Alzheimer's as a Form of Diabetes
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A rather fascinating entry on Alzheimer's research can be found in various media outlets today.

Researchers at Rhode Island Hospital and Brown Medical School have discovered that insulin and its receptors drop significantly in the brain during the early stages of Alzheimer's disease, and that levels decline progressively as the disease becomes more severe, leading to further evidence that Alzheimer's is a new type of diabetes. They also found that acetylcholine deficiency, a hallmark of the disease, is linked directly to the loss of insulin and insulin-like growth factor function in the brain.

"Insulin disappears early and dramatically in Alzheimer's disease. And many of the unexplained features of Alzheimer's, such as cell death and tangles in the brain, appear to be linked to abnormalities in insulin signaling. This demonstrates that the disease is most likely a neuroendocrine disorder, or another type of diabetes,"

...

We're able to show that insulin impairment happens early in the disease. We're able to show it's linked to major neurotransmitters responsible for cognition. We're able to show it's linked to poor energy metabolism, and it's linked to abnormalities that contribute to the tangles characteristic of advanced Alzheimer's disease. This work ties several concepts together, and demonstrates that Alzheimer's disease is quite possibly a Type 3 diabetes," de la Monte says.

Earlier this year, de la Monte and co-authors provided the first evidence that insulin and its related proteins are produced in the brain and that reduced levels of both are linked to the late stages of Alzheimer's. They surmised that Alzheimer's is a complex neuroendocrine disease that originates in the central nervous system, raising the possibility of a new type of diabetes.

So, is this cause or effect? Or both, in a mixed and more complex package of biochemical mechanisms? Sadly, I am not even remotely qualified to discuss whether or not this is an important breakthrough on the path to preventing and curing Alzheimer's. But in general, I think we can all agree that getting a better handle on the biochemical roots of Alzheimer's would be a good thing. It won't be too many years now before organs can be regrown and replaced in worst case medical scenarios ... but that isn't an option for the brain. If you're in the first half of your life today, it's progress towards preventions and cures for neurodegenerative conditions that should be occupying your long-term view.

Keep an eye on this branch of research; if verified, it may just confirm the best known ways to avoid or delay onset of Alzheimer's within the next few years. Even that is a big deal in this era of racing biotechnology and medical research - a decade of healthy delay will make a big difference in terms of quality and capability of healthcare you'll receive when you need it.

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Nerve Regeneration From Nose Cells?
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From the Guardian, a look at a research group that is attempting to use cells from the nose to regenerate presently untreatable nerve damage: "Studies in animals have established that the cell implants can restore nerve functions. Rats with severed nerves have regained functions of a forepaw. But the first human study, which tests the safety of the procedure, will be limited to patients with one very specific and similar injury to ensure the results are clear. ... If successful, with refinement and research the procedure could be tried on people in a wheelchair. It also has the potential to heal other nerve injuries, such as those caused by stroke, blindness and deafness."

Link: http://www.guardian.co.uk/medicine/story/0,11381,1653838,00.html

Update On CIRM, Lawsuits
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(From SFGate). The lawsuits holding up the issuance of public funding for stem cell research from the California Institute for Regenerative Medicine appear to be on the way out: "California's embattled Proposition 71 stem cell program took a big step Tuesday toward overcoming lawsuits that have blocked its first grants from being issued. Alameda County Superior Court Judge Bonnie Sabraw denied essentially every legal argument brought by the plaintiffs in litigation alleging that Prop. 71 violated the state Constitution because it would allow taxpayer-backed bond revenues to be distributed without direct legislative control." The legal grounds of these lawsuits have nothing to do with the reason they were brought - ideological opposition to embryonic stem cell research, regardless of the benefits it will bring. Which is not to say that I agree with public funding initiatives and all the trouble that invariably comes with them.

Link: http://sfgate.com/cgi-bin/article.cgi?f=/c/a/2005/11/30/STEMCELLS.TMP

Bad Points on a Good Foundation
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The Technology Review is reprinting the satirical exchange between Richard Miller and Aubrey de Grey on the topic of the Strategies for Engineered Negligible Senescence approach to the future of medicine. Please do feel free to add your comments to those already there at the foot of the article.

