the Bohn lab combined a recently developed technology called 'RNA interference' with gene therapy to turn off alpha-synuclein in dopamine neurons. RNA interference is a sophisticated method to selectively turn off one gene in a cell, leaving others unaffected. By placing the RNA interference into a crippled, non-disease-causing virus, scientists in the Bohn lab have been able to deliver the RNA interference tool to the brain of rats and turn off the alpha-synuclein protein in neurons. ... This is the first step in developing a new therapy for Parkinson's disease based on molecular knowledge of the disease."


Stem Cell Politics Around the US

The Capitol Weekly takes a high-level look at stem cell politics and funding initiatives: "A key lesson so far has been that low profile efforts seem more effective. Because Proposition 71 dealt with such large sums of money, it became a national, if not international, issue and attracted significant opposition ... In some states, there is no money involved at all. ... efforts in Missouri and Kansas that would do nothing more that write explicit language into state constitutions allowing private companies to conduct stem cell research. In Missouri she said, there was actually suggested legislation that would have barred residents from receiving therapies developed with stem cells, even if they were pioneered elsewhere."


Turning Stem Cells Into Tissues

The MIT Technology Review has a good piece on the fundamentals of regenerative medicine: "Biologists dream of the day they can take a stem cell and create any of the body's cell types, producing pancreas or liver tissue that doctors could use to aid a failing organ. ... If we want to take stem cells and convert them into something useful - neurons to treat Parkinson's disease, or insulin-producing cells to treat diabetes - we need to learn a lot about what makes a cell a neuron or a pancreatic cell ... The cell is a machine. Though we know the genes and proteins in a cell, we don't know how the machine works. ... Scientists would ultimately like to create a complete wiring diagram of the stem cell's regulatory circuit."


Idea Futures for Radical Life Extension

The productive use of exchanges for idea futures, a form of prediction market, is an idea that has not yet garnered the support it deserves. Consider it to be like derivative equity markets, only with ideas, bets and bold declarations in place of stocks. The predictive performance of diverse collections of people with money on the line is, on the whole, pretty impressive - which suggests that if you are onto something big and want to get the word out, then prediction markets are a better way to do it than most other methodologies that spring to mind. All it will take is some bright spark to figure out the right business model and idea futures exchanges will be everywhere. This, I think, will be a good thing.

While healthy prediction markets exist for all sorts of blandly popular things - politics and sports, for example - there seems to be a lack of initiatives for idea futures. Nonetheless, if you wander through the contents of the medicine and biotechnology section at the Foresight Exchange - a system that is more game-like, as it doesn't use real money, but rather people play for a score - you'll find some traded ideas relating to radical life extension, physical immortality and the MPrize for anti-aging research:

I suspect that the running claim percentages are an indication that removing money and profit from the idea futures equation leads to overestimation - or that this small market suffers from pro-technology, pro-life-extension selection bias due to the sort of folk more likely to take part. You should explore the exchange and take a look for yourself, however.

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Evolution and Calorie Restriction

Via PubMed, an interesting, if highly speculative paper on the evolutionary origins of the health and longevity benefits of calorie restriction: "An appreciable alteration in climate occurred between 2.0 and 1.5 million years ago, a juncture at which one hominid lineage (Paranthropus) went extinct. ... the Homo lineage responded to its marginal dietary repertoire through internal means, centering on metabolic suppression. It is herein hypothesized that this adaptive metabolic alteration, enacted in response to ecologically imposed caloric restriction, produced the defining morphologic attributes of Homo and enabled the evolutionary success of the human species. Among the implications of this line of thinking is that modern humans may be particularly sensitive to the deleterious effects of excess energy intake and, concomitantly, particularly amenable to the ameliorative effects of caloric restriction."


Type 2 Diabetes and Related Items

Two recent articles on the treatment of type 2 (age-related) diabetes make for an interesting contrast when read together.

Strong gene-link to type 2 diabetes revealed:

The researchers first isolated the gene variant while studying 2000 diabetes and control patients in Iceland. They found one occurrence of the specific gene variant in 50% more diabetes sufferers than in those free of the disease. They then replicated the findings in tests on people in Denmark and the US.

"This discovery sheds new light on the biological causes of the disease," Stefansson says. "Importantly, virtually all of this risk can be captured by looking at a single-letter change in DNA - ideal for the development of a genetic test for assessing individual risk and developing more personalised and effective prevention strategies.

He says the team is pursuing the development of diagnostics and new drugs for type 2 diabetes.

3-week Diet/exercise Study Shows 50 Percent Reversal In Metabolic Syndrome, Type 2 Diabetes:

The study shows, contrary to common belief, that Type 2 diabetes and metabolic syndrome can be reversed solely through lifestyle changes," according to lead researcher Christian Roberts of University of California, Los Angeles.

"This regimen reversed a clinical diagnosis of Type 2 diabetes or metabolic syndrome in about half the participants who had either of those conditions. However, the regimen may not have reversed damage such as plaque development in the arteries," Roberts said. "However, if Type 2 diabetes and metabolic syndrome continue to be controlled, further damage would likely be minimized and it's plausible that continuing to follow the program long-term may result in reversal of atherosclerosis."

While a regenerative cure for type 2 diabetes would be wonderful, this is a condition that most people could avoid, if they just took the right steps. There are more than enough age-related medical bugbears waiting in the wings of later life without going out of your way to add more; if you'd like to make it into the era of working anti-aging medicine - capable of repairing the cellular damage of aging - with both your savings and health intact, taking good care of yourself in the here and now is an excellent plan.

While we're thinking this way, I should point out another article of interest:

THE Government is backing North-East scientists in their efforts to identify how diet can affect ageing. Research has shown that the right nutrition is not only important for everyday life, but also has a major impact on the way in which humans age.

Scientists at Newcastle University have been asked to find out exactly how foods such as fresh fruit and vegetables are so beneficial in combating toxic agents, and why foods such as those high in fats and sugars are so bad for long-term health.

The Government is funding a new 6.4m research centre at the Tyneside university to carry out the work. To be known as the Centre for Integrated Systems Biology of Ageing and Nutrition (Cisban), the institute will try to extend people's knowledge about food.

Professor Tom Kirkwood, who is an internationally known expert on ageing, heads the institute.

This seems like a generally useful thing to be doing, albeit no great step forward towards longer, healthier lives; it seems hard to imagine any outcome of this sort of research that will be more effective than calorie restriction, for example. As for so much of what goes on in aging research, there is the sneaking suspicion that we could be doing much more productive, directed work aimed at greatly extending the healthy human life span.

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Gene Therapy for Macular Degeneration

Genetic Engineering News reports on a small trial of a new gene therapy: "An adenoviral-based vector containing the gene for human pigment epithelium-derived factor (PEDF) showed evidence of being able to stop disease progression when injected directly into the eyes of patients with neovascular age-related macular degeneration, according to the results of a phase I clinical trial." The positive effects were modest - at this stage in the development of gene therapies, scientists are delighted to obtain modest benefits with no accompanying issues or problem. "The results from the Campochiaro et al. study are extremely encouraging as there were no serious adverse events or dose-limiting toxicities through the highest dose."


Stem Cells, Peripheral Vascular Disease

The Saturday Evening Post takes a look at ongoing work in stem cell medicine: "To administer, we basically inject the cells, or the mononuclear cell fraction containing a subpopulation of progenitor stem cells, right into the calf muscle of the affected leg that has insufficient blood flow. In the future, we plan to grow the cells in culture and increase the number of endothelial progenitor cells before injecting. Right now, we have strict limitations on what we can do from the FDA, because this is the first such study in the United States. There is evidence the injected progenitor ceils directly incorporate into new capillary beds and produce the necessary protein messengers - so-called cytokines - that induce existing blood vessels to grow."


More On Exercise and Neurodegeneration

From the New Scientist, and just to drive the point home, another article on exercise and rates of neurodegenerative disease: "Regular exercise may reduce the risk of dementia and Alzheimer's disease in the elderly by as much as 40%, according to a new study. And the effect is even more pronounced for those who are more frail ... the biological mechanism behind the results is unknown, but that it may result from exercise causing a reduction in vascular disease. ... It could be that these people are still developing plaques [deposits in the brain which cause Alzheimer's] but exercise is stopping them from having strokes - so they are not showing clinical symptoms of dementia."