That wasn't what caught my eye, however. It was this post on the part of David Rotman. It really is a poor piece of work despite the basic truth of the premise: there is a great deal of similarity between the debates within gerontology over the future development of anti-aging medicine and those within the nanotechnology research community over the future of molecular manufacturing. The backdrop is similar too: marketeers pushing nanopants on one side, and life extension pills or worse on the other.

The old guard of researchers in both cases are, for whatever reason, reluctant to embrace change and rapid progress, overly skeptical of approaches that may bring results more quickly. That said, it would take a mindset particularly resistant to reality at this point to think that Richard Smalley was leading a heroic charge against "nano fantasists." He was calling them as he saw them, and all of his relevant points have been disproven or debunked; end of story. Smalley's "higher" goals - such as attacking true visionaries like Drexler, or trying to deflate what he saw as hype that would damage funding prospects - were neither noble nor worthy. I posted briefly on this whole sordid nanotechnology industry episode back when it threatened to spill over into the trashing of advanced nanomedicine as a worthy line of research.

Sadly, I can see much of the same all-too-human action at work in the debate within and around gerontology over engineered longevity. So let us just set this down here in stone: the scientific basis for the future of molecular manufacturing and advanced nanotechnology - both in and out of medicine - is very sound. So is the scientific basis for the future of working anti-aging medicine. Getting from here to there is a "just" a matter of a great deal of funding and hard work. Arguing against the fruition of either field of science is simply not a job with long-term prospects.

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Profile Of A Tissue Engineer
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A look at one of the faces behind tissue engineering research is in the New York Times: "We are the people interested in building living systems in humans and animals called the tissue. We start with the basic building blocks of these systems, which are cells or different proteins or molecules, and then we reassemble them into something that becomes living tissues within a body. The promises of tissue engineering are many. In trying to regenerate cartilage, we're very far along. In terms of progress, things related to our cartilage, bones, skin, we're likely to see products within 5 to 10 years. The really big impact areas - treatments for Parkinson's disease and diabetes - those will happen later, within my lifetime."

Link: http://www.nytimes.com/2005/11/29/science/29conv.html?pagewanted=print

Same Old, Same Old
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(From Salon). It takes a certain type of doublethink to write a mainstream article on the future of nanomedicine, it seems. How else to explain a piece that lists the tremendous benefits to come, and then tries to convince us - with an array of hoary old straw men and disproved arguments - how terrible it will be to live in such a world? "It's the not-too-distant future, say 2016. You have been diagnosed with Stage III melanoma. Cancer has metastasized throughout your body. Just ten years ago, in 2006, the choice of treatment would have been based on the type of primary cancer, the size and location of the metastasis, your age, general health, and your treatment history. Your prognosis would have been gloomy. But that was back in 2006, before we entered the era of nanomedicine."

Link: http://www.salon.com/tech/feature/2005/11/28/nanomedicine/index_np.html

Stem Cell Commercialization Spreading
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From Today Online, an indication that the commercialization of stem cell therapies is spreading - outside the US, in any case: "With its doctors at the vanguard of pioneering stem cell therapy, South Korea is looking to become a 'medical tourism' destination for foreigners unable to find cures in the own countries. Two foreigners have already received therapy at South Korean medical firm Histostem, which has perfected a method of stem cell therapy using umbilical cord blood and boasts the biggest stock of cord blood and stem cells in the world." This is good news for anyone seeking to benefit from early regenerative medicine within the next ten years - it looks like things are beginning to take off.

Link: http://www.todayonline.com/articles/86877.asp

More Video From the Immortality Institute Conference
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Randy Wicker has posted two more short videos from the recent Immortality Institute conference; links are below.

Talking to biomedical gerontologist Aubrey de Grey:

In this interview, Aubrey de Grey Ph.D. discusses how he became the major spokesman for human immortality. He also muses on the impact his beard has on his crecdibility.

Researcher Michael Rose presents:

After a few comments by Aubrey de Grey Ph.D., a professor from Cambridge University who has become the world's most notable champion of extending human longevity through science, Michael R. Rose Ph.D., a Professor in the Department of Ecology and Evolutionary Biology at the School of Biological Sciences, University of California, Irvine, explains how studies of the aging mechanisms in fruit flies and mice promise to enable human beings to greatly extend their lifetimes.