Therapeutic Cloning Confirmation

Good groundwork is reported in a Newswise release: "Scientists generally agree that all cloned animals are biologically flawed. But they don't agree about what that means for stem cells derived from cloned embryos, the basis for therapeutic cloning. ... Also known as somatic cell nuclear transfer, therapeutic cloning is a promising approach to create individually customized cellular therapies for treating certain disorders. Demonstrated in mice but not in humans, it begins with stem cells derived from a cloned embryo. But if cloned embryos can't produce normal organisms, how can they produce normal stem cells? Analyzing the complete gene-expression profiles of both cloned and fertilization-derived stem cells in mice, [scientists] now have concluded that the two are, in fact, indistinguishable. ... This paper demonstrates clearly that it doesn't matter if a stem cell has been derived from a cloned embryo or from a fertilized embryo."


Mathematics of Physical Immortality

Jay Fox is blogging more regularly once more. The first part - the introduction - to an essay on the mathematics of physical immortality is up at Longevity First: "Living longer, even just a few years, could mean the difference between having access to a breakthrough medical treatment that will add 10-20 years to your life, or not having access to it. And that 10-20 years could be the difference between having access to the next big breakthrough, adding even more decades to your life ... In other words, losing 20 pounds and exercising three times a week could be all it takes [aside from advances in medicine] to add 30 or 50 years to your lifespan. In fact, if medical progress is fast enough, losing those 20 pounds could be the difference between living to 65 or living to 165, or even 1,065." Staying ahead of the curve of medical advances is also known as actuarial escape velocity.


Two Interesting Immortality Institute Discussions

I thought I would point your attention to a pair of interesting discussion threads presently ongoing in the Immortality Institute forums. Firstly, commentary by S. Jay Olshansky and others on a very rare developmental abnormality:

I came across this story a few months ago as well, and didn't believe it. A colleague decided to check into it -- it is indeed a true story, and I agree with you that it is certainly a very interesting phenomenon. I actually have seen a picture of the girl with her grandmother and siblings as well as a series of pictures during most of her life. Her pediatrician has been contacted for a life history; someone is looking at her telomeres; and an inquiry has been made about her mental development. The price to pay for her apparent arrested physical development is an arrested mental development. In the one other case of this kind that we know of, the girl died at about age 15 because of problems with her intestines, and she too faced severe problems of mental development. Nevertheless, to have a teenager exhibit the phenotype of a 4-year old is astonishing. I'm encouraging my colleague to write up the details of his work and publish it in a high profile journal -- to our knowledge we have not seen this as a recognized syndrome. It may have considerable relevance to research in gerontology. Hopefully you'll see more on this by the end of this year.

Developmental abnormalities may or may not shed light on aging, but at the present time it's still very important to grasp at any such mutations for their potential to provide a short cut through some portion of genetic science. Studies of progeria recently led to important advances in understanding, for example.

The second discussion of interest can be found in John Schloendorn's LysoSENS thread; he's providing updates of experiments on the soil samples sent in by volunteers, seeking non-toxic bacterial enzymes capable of breaking down damaging age-related chemical byproducts.

Earlier than I had dared to hope, we have obtained two new cultures that efficiently degrade one of our major targets, 7-ketocholesterol. They reproducibly deplete it from the medium within 10 days, which is more rapid than anything we have seen before, and utilize it as a growth substrate. Now the fun will start to isolate the bugs from the mixed cultures and take them apart. One of the cultures originated from a mixed inoculum containing the early samples submitted by QJones and Mind and a few other donated garden samples. We cannot tell in which submission precisely they originated, since we pool several samples for efficiency. (you have to submit a couple of them to get your own exclusive pool ;-) The other culture came from cemetary samples collected by ourselves. Both cultures seem equally efficient, look alike and it could be the same organism.

Eternal thanks to our soil donors who made this wonderful result possible, together.


please keep in mind that failure can come in many ways. The organisms might not grow on plates, compromising isolation, the genetics might not work out as we hope, the enzyme may be toxic and so on...

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The Instant-Death Third Rail of Grantsmanship

Reseacher Rafal Smigrodzki, a member of the mitochondrial protofection team, made the following comment on the Gerontology Research Group mailing list. He is referring to a recent New Scientist article on mitochondrial research and aging:

Just to do some damage control:

The article might give the impression that the applications of protofection as a treatment of aging might be imminent - but, as I was at pains to explain to the reporter, Gencia corporation is going to use the technique first in classical mitochondrial diseases, and we are definitely not in the business of making a cure for aging. A "gleam in our eye" means that if (and that's a big if) things work out well with classical mitochondrial disease, then maybe in ten or fifteen years it could lead to wider applications, in the treatment of the mitochondrial aspects of some age-related conditions.

"The cure for aging" is the instant-death third rail of grantsmanship and we stay away from it.

This, I think, compactly illustrates the most fundamental problem facing meaningful anti-aging research today - addressed from a slightly different perspective in an article over at the Longevity Meme - which is that most sources of funding will not even consider devoting minimal resources to serious, well-backed exploratory work, let alone anything more substantial. They have completely closed the door on any form of responsible work on repairing or preventing age-related cellular damage, on intervening in the aging process. So it shouldn't be all that surprising that comparatively little work is being done to challenge the status quo; that work requires funding, and obtaining it while sticking to your guns is certainly not the path of least resistance.

If you want to stay in the conventional funding game, you can't even talk about therapies for degenerative aging; you must disavow any potential anti-aging application of your work, and stick to working towards therapies for specific conditions. This all ties back into last week's post on strategies for developing large-scale funding for directed anti-aging research - funding required for rapid progress towards far longer healthy life spans and the first stages of actuarial escape velocity.

The primary goal of healthy life extension advocates and activists must be to break out of the present poor situation and move into an era of support, understanding and funding for scientific efforts to cure aging.

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Antlers as a Path to Organ Regrowth

(From Medical News Today). A vast range of fascinating adaptations to the biochemistry of healing and growth can be found in the animal kingdom. Some scientists are trying to bring lizard-like regenerative capabilities to humans, while others have found a possibly shorter path to useful medical technology: "Many lower animals such as newts can renew damaged parts of their bodies but antler growth is the only [natural] example of mammals being able to regrow large complex organs. ... The research suggests that unlike the regenerative process in the newt, antler growth does not involve reversal of the differentiated state but is stem cell based. ... If we can understand how deer have adapted the normal means of development, cell renewal and repair to redevelop a complete organ, it may be possible to achieve the same outcome in damaged human tissues."


On Information Infrastructure in Biotechnology and Medical Research

The present information infrastructure in biotechnology and medical research is quite simply not up to the task at hand - dramatic advances in our ability to generate data have outstripped the development of processes and tools to make that data useful. This problem manifests itself in the form of lost opportunities, duplicated or wasted effort, and missed answers. In other words, progress in medical science is nowhere near as fast as it could be, just using the technologies of today. Fortunately, this truth is no great secret: everyone knows, and resources are being directed into the development of solutions.

On the process side, we have the move towards open access journals and other forms of open publication. The Public Library of Science is shifting it's weight into clinical trial data, for example:

Clinical trials - and particularly randomized trials - are critical in delivering reliable evidence about the efficacy of an intervention. Clinical trial data can also provide important information about the potential adverse effects of treatment. Currently, not all trials on human participants are reported in the peer-reviewed literature. PLoS Clinical Trials aims to fill this gap. The journal will broaden the scope of clinical trials reporting by publishing the results of randomized clinical trials in humans from all medical and public health disciplines. Publication decisions will not be affected by the direction of results, size or perceived importance of the trial. As an open-access journal, all articles published in the journal will be immediately and freely available online.

I see the main benefit to open publication strategies being the platform they provide for open-source models of development in automation, tools and processes of data management within the scientific community. If the data is free, the only cost to building a better utilitization of that data is your time ... and we've seen that this situation produces very impressive end results in software development. The closed journals - and their business models - are a roadblock to that sort of progress, and I think that roadblock is becoming a real problem in the information-rich fields of biotechnology and medicine.

On the technology side, a range of tools are under development. The informational side of biotech looks a lot like the open source movement of ten years ago - many competing standards, lots of good ideas and a real froth of software. An example of the sort of tools I'm talking about is the work of Butte and Kohane:

"Nearly 100 different diseases have been studied using microarrays, spanning all of medicine. This is a new way to explore this type of data. We can study virtually everything that's been studied." Butte is the first author of the study, which is published in the Jan. 6 online issue of Nature Biotechnology.

The advance comes with a caveat, however: clinically useful nuggets will be buried under the avalanche of data inundating international repositories each year unless scientists come up with a way to better classify their experiments and results.

"Libraries figured out a long time ago how to classify items using the Dewey decimal and other systems," said Butte, who estimates that the contents of the databases are more than doubling each year. "We need to write software now that will help scientists assign the proper concepts to each experiment."


Butte and his Harvard co-author, Isaac Kohane, MD, PhD, used computer programs to automatically categorize the tens of thousands of microarray experiments in a single database based on the terms, or concepts, used by the submitter to describe the experiment. They then looked for findings shared by several experiments with similar concepts, such as tissue type, for example. Comparing results from many similar experiments allowed them to identify correlations that may not be statistically significant in just one experiment.

If progress in biotechnology and medicine is to continue at the present healthy pace - especially in very complex problems that span many comparatively isolated fields, such as addressing age-related degeneration - then the research community must successfully deal with the problem of data management.

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Understanding Neurogenesis

If scientists are to apply the methods of regenerative medicine to age-related degeneration in the brain, much more care and knowledge will be required than for, say, the heart - the consequences of various subtle problems and failures are so much more serious. Here, Scientific American takes a brief look at one step forward in relevant research: "brains continue to produce new neurons throughout life, helping create new neural networks. This neurogenesis only takes place in a few specific areas, such as the area in which the brain and spinal column meet. The new cells, however, can migrate throughout the brain and turn up as far away as the olfactory bulb - a cluster of nerve cells at the front surface of the brain responsible for the sense of smell. A recent study in mice has revealed that these neurons make the long and complicated journey by going with the flow of spinal fluid circulating in the brain."


Investigating Inflammatory Arthritis

A number of different strategies for dealing with arthritis are presently in the research queue. Medical News Today reports on hints of yet another potential methodology: "Mice lacking [the protein] T-bet had markedly reduced joint inflammation and T-bet-deficient mice without T or B cells were essentially resistant to disease. They also found that transfer of normal dendritic cells that make T-bet, but not T-bet-deficient dendritic cells, into mice unable to make T cells, B cells or T-bet, was able to cause inflammatory arthritis. The study shows that the ability of dendritic cells to secrete proinflammatory molecules and to prime T cells to initiate an immune response is compromised in the absence of T-bet. T-bet could provide an attractive new target for therapy in inflammatory arthritis."


Beware of Russians Bearing Stem Cells

I've noted the sorry state of affairs in Russia, insofar as disreputable stem cell medicine goes, in the past. Andrew Lynch recently pointed me to a BBC article on that topic - little change, it seems.

Dr Ramil Khabriev, the head of Russia's Public Health Agency, is alarmed by the rapid growth in their use in Russia because they could have serious side effects.

"It's not only me, many scientists around the world are worried, because nobody knows what the consequences of using stem cells are," he says.

"The aim is to inject the cells into your body where they transform into any type of cell you need.

"But they could cause cancer. There's a very big risk of that."

The article covers obviously fraudulent - and quite probably dangerous - beauty salons as well as medical organizations that are engaged in more responsible work. It's a great pity that so much of this activity in Russian, China and elsewhere in the world is conducted without producing data that could help advance the first generation of stem cell research - but such is the way things go.

While folk certainly should have the right to choose their own risks and expenditures in life, in health as for everything else, it would seem wise to wait for stem cell science and the development of regenerative medicine to advance - if you are in a position to do so.

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Better Inkjets For Tissue Engineering

Inkjet printing technology is in the process of adaptation to tissue engineering - we've been hearing about this for the past year or two. A part of this adaptation is finding ways to improve those aspects of this technology that are substandard for the new use. From PhysicsWeb: "The advantage of this method compared to conventional ink-jet technology is that it can create droplets as small as just a few microns across from needles with diameters as large as hundreds of microns. ... The technique may have huge potential for patterning predetermined 2D and 3D biological architectures, such as tissues and organs, at the micron and nanometre scales." A number of organs are very complex at these scales - this is a promising piece of groundwork.


Hedgehog Signaling, Aging

Via Forbes, news of an interesting advance in our understanding of biochemistry: "The finding suggests that drugs that target this hedgehog (Hh) signaling pathway -- a set of genes involved in determining the destiny of many cell types -- may prove effective in treating obesity, diabetes, osteoporosis and lipodystrophy, a disease characterized by an absence of fat. The new insight into the Hh pathway may also help explain common traits associated with aging, the study authors said. ... As we age, two striking things tend to happen almost across the board - our bones become thinner and we gain fat ... Our findings are consistent with the idea that hedgehog signaling may diminish as we get older. Drugs that stimulate the pathway could possibly help to reverse or prevent this trend, building stronger bones while reducing fat."


Mitochondria and Aging

The New Scientist takes a look at mitochondria and their role in degenerative aging: "Pinning down the molecular changes that underlie the ageing process is not easy. But it has long been suspected that mitochondria, the energy-generating structures within almost every cell of the body, play a key role. And in the past couple of years, researchers have produced strong evidence that this is indeed the case, that the decline of mitochondria determines when our bodies begin to crumble." A number of groups are making progress in the development of biotechnologies capable of either repairing, moving or replacing damaged mitochondrial DNA. This is encouraging for those of us whose future health and longevity depends on the outcome of this research.


Nanomedicine Via Nanodot

At times, it's hard to keep up with the switching of hosts and locations for all of the worthwhile blogs out there. I had not noticed that Nanodot is now hosted by the Foresight Nanotech Institute, for example - a move that makes perfect sense. Two recent posts on the future of nanomedicine should be of interest to advocates and supporters of healthy life extension research:

Time estimates for nano developments 2008-2021:

The 50% median date estimate from "experts and knowledgeable" for sample statements among the 20 tested are as follows:

2008: Nano-agents for analysis inside cells
2013: Nanotools for manipulation inside cells
2015: Self-repairing in artificial systems
2018: In vitro construction of human organs
2021: Nanomachines inside the body

If you're of the view that it takes about ten years to produce a raft of worthwhile, widely commercialized products from a new advance, that timeline looks very Kurzweilian - 2025 for mature technologies to repair any genetic or biomolecular defects we can characterise sufficiently well, and 2035 for blue sky nanomedicine to regrow, enhance and repair whatever faults, diseases and conditions come to mind. To my mind the most important limits to progress are going to result from complexity management - from the time taken to sufficiently understand the biological systems we will be manipulating, and the challenges inherent in organizing, assimilating and using vast amounts of information.

Nanosurgery journal article by Freitas

We envision biocompatible surgical nanorobots that can find and eliminate isolated cancerous cells, remove microvascular obstructions and recondition vascular endothelial cells, perform 'noninvasive' tissue and organ transplants, conduct molecular repairs on traumatized extracellular and intracellular structures, and even exchange new whole chromosomes for old ones inside individual living human cells

If you find Robert Freitas' presentations interesting, you should take a look at a recent interview, an article on the cost of aging and death, and his large body of work on the foundations of advanced nanomedicine.

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Calorie Restriction and the Heart

Now that funding is coming into calorie restriction studies, more detailed examinations of the health and longevity benefits have been forthcoming. EurekAlert provides one such example: "Studying heart function in members of an organization called the Caloric Restriction Society, investigators at Washington University School of Medicine in St. Louis found that their hearts functioned like the hearts of much younger people. ... Ultrasound examinations showed that the hearts of people on caloric restriction appeared more elastic than those of age- and gender-matched control subjects. Their hearts were able to relax between beats in a way similar to the hearts in younger people. ... This is the first study to demonstrate that long-term calorie restriction with optimal nutrition has cardiac-specific effects that ameliorate age-associated declines in heart function."