You'll find more on the same subject - and more video - in a post earlier this month.

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Gene Therapy Versus Atherosclerosis
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Via ScienceDaily, news of another promising gene therapy in the works: "Cardiology researchers at Cedars-Sinai Medical Center have found that a single injection of a harmless virus engineered to carry a beneficial, mutant gene enabled animals to manufacture their own supply of the gene's protein product that protects against plaque buildup in blood vessels. As a result, the amount of plaque was significantly reduced, as was an immune reaction that can lead to plaque buildup and rupture, which can cause a blocked artery and heart attack or stroke. ... a clinical trial was conducted in humans with similar results. After five weeks of once-a-week injections, [the protein produced by the gene] significantly shrank plaque in coronary arteries. The protein appeared to actually remove bad cholesterol, even from sites on arteries where plaque had accumulated."

Link: http://www.sciencedaily.com/releases/2005/11/051126140633.htm

Stem Cell Therapy In China
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The Kansas City Star takes a look at the work of Huang Hongyun, representative of a number of groups worldwide performing varied stem cell therapies in a professional manner, but without the rigors and tests of scientific trials. "Right now, besides ALS and spinal injury, we do brain damage, MS. Also, we treated another patient whose genetic disease caused vision damage. He lost his vision. Not totally. He only can see very, very little. After several weeks, he got some, not very much, but got better. ... So far, he hasn't produced controlled studies that compare the progress of patients who receive the therapy to those who don't. And critics say much of his evidence of patient improvement is based on anecdotes, rather than on hard scientific measurements." Caveat emptor.

Link: http://www.kansascity.com/mld/kansascity/13264821.htm

Longevity Genes, Ashkenazi Jews
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You may be passingly familiar with the work of Nir Barzilai in studying centenarians in the Ashkenazi Jewish population for genetic similarities that may explain their longevity:

Dr. Nir Barzilai, who has been studying centenarians for genetic and biochemical clues to longevity. At the top of the list so far: HDL and lipoprotein size ... Small lipoproteins imply a shorter, less healthy life.

Armed with genes, modern biotechnology makes it the work of less than a year to completely understand the mechanisms involved - the trick is to determine which genes are important. Work on human biochemistry is the biggest and most important reverse engineering project of our time.

The website for Barzilai's project makes for an interesting read if you'd like to learn more about how this and other centenarian and longevity studies actually operate.

Up to the 17th century, the Ashkenazi Jews in the Pale of Europe encountered a combination of plagues, wars and anti-Semitic persecution, contracting the population to an estimated few hundred thousand. Combined with a long history of isolation and virtually no intermarriage, the Ashkenazi population today is derived from a relatively limited number of founders. The gene pool of Ashkenazi Jews, therefore, is unique and more homogeneous than most other populations. It is easier to spot genetic differences in this group, precisely because there is so much similarity in the genetic makeup.

Although participants in this study must be Ashkenazi Jews, the findings will be relevant to everyone, regardless of their ethnic or religious background.

...

Results of our research to-date have been encouraging and enthusiastically received by the medical research community. ... While there is still much more work to do, we are confident that we are on track to unraveling the mystery of extreme longevity, and finding the keys to a long, healthy life.

This sort of research is a branch of the larger tree of metabolic and longevity research. Over on the other side, you'll find calorie restriction studies - attempts to understand how calorie intake and metabolic regulation mechanisms determine the rate at which age-related damage accumulates, and thus determines healthy life span. We can hope that this field illuminates much that we'll need to know in order to greatly extend the healthy human life span - once scientists develop sufficient control over our biochemistry, that is. I'm not sold on metabolic tinkering as the best path forward to radical life extension, however. We need to do better than simply slow aging - we need to get in there and repair or prevent age-related damage ... which may actually turn out to be the faster, more effective way forward.