The Latest Annals of the NYAS

The latest Annals of the New York Academy of Sciences looks to be of interest to healthy life extension advocates and supporters, with section titles such as "The Earthly Cage of Aging: Can We Escape from It? Theories, Concepts, Views, Proposals" and "Biomolecular Interventions Suitable for Interpreting, Preventing, or Curing Aging." Take some time to wander through. Interestingly, Ronald Klatz of the American Association of Anti-Aging Medicine (A4M) - an organization I've taken to task in the past - has a paper in this issue outlining his present public position on anti-aging medicine:

Anti-aging medicine is a medical specialty founded on the application of advanced scientific and medical technologies for the early detection, prevention, treatment, and reversal of age-related dysfunction, disorders, and diseases. It is a health care model promoting innovative science and research to prolong the healthy life span in humans. As such, anti-aging medicine is based on principles of sound and responsible medical care consistent with those applied in other preventive health specialties. Because it embraces the use of biomedical technology, anti-aging medicine offers a hopeful model of health care in which healthy human life spans of 120 years and longer may be achieved - if we employ anti-aging therapeutics today, and encourage the continued expansion of biomedical technologies to prevent, treat, and cure diseases.

I have thought - and still think - that this is a positive direction for A4M in the long term, provided that the actions match the words. Now if they could just ditch their support of and association with the shady, unhelpful segments of the "anti-aging" marketplace...

You might recall last year's publication of work by Valter Longo advancing his ideas on the degree to which aging is programmed (versus, say, an accumulation of cellular damage leading to various unprogrammed failure modes - simple decay, in other words). Here, Longo and a fellow researcher are trying to tie - tenuously, I think - concepts of programmed aging to the production of damaging reactive oxygen species (free radicals):

Many of the steps of programmed cell death are shown to be common for yeast and animals, including mammals. In particular, generation of the mitochondrial reactive oxygen species (ROS) is involved in the suicide programs. Aging of higher animals is accompanied by an increase in damage induced by mitochondrial ROS. Perhaps prevention of such damage by scavenging of mitochondrial ROS might slow down or even switch off the aging programs.

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Theory in Gerontology

You can read an interesting excerpt from the new Cambridge Handbook of Age and Aging online: "The field of gerontology has accumulated vast amounts of data over the past several decades, creating a goldmine of potential theoretical knowledge. Yet explicit theory development has lagged - prompting some to observe that gerontology remains data-rich and theory-poor ... Several factors may have impeded theoretical progress in gerontology [including] the difficulty of crossing disciplinary boundaries in order to create multidisciplinary explanations and interpretations of phenomena of ageing." This is a point often made by biomedical gerontologist Aubrey de Grey - biomedical research is very much in need of cross-field pollenation, analysis and synthesis.


Weight and Risk: A Reminder

From Medical News Today, another study to reinforce the damage done of being overweight: "Of the 17,640 participants who had survived to age 65 and older, those who were overweight, and particularly those who were obese earlier in life, had significantly higher risks of hospitalizations for and death from heart disease and diabetes in older age compared with persons of normal weight with similar other cardiovascular risk factors at the beginning of the study. ... Results of the study showed that having a normal BMI in young adulthood and middle age confers significant health benefits at all levels of traditional risk factors." While the future of medical technology is bright, it would be foolish to expect it to arrive soon enough to save you from the consequences of today's negligence.


A New York Stem Cell Institute

From the Business Review: "The state Assembly has approved legislation creating a New York State Institute for Stem Cell Research and Regenerative Medicine. The measure appropriates $300 million from the state's Health Care Reform Act over the next two years to foster research into chronic regenerative diseases." I have much the same commentary on this as on Proposition 71 and the California Institute for Regenerative Medicine - it's hard to say what hinderances to serious research were slipped into that bill, deliberately or otherwise. Over a decade or more, regulation can easily cause far more economic damage to scientific progress than the tax dollars disbursed by this legislation.


A Profile Piece on Michael Rose, Aging Research, Radical Life Extension

The Orange County Register recently published a profile article on the work of biologist Michael Rose, author of "The Long Tomorrow." Some obnoxious free registration acrobatics might be required to view it, or alternately, if reading this post within the next few days, you can jump to Google News and click right through. The article is notable for being the first mainstream piece I've seen in which Rose puts figures to his thoughts on the timescale for radical life extension:

In 400 years, people will live to be 1,000. Michael R. Rose knows his prediction sounds ridiculous. To most people, it probably seems unbelievable. But, after working on aging for 30 years, the UC Irvine professor and scientist says we'll be playing golf in our 900s.


"You can't be in the NFL anymore. You can't be Britney Spears," Rose says. But you can be middle-aged for a long, long time, if that's what you want.

"People will look back on the 20th century as one of the last ages where you could fall apart without anybody doing anything about it," Rose says.

"I figure this project will go on for 200 years. I don't expect to be around."

Needless to say, I think there's a good chance that we can do much better than this prediction, or I wouldn't spend as much time as I do on advocacy in support of longevity research. The key concept to consider when thinking about the future of life, health, medical technology and longevity is actuarial escape velocity - every round of improvements brings more healthy years in which to await (or help to advance!) further improvements. Thus comparatively modest initial gains in technology and life span can be the first step on a road that is a long as you'd like it to be. This is far from a universally accepted idea, but it makes sense to me.

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DNA Repair: Inhibition and Improvement

Via the Cambridge Evening News, a piece on progress towards therapies for cancer - and potentially aging - based on manipulating the biochemical mechanisms of DNA repair: "The ideal anti-cancer drug will hit the cancer cells much harder. Cancer cells are more reliant on DNA repair than other cells, which makes it possible to target them more accurately. Of the three compounds we have in clinical trials, the one we are most excited about is the DNA repair inhibitor, PARP ... DNA repair mechanism also controls ageing, and how it works slows down as you get older. Making human cells repair DNA better could make you live longer, we are just at the tip of the iceberg with all this."


The Report on Korean Stem Cell Research

Since I commented on this episode of faked science from the laboratory of Woo Suk Hwang a few weeks ago, I should probably point you towards the summary of the investigative report. It goes some way towards showing where science presently stands on the road towards personalized regenerative toolkits and the reliable manipulation - and creation - of embryonic stem cells.

I should repeat the thesis of my last post: all too many people look at events of this sort and see failure of the scientific system. On the contrary, this is the sign of success - a high-profile example of the ruthlessness of the scientific community when faced with misrepresentation. No-one stands above the scientific method; careers are torn down and scientists ostracised regardless of status when fraud is uncovered. A pity that policitians do not reliably suffer the same fate for their misdeeds.

However, that the publications are fabricated alone mandates a severe penalty by the academia. These individuals cannot be regarded to represent science in Korea. We have numerous well-qualified researchers whose works are globally recognized, and we also have a world-class research capability in biological sciences that will ensure a successful partaking in the field of stem cell biology. Our judgment is thus that the scandalous case of Woo Suk Hwang and cloned ES cells will not have a large impact on the effort of the scientific community in Korea. Rather, we are certain that this learning experience will be a stepping stone for better execution and management of scientific research and contribute to scientific advancement in this country. The young scientists who courageously pointed out the fallacy and precipitated the initiation of this investigation are our hope for the future.

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Tengion's Research Proceeding

(Via the Business Journal). Tengion is representative of a number of efforts to commercialize the first steps in tissue engineering; building comparatively simple, smaller organs such as veins and bladders. It sounds like things are moving ahead: "Wake Forest University has signed a 'multiyear, multimillion-dollar' deal with a private firm to fund research and commercialization of Dr. Tony Atala's work in regenerative medicine. ... Under the new contract, Tengion will fund research projects that focus on blood vessel and other vascular systems and urinary organs. Tengion will receive an exclusive worldwide license or option to develop the technology that results from the research." Now that venture money is involved, with its own sense of haste and profit, we should expect to see real products emerge over the next few years.


More Stem Cells Versus Heart Damage

A good European study is reported at EurekAlert: "a major breakthrough in the treatment of patients with acute myocardial infarction. Their research shows that the administration of a patient's own stem cells has a significant positive effect on the heart's recovery: in the patients studied, the size of the infarct was clearly reduced. The use of stem cells appears to be safe, and to date no side effects have occurred that can be attributed to the stem cells. ... a clear global improvement in function was found in the sub-group of patients who had been afflicted with the most serious infarctions. Moreover, the reduction of the size of infarct was significantly greater in all patients in the 'stem cell group' and correlates with a better preserved regional left ventricle function." The use of a patient's own stem cells is a very promising direction for first generation regenerative medicine.


On Growth Hormone

From MSNBC, a mostly useful repetition of common sense and facts on the medical use of growth hormone, a staple of the less reputable end of the "anti-aging" marketplace: "if a doctor, clinic or website promises you that they have a non injectable product that will restore your growth hormone level to that which you had when you were young, beware. Products available without prescription are imposters and have no effect. Those that are prescribed and injected are expensive, and we don't have the long-term studies that give conclusive proof that they work." Caveat emptor! But I don't agree with centralized regulation - let people make their own informed choices when it comes to their lives and their bodies, provided they're also responsible for the cost of consequences.


Autoimmunity Versus Neurodegeneration

From recent Scientific American article: "In 2002 a clinical trial of an experimental Alzheimer's vaccine was halted when a few patients began experiencing brain inflammation, a result of the immune system mounting an attack against the body. Now some researchers claim that inducing a mild autoimmune reaction could actually protect the central nervous system from a spectrum of neurodegenerative conditions, from glaucoma and spinal cord injury to Parkinson's and Alzheimer's disease. ... Too much autoimmunity causes brain disease, but too little may exacerbate the gamut of neurodegenerative conditions ... The evidence is mixed, however. We get what the conventional wisdom would expect: we get more problems ... The discrepancy probably results from subtle differences in the models employed, which implies that the effect is not robust enough to treat spinal cord injuries."


On Strategies for Large Scale Funding of Longevity Research

Elixxir is a flashy "anti-aging" consultant - one part calorie restriction to two parts unproven advice and mysticism, as I understand it, which would place him about on a par with Dr. Weil insofar as scientific backing goes - who also dabbles in advocacy for government funding of longevity research. Calorie restriction isn't rocket science; while responsible diet consultants certainly have their place as a luxury item, I'd suggest reading around online and picking up a copy of the Longevity Diet prior to paying anything else to anyone else. Caveat emptor and your own research are good philosophies to hold to.

In response to the recent 60 Minutes segment on radical life extension, Elixxir has assembled his critique of the methodology of the Methuselah Foundation and biomedical gerontologist Aubrey de Grey. Skipping over the florid and self-aggrandizing portions, he makes a few arguments that have shown up over the past few years from those who object to the MPrize as a vehicle for improving the presently sad state of serious anti-aging research. In particular, I'm thinking of the suggestion that petitioning government for funding should be the primary activity of healthy life extension activists and advocates.

Yes, prizes don't hurt. But history shows what really works -- a hundred times, a thousand times more powerfully -- is state funding for research.

The Nobel Prize is as good as it gets for prizes. Yet most scientists or grad students who choose to go into a field or line of research don't do it because of the Nobel Prize, because even though it offers a prize of a million plus dollars, and a lot more prestige indeed, it is not a sure thing. It's not something that can sustain a researcher economically over the years. History clearly shows that what does greatly encourage grad students and even established researchers to go into a new field or new line of research is state funding, lots of state funding.

The examples of this fact -- that it is state funding and not prizes which really spurs research and breakthroughs -- are abundant and undeniable. The Manhattan Project. The Apollo Program. The National Institutes of Health. National Cancer Institutes.

Even if the Methuselah Prize goes up to 10 million, it will still fall far short to achieve our monumental goal! What is needed is state funding, and what opens up the spigot of state funding so it gushes out to the tune of hundreds of millions, and even hundreds of billions of dollars? Political pressure, lobbying, and grassroots activism.

I think most regular readers will know my objections to involving the government in anything by now, but de Grey - who is not libertarian - also sees this as a poor strategy. To him, parallels drawn with past government programs initiated through activism from the scientific community and wider public, such as cancer research and AIDS research, do not hold in the case of aging. This is illustrated by the lack of progress in building an analogous goverment-funded research infrastructure for longevity research over the past few decades.

de Grey responds personally to almost everyone who contacts him - a habit he will be forced to give up all too soon by the constraints of time and an ever-growing public profile - and his email response to Elixxir, also posted in the Immortality Institute thread on the topic, outlines his opposition to petitioning government:

Many thanks for your thoughts. I agree wholeheartedly with most of what you say, but I believe you have overlooked a couple of points and that these points invalidate your conclusions.

First, you are wrong to suppose that a campaign of the sort you describe has the faintest hope, as things stand, of influencing public policy on the funding of life extension research. The problem is that governments will not fund something unless they perceive that it will win them votes, and currently society is overwhelmingly in what I've termed a pro aging trance, whereby they resolutely persist in believing that serious life extension is not only impossible but is also undesirable on account of the social upheavals it would cause. Thus, of the four communities that might make a difference to the pace of the relevant research, the one which there is no point whatever in directly lobbying is the government. Lasker didn't have this problem -- there was no pro-cancer trance. 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. Politicians don't listen to lobbyists -- they listen to voters and voters' representatives.

Read the rest; it's a good insight into present Methuselah Foundation strategy. The end goal is of course the development and commercialization of working anti-aging therapies, capable of repairing age-related cellular damage, but the most important requirements for that goal are widespread understanding and support and large-scale funding.

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Insight Into the Life Extension Foundation

Brief summaries never manage to convey the interesting subtleties and history of an organization, but a brief summary of the Life Extension Foundation (LEF) is probably in order here. The LEF is one of the half-dozen or so more responsible vitamin and supplement suppliers in the healthy life extension community - which is not to say you should take anything at face value without doing your own research. Vitamins and supplements, as for so many other things in life, can form a deep - and ultimately wasteful - rabbit hole to vanish down if you fail to keep a sense of proportion. In any case, this large, visible business is the money-generating engine that supports efforts to provide health and longevity optimization advice to LEF members and the public, as well as fund a modest amount of scientific research. Calorie restriction studies and cryonics research are amongst the funding recipients. In other words, the LEF is the archetypical old school life extension venture, an outgrowth of the past generation of the healthy life extension community.

Two recent articles from Life Extension Magazine provide insights into the mindset and goals of those steering the LEF.

Death by Neglect:

The people in the photograph on this page all had a common problem. Despite being the most powerful group in the world at the time, they did little to protect their own lives. As a result, they all died.

Before the 1960s, few people even thought about the idea of radically extending the human life span. As medicine evolved, however, people began to realize that the length of their own lives is highly dependent on the rate of scientific progress. Those in the federal government who control the funding of medical research have a great deal of influence over the extent to which scientists are able to challenge aging and death. Regrettably, government leaders have paid scant attention to protecting Americans from the ravages of aging.

To me, as a libertarian of the minarchist persuasion, the folk running the LEF have a fascinating perception of government. You have to read up on some of the backstory here - the founders were stepped on by the federal government back in the early 1990s in a typically heavy-handed, unnecessary and underhanded way. The LEF won in the end, a very unusual outcome, but it certainly can't have been any fun at the time. For those of you who view government as benign, this should be an eye-opener - but this sort of abuse (and a thousand other examples from the FDA) is the predictable result of a lack of accountability, i.e. an entirely usual state of affairs in a Western style democracy.

Despite this history, here we have an article that is supportive of the very government structures that lead to FDA abuse. The author simply bemoans the way in which past tax revenue was used - i.e. not to further the extension of the healthy human life span. In a way, it mirrors my comments on the use of resources by the past generation of healthy life extension advocates - the LEF founders amongst them. Is this an example of practicality in the face of structures you cannot tear down? You decide.

Life Extension's Visionary Plan to Conquer Aging and Death:

In 2035, it is apparent that major breakthroughs are on the horizon: gene therapies to prevent aging; intelligent nanorobots to repair dysfunctional brain cells; neurostimulatory therapies to regenerate organs and other body parts; young tissues developed from stem cells to rejuvenate life systems; and new technologies to improve vision, hearing, strength, intelligence, sexual prowess, and other attributes.

Unfortunately, it is also apparent that it will still take decades to fully implement these advanced breakthroughs, which will be too late for you. The thought has begun to cross your mind that your generation might be the last to face death before a greatly extended healthy life span becomes commonplace.


However, all is not lost. Suspended animation, an advanced technology that was perfected in 2030, is readily available at hospitals throughout the world.

LEF founder Saul Kent's long term vision, as for anyone in his generation interested in living very much longer lives, hinges on cryonics technology. For those of us young enough to live into the era of working anti-aging medicine - capable of repairing age-related cellular damage and thus achieving rejuvenation - cryonics is an important insurance policy. Are we going to make it? Will medical science advance rapidly enough? For older folk, cryonic suspension is the only viable alternative to the grave - and a great deal of work and funding is yet required to develop a thriving, healthy cryonics industry from the present small beginnings.

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Pro-State Transhumanism

In the Deseret News, a somewhat depressing look at early skirmishes in the war over who gets to control what you are permitted to do with your own life - including how long you are permitted to live. It's sad that it has come to this, that so many people pour resources in fighting for control of - and thereby supporting and sustaining - an increasingly dangerous and corrupt system. Consider this: in a truly free society of small government and rule of law, employees of the state would not have the power to block support and development of real anti-aging technologies, nor block your opportunity to amass wealth and purchase working anti-aging medicine. To live longer or not would be an individual choice; the only need for resources would be to develop the necessary medical technologies - not to defend your health and life from uncaring, over-empowered government employees.


Myths of Aging

Jay Fox refutes some of the myths employed by opponents of healthy life extension: "Here we see four of the same old fallacies exposed again: the Tithonus Error, Malthusian Doomsaying, the Lonely Old Man, and Logan's Run. ... As Harrell put it, 'the thought of outliving everyone they know is depressing.' I admit it is depressing, but it misses the rather obvious rebuttal: is this lonely old man the only person who will receive rejuvenation treatments? ... The thought of living to 300 may seem daunting. But ask yourself, are you ready to die in the next year? If you answered no, then you already have what it takes to live to 300. Next year, if you were in as good or better health than you are now, with as good or a better financial position, the answer to that question should not change: it should still be no. Ten years from now, if you could have even better health and more wealth, would you decide, 'You know what, I think this year is the year!'? Of course not."


Election Process Underway at the Immortality Institute

As Jay Fox notes, and I have been remiss in failing to point out, the election process is underway at the Immortality Institute - that most useful generator of better outrageous extremes in the public debate over healthy life extension.

Of the current board of directors, I, Jay Fox (jaydfox), am the only one who was not one of the original directors who founded the Immortality Institute. Kevin, Reason, Sebastian, and Kennetth have all been there from the infancy of ImmInst, alongside Bruce Klein (BruceKlein) and Susan Fonseca-Klein (chestnut). I am the newcomer, and I was encouraged into service because of my zeal, and my proliferative and thoughtful writings.

However, in the past year, many new faces have joined the ranks of the zealous, proliferative, and thoughtful at ImmInst. Many old faces have remained true to the cause, the mission to "conquer the blight of involuntary death". New advisors have been appointed, advising on issues such as cryonics and biotechnology. There are at least a dozen individuals I would feel proud to serve with on the board of directors, many of whom have already been nominated at least once already.

It's time for these fresh new ideas, perspectives, and leadership styles to help push ImmInst along.

As one of the present board members who is stepping aside, I must agree with this. I am a very busy person at the best of times, and in a small nonprofit like the Institute - or in any online, largely virtual organization like the Institute - it is very important that individual board members be energetic, proactive, driving forces. There are plenty who could do that far better than I simply by merit of having the time to devote ... meanwhile, I will no doubt be just as good a resource for the Institute as a member as I was while on the board. That, in and of itself, is a good reason to step down and let some new blood into the organization.

The Immortality Institute has successfully grown its membership and raised funds for a number of very useful projects over the past two years - including a book and film release. The founder, Bruce Klein, has built up a valuable network of contacts and donors within the healthy life extension community, a network that can be turned to enable future, more ambitious projects. The Institute forums are the largest and most active online transhumanist, pro-life-extension gathering - a watering hole and point of collaboration for advocates, enthusiasts, supporters, gerontologists, scientists and others.

So take this opportunity to take a look! Consider joining as a full member and participating in this election - the Institute is certainly doing its part to help bring the future of working anti-aging medicine closer, and thus ensure that you live a longer, healthier life. Repaying that favor with a little of your time and energy certainly couldn't hurt.

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Engineering New Mammary Tissue

A nice piece of work is reported by the Times: as a part of demonstrating their ability to isolate mammary stem cells, scientists have "transplanted one of these cells into the mammary fat pad of a living female mouse from which all breast tissue had been removed. The cell divided and eventually gave rise to all the normal types of cell found in the mouse breast, and the gland worked normally to produce milk. ... If the findings prove applicable to people, scientists hope to develop drugs that target abnormal breast stem cells to eliminate not only tumours but also the source tissue from which they arise. In the longer term, it may also be possible to use mammary stem cells to grow breast tissue for reconstructive surgery after a mastectomy." Researchers are clearly making progress in capabilities when it comes to stem cell science.


More Follicle Stem Cell Progress

We've been hearing much more about the multipotent stem cells found in hair follicles of late. Here, more from Medical News Today illustrates that the infrastructural and supporting work is proceeding apace: researchers "used sophisticated techniques to engraft human scalp tissue onto mice and then isolated and examined living human hair follicle stem cells. The authors identified a panel of marker proteins expressed on the surface of these elusive cells that can be used in future research to aid in their identification. They go on to note important differences between mouse and human stem cell markers. ... investigators can now readily extract and study very specific follicular cell types for the ability to regenerate hair and skin, with the hope of developing novel methods for treating skin and hair disease." Infrastructure is bland, but very important. Expect to hear more in the near future.


A Pity Some Feel the Need to Counterpoint

Let me direct your attention to a paper in the Annals of the New York Academy of Science entitled "Would Doubling the Human Lifespan Be a Net Positive or Negative for Us, Either as Individuals or as a Society? Point-Counterpoint":

There is a significant possibility that over the next few decades science will make discoveries of a kind that might allow the doubling of the average human life span, from roughly 76 years now to 150. This development would, for many, represent the realization of a dream: that of enabling people to live much longer lives than at present, holding back death, which has often been seen as an ancient, unbeatable enemy. It would also raise a large number of unprecedented individual and social problems: Would we really want to live to 150? Is such a goal ethical? What would this putative longevity do to our present social structures and arrangements? Would we get a better society or a worse one?

The helpful, positive, pro-healthy life extension points are provided by Gregory Stock. The doleful counterpoint is by Daniel Callahan - I'm not familiar with this fellow, but a glance at his publication history suggests a type I recognize all too well. I can't help but feel sorry for people who really, seriously have their doubts about the merits of a longer, healthy lifespan. These are people who truly do not enjoy being alive, or worse, people who like life, but are so blinded to the essential nature of opportunity, wealth and the potentials of freedom that they can believe in arguments for the pain, suffering and death of billions in the years ahead. These are folk who can construct an abstract concept, this "society," wholly separate from real individuals, their goals and actions, and somehow justify the most horrific, terrible futures for those individuals. It's like a twisted sort of religion.

If you really don't want to live to 150, then there are plenty of graceful exits along the way. Just don't try to ruin it for those of us who are trying to build a future of real anti-aging medicine and radical life extension, those of us who will revel in what we can achieve and build with more healthy years.

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More TheraVitae Press Attention

(From Reuters AlertNet). One can hope that ever more attention given to successful commercialization of stem cell therapies outside the US will lead to some reduction in stifling regulation within the US. Certainly advocacy groups - such as FasterCures - should be making hay with the success of TheraVitae. "Theravitae is set to begin clinical trials with Thai doctors in January to treat peripheral vascular disease, a circulatory ailment which can lead to amputations. Next up: Parkinson's disease by mid-2006 and some forms of blindness in the first quarter of 2007. Eventually, Theravitae thinks, the technology could be used to treat emphysema, broken bones, renal failure and diabetes. ... Theravitae, which says it will become profitable in January 2006, expects 100 people a month will be coming to Thailand to seek the stem cell treatment by June next year."


An Interview With Leonard Guarente

The MIT Technology Review has an interview with researcher Leonard Guarente, who "has spent much of the last two decades patiently chipping away at the genetic and biochemical underpinnings of the aging process, an area of research often plagued by extreme hyperbole and extravagant claims. ... I hope in 10 years that we are way down the road of drug discovery in finding compounds that will deliver at least some of the benefits of calorie restriction. And I think SIR2 is going to be one of the important targets that we want to go after with drugs. ... We definitely think it is involved in the aging process. In particular, it seems to be involved in sensing caloric intake and asserting effects on cells to adjust life span. We think calorie restriction is a tremendous opportunity for us to intervene pharmacologically and have a positive impact on human health."


From the Camp of Suffering and Death

Leon Kass, advocate for suffering, death and mysticism, a good example of the worst of modern bioethics, is still turning out material in opposition to healthy life extension, it seems. Fortunately, he's no longer heading up the President's Council on Bioethics - although what's left is just as bad, frankly. There Kass is, however, plugging away at the idea that it's a wonderful thing to suffer, decay and die in pain. From the article:

First, medical progress often leads to greater debility in later years even as - and precisely because - it cures deadly diseases at earlier ages. This is the paradox of modern aging: we are vigorous longer and we are incapacitated longer. To be sure, no one wants to turn back the clock to a time when mothers and children died regularly in childbirth, when infectious diseases decimated helpless communities, when heart disease was largely undiagnosed and untreated, and when a diagnosis of cancer meant swift and certain death. But severing medicine's sweetest fruits from its sourest consequences may prove impossible.

Note the sneaking in of a form of the Tithonus error here - it's certainly not true that medical progress leads to greater debility in later life for you and I. In fact, studies show quite the opposite effect.

Second, to see medical progress as a "cost saver" is simplistic at best. Medical care is more expensive than ever precisely because we can do so much more to diagnose and treat disease, and Medicare and Medicaid are costlier because more people are living longer. Even if curing today's diseases becomes less expensive over time, no one knows the cost of dealing with the diseases that will replace them. Only if people live free of illness to the very end and then die suddenly will medical progress really result in cheaper medicine. Otherwise, it will continue to purchase greater longevity and better health at an increased overall expense.

This is nonsense, conflated with socialist nonsense - a classic example of the way in which centralized systems turn opportunities into problems. Being alive has a cost, dependent on circumstance, and technological progress acts to bring that cost down. Being alive means that you can work to create wealth, and thus pay your way and save for the future. For those of us for whom being alive holds a certain attraction, it's all a matter of working towards technological progress, thus bringing the costs of remaining alive down to a manageable level. That living longer costs more should raise no eyebrows. In a free market for healthcare, this would be a state of dynamic growth and optimism - all those people living longer, earning more, spending more, and taking responsibility for their own finances and purchases ... no different than any other aspect of life. For some reason, pundits who romanticise the horrors of aging and the destructive effects of big, centralized government programs just can't see it that way.

None of this implies ingratitude for the blessings of medical progress - including current research aimed at curing age-related diseases like Alzheimer's. But in fueling our love of youthfulness and limitless life, and our hatred of senescence and decline, the campaign for healthy aging also subtly encourages us to devalue the need to give care and comfort to those we cannot cure.

Here we have the projection of unsavory values from a pundit upon the world. From where I stand, healthy life extension advocates are working towards the defeat of age-related degeneration as much for others as themselves. Just take a look at the dedications by MPrize donors, or the In Memoriam donations. The ultimate expression of solidarity for those who will die before real anti-aging medicines arrive is the support given by the healthy life extension community to cryonics organizations.

Kass has a deep and abiding romance with death and aging, a state of mind that apparently blinds him to the very real suffering and very real tragedy of 100,000 lives lost to aging every day. Every day! Why else would he advocate government restrictions on research that could help people lead longer, healthier lives? Kass reaches for whatever arguments he can muster to support his romance; sense and truth fall beside the way. Once you point out the flaws in the three quoted paragraphs above, the entire essay falls apart.

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Kurzweil On Radical Life Extension

The recent 60 Minutes segment on radical life extension was to include an interview with entrepreneur and inventor Ray Kurzweil, but this was not shown in the television version of the broadcast. Fortunately, the KurzweilAI team have found and linked to video of this interview from the CBS website. "When we get to 2030, say, we will have the means to indefinitely extend human life." This builds upon Kurzweil's projected timescales for technological development - in advanced nanomedicine particularly - as put forward in his recent books, Fantastic Voyage and The Singularity is Near. This technology will certainly change the world, and the defeat of aging - by repairing or preventing age-related cellular damage - is just one of the many accomplishments that will become possible.


Towards Molecular Surgery

(From EurekAlert). Scientists are working on ways to break down harmful age-related intracellular aggregates - in this case the amyloid associated with Alzheimer's - using nanoparticles and low-intensity radiation: "Using test tube studies, the scientists attached gold nanoparticles to a group of beta amyloid fibrils, incubated the resulting mixture for several days and then exposed it to weak microwave fields for several hours. ... The fibrils subsequently dissolved and remained dissolved for at least one week after being irradiated, indicating that the treatment was not only effective at breaking up the fibrils but also resulted in a lower tendency of the proteins to re-aggregate, according to the researchers. The same approach also holds promise for treating other neurodegenerative diseases that involve protein aggregation, including Parkinson's and Huntington's."


Progress: If You Want Things Done, Then Get Things Done

Progress is just a matter of getting things done, one step at a time - of slugging away at the problem, leading by example and bringing other folks around to your way of looking at things. Some of them will join in, and then it all becomes interesting. But when it comes down to it, the world moves forward because people take action ... all very prosaic, no mystery at all. Anyone can do it. From FuturePundit:

Those of us who promote the idea of full body rejuvenation as an achievable goal have seen this cause come a long way from the fringe to the mainstream. About 8 or 9 years ago [biomedical gerontologist Aubrey de Grey] was discussing rejuvenation with a small handful of us on the Usenet group Gradually he's made it into major print publications and TV with the idea that aging is curable.

The future is what we make of it, and there's nothing special or reserved in the act of making a difference. All that separates de Grey from most of the rest of us is dedication, determination and persistence - but nothing stops any one of us from taking a single step towards a better future. Those steps will add up. If you don't like the present state of affairs insofar as the future of your health and lifespan is concerned, there's a simple solution: stand up and join those who are doing something about it!

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Myelin Breakdown And Alzheimer's

More on brain aging research from 7news: "The breakdown of myelin, a sheet of fat that insulates nerves and helps speed messages through the brain, appears to be a key contributor to the onset of Alzheimer's disease ... They found the severity and rate of myelin breakdown was correlated with the type of APOE, or apolipoprotein-E, gene a person had. Previous research has shown APOE status to be the second-biggest risk factor for the disease after ageing, with a version called APOE-4 putting persons at highest risk. ... breakdown of myelin, a natural part of the ageing process, proceeded most rapidly for those with APOE-4, less so for those with APOE-3 and most slowly for those with APOE-2. APOE-2 is thought to offer some protection from Alzheimer's, while APOE-3 is seen as neutral. ... These new findings offer, for the first time, compelling genetic evidence that myelin breakdown underlies both the advanced age and the principal genetic risks for Alzheimer disease."


Healthy Life Extension, Taken Seriously

Over at TCS Daily, Glenn Reynolds discusses recent attention given to biomedical gerontologist Aubrey de Grey, the Strategies for Engineered Negligible Senescence (SENS) and Methuselah Foundation: "But what's news isn't so much that de Grey and what he calls "Strategies for Engineered Negligible Senescence" are getting attention. It's that these sorts of ideas are getting serious attention, rather than being dismissed as absurd. The 60 Minutes story does feature scientists who point out that de Grey is invoking technology that hasn't been developed yet, but that's not much of a critique, since de Grey's chief point is that we can develop such technology if we work at it, not that such technologies already exist ... At any rate, the subject, which I've been flogging in these pages for a while, seems to be breaking out. Last year there was a sort of harmonic convergence of academic work on the subject, with three major books published almost simultaneously."


A Dated But Worthwhile Look at Nanomedicine

You'll find the text of the 1991 publication of "Unbounding the Future: the Nanotechnology Revolution" at the Foresight Institute. Dated it may be, but the overview of nanomedicine in chapter 10 is well worth reading - a solid look at what is possible, within the known limits of physics and the knowledge of 15 years ago:

Deadly diseases may be easily dealt with, while minor ills remain incurable, or vice versa. As we will see, a mature nanotechnology-based medicine will be able to deal with almost any physical problem, but the order of difficulty may be surprising. Nature cares nothing for our sense of appropriateness. Horribleness and difficulty just aren't the same thing.


Where does aging fit in the spectrum of difficulty? The deterioration that comes with aging is increasingly recognized as a form of disease, one that weakens the body and makes it susceptible to a host of other diseases. Aging, in this view, is as natural as smallpox and bubonic plague, and more surely fatal. Unlike bubonic plague, however, aging results from internal malfunctions in the molecular machinery of the body, and a medical condition with so many different symptoms could be complex.

Surprisingly, substantial progress is being made with present techniques, without even a rudimentary ability to perform cell surgery in a medical context. Some researchers believe that aging is primarily the result of a fairly small number of regulatory processes, and many of these have already been shown to be alterable. If so, aging may be tackled successfully before even simple cell repair is available. But the human aging process is not well enough understood to enable a confident projection of this; for example, the number of regulatory processes is not yet known. A thorough solution may well require advanced nanotechnology-based medicine, but a thorough solution seems possible. The result would not be immortality, just much longer, healthier lives for those who want them.

Fifteen years later, those involved in the development of advanced nanomedicine - such as medical nanorobots - are much more confident of future capabilities.

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Brain Aging, Common Sense

Randall Parker uses recent research into the genetics of the aging brain as the starting point for some common sense talk on health, aging and the future of anti-aging medicine: "Probably in 20 or 30 years time we will be able to grow replacements for all the internal organs. ... But the brain is our identity and needs to be repaired, not replaced. ... This makes brain rejuvenation much harder than rejuvenation of the rest of the body. We need to slow brain aging because effective rejuvenation therapies for the brain are going to take longer to develop than rejuvenation therapies for the rest of the body. ... Even if you are very confident that a cure for aging will be found before you die that is not a reason to be complacent about your diet and lifestyle. ... Best to delay the onset of assorted maladies as long as you can."


Should We Cure Aging?

(In EGO Magazine). I somehow managed to overlook this rather good Joao Pedro de Magalhaes piece from a few months ago: "The knowledge that every ambition is doomed to frustration at the hands of a skeleton has never prevented the majority of human beings from behaving as though death were no more than an unfounded rumor. ... Aging fosters sickness and disability, increases human suffering, and makes us more likely to die. Yet there are a number of possible objections to the endeavor of curing aging. Most of these are unfounded myths, easy to disprove. This essay draws on my own lectures on the subject and attempts to answer the most commonly raised questions and concerns about a possible cure for aging."


Transcript for 60 Minutes on Radical Life Extension, Aubrey de Grey

I just finished watching biomedical gerontologist Aubrey de Grey's appearance on 60 Minutes, with scientists Jay Olshansky and Christian Sell providing the opposing viewpoints, in a segment entitled "Immortality." How far we've come in the past few years - that the opposing view in a mainstream media publication is now that radical life extension will happen, just not so much and not so fast! Overall, it was one of the most positive mainstream pieces on healthy life extension I've seen; good job all round.

The transcript of the segment can already be found online. A few choice quotes:

"The first generation [of anti-aging therapies] will give us maybe 30 extra years of healthy lifespan," says de Grey. "So, beneficiaries of those first therapies will still be around to benefit from improved therapies that will give them another 30 or 50 years and so on. So this is basically staying one step ahead of the problem." ... "What I'm after is not living to 1,000. I'm after letting people avoid death for as long as they want to," he says.


What I like about Aubrey is, he's not selling anything except ideas. He's set forth a series of testable research hypotheses, which is what science is all about, and he said 'test them'. I love that. That is what we should be doing in the world of science," Olshansky says. "I just wouldn't hold out immortality or 5,000-year life expectancies as the end result or the promise of what you're going to get from this."


"We're talking about saving 100,000 lives a day. And it takes a lot of problems to match that," says de Grey.

De Grey acknowledges that some people will say those 100,000 lives lost a day are just in the nature of things. "But, you know, it didn't stop us from using treatments for infectious diseases when we found out how to develop them," de Grey responds.

People are chained to their blogs nowadays; a nice brace of posts on the 60 Minutes show can already be found with a little hunting:


Being less than a novice when it comes to science - either theoretical or applied - I'm not one to evaluate anyone's biological and genetic claims. It certainly does pique my interest, however, when apparently intelligent and well-qualified scientists make claims about extending life expectancy for several centuries

Superior beardage:

I find all this talk so fascinating. I mean, to live well past 100 seems so out of reach, but then again, at one point man couldn't even conceptualize the technology that would enable us to go into space. Given the speed with which science is expanding (think about the past 10 years even. Look at how much better your PC is now compared to then. Medical treatments: AIDS drugs, cloning, mapping of the human genome, etc.), the possibilities are exciting.

immortality makes me tired:

Maybe someone who expects to live to the ripe old age of 874 will plan out things accordingly, postpone childbirth for a couple hundred years. But if, at 74 and standing on the golf course, I find out I've got almost a thousand more years to shave some strokes off my game, I might not be able to feign excitement.

Fiction may speak truth:

Now, this research is in very preliminary stages. It's not likely that any practical, effective results will be obtained in my lifetime (but neither is it impossible that they might be). It's just fascinating to me that something I read about in a work of science fiction a couple of decades ago might someday actually become reality. Wouldn't that just be the coolest thing?

The Methuselah Foundation volunteers are very pleased, and rightly so. Hopefully this will be first of much positive media attention in 2006.

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Tweaking p53 Without Accelerating Aging

The p53 protein, and the gene producing it, are tied up in the mechanisms linking and driving cancer and aging. p53 makes a very attractive target for cancer therapies, but altering it reduces life span - accelerates aging - in most cases. Here EurekAlert reports on a possible workaround: "Mdm2 is a key inhibitor of p53 and therefore an attractive target to modulate p53 activity in cells. However, conflicting evidence exists regarding whether or not p53-mediated tumor suppression comes at the cost of accelerated aging. ... The possibility that inhibitors of Mdm2 could delay cancer in such people without causing detrimental side effects is bolstered by our demonstration that mice expressing 30-80% the normal level of Mdm2 develop fewer tumors than wild type mice, yet age normally."


New Methuselah Foundation Website

There's nothing quite like imminent television publicity to push forward needed updates: as I'm sure some of you have noticed, the Methuselah Foundation now has its own website, separate from the website for the MPrize for anti-aging research that has been the main foundation focus for the past two years. The new site gives equal billing to the nascent Institute for Biomedical Gerontology, Aubrey de Grey's organization, long on the drawing board, that has now started forward with LysoSENS research. The Institute will be going much further towards funding meaningful anti-aging science based on the Strategies for Engineered Negligible Senescence (SENS) in the future, we all hope.


Seemingly Endless Failure

A few of the seemingly endless failures of centralized, regulated health systems are illustrated in this News-Press piece. In a free market, needs - and the accompanying price signals - become opportunities for entrepreneurs to fund development and people to provide the needed services. In a centralized, regulated system, needs are problems; the price signals and profit motives are not there, so shortages, rationing and poor quality service result. Only socialized medicine can turn the wonderful lengthening of human life span into a massive problem and squash the prospects for future longevity research at the same time. As one libertarian writer pointed out, "If telomerase inhibitors were a new kind of computer chip, they would have been on every Wal-Mart pharmacy shelf and selling for ten dollars a bottle by now."