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Tomorrow's People
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A potentially interesting conference - with a live stream to the Internet promised - will be hosted by Oxford University's James Martin Institute in March 2006, entitled "Tomorrow's People: The Challenges of Technologies for Life Extension and Enhancement." It has the sound of an affair with modern luddite leanings (i.e. the hard work and uncertainty of progress is all but dismissed in favor of discussions of ethics, control, slowing things down, poorly assessed "risks," and the "need" for governance), but many of the speakers and panellists are scientists first and foremost, and a number were at the Second Strategies for Engineered Negligible Senescence conference. One would hope that these sensible folk can keep the bioethicists from turning the conference into an exhibition of bad bioethical behavior.

Link: http://www.martininstitute.ox.ac.uk/JMI/Forum2006/

A Worm Is At Work
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From the website of Gregory Benford and Michael Rose, behold the missing chapter from The Long Tomorrow, subtitled "An Insider's View of The Genetics of Aging, circa 2004." It makes for an interesting read: "The future, it seems to me, lies with research that attempts to give to us the beneficent life of the evolved Methuselah flies. They live even longer when they are calorically deprived, but such deprivation is not necessary to their postponed aging. If we could eat our normal diets, keep our normal activity levels, take care of our children, AND do all of these things for longer, then we would have true amelioration of aging. The creations of the gene jockeys and the diet manipulators can be admired for their brilliance, their scientific acuity. But they aren't supplying a future for humankind that most of us are likely to want." You may recall that Rose thinks calorie restriction will not significantly prolong human life in any case.

Link: http://www.benford-rose.com/wormisatwork.php

Benford and Rose Essays
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Gregory Benford and Michael Rose, both scientist-authors with an interest in healthy life extension and related topics, publish essays on their collaborative website that are sold for a few quarters apiece via Amazon Shorts. Depending on how you feel about micropayments and buying access to documents online, it may be worthwhile to put down a dollar for the following:

The New Methuselahs:

We may now begin to pry humanity loose from the vise of aging. What are the realistic prospects for postponing aging, if not obliterating it? Some recent biotech promises to understand and impede aging, and we can accelerate this work. But some find this undesirable, if not immoral. We review the debate from a variety of angles: scientific, ethical, and literary. There is real hope.

Back From the Freezer?:

Cryonics companies suspend their dead "patients" in liquid nitrogen. Bringing them back is not obviously impossible, but research to make it happen will probably take half a century or more. This is a long shot chance to see the future, utterly American. Scientific issues might be overcome, but social impediments are large, too. At least cryonics makes it possible for you to die with some hope, however small.

As an added bonus, you'll also find the "lost" chapter from The Long Tomorrow.

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Patient-Specific Stem Cell Lines
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Embryonic stem cell lines are essential for much of the most important stem cell research, and as Medical News Today points out, "producing individual patient cell lines for our own future needs is now something we might all want to consider. ... a method for replacing the nuclei of [embryonic stem cells (hES)] by somatic cell nuclei has been widely sought. ... The new technique involves the fusion of different types of somatic cells with hES cells. The resulting 'cybrids' were shown to have the genotype of the donor somatic cells and the 'stemness' (the ability of the cells to divide, change throughout our lifetime, to provide cells that can become specialised and to replace those that die or are lost) of the recipient hES cells." This is very promising for the near future of regenerative medicine if verified by the wider scientific community.


Link: http://www.medicalnewstoday.com/medicalnews.php?newsid=34176

Support Alcor's Vitrification Research
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Cryonics is a scientific approach to developing a chance to avoid death for those of us who will not live long enough to see working anti-aging medicine, nor participate in the process of actuarial escape velocity. The non-profit Alcor Life Extension Foundation is the largest provider of cryonic suspension services; amongst other activities, the Alcor staff, volunteers and associates are engaged in improving the process of vitrification, an alternative to freezing that avoids tissue damage issues:

Vitrification is an ice-free process in which more than 60% of the water inside cells is replaced with protective chemicals. This completely prevents freezing during deep cooling. Instead of freezing, molecules just move slower and slower until all chemistry stops at the glass transition temperature (approximately -124°C). Unlike freezing, there is no ice formation or ice damage in vitrified tissue. Blood vessels have been reversibly vitrified, and whole kidneys have been recovered and successfully transplanted after cooling to -45°C while protected with vitrification chemicals.

From the latest Alcor newsletter, we learn that a $100,000 matching grant applies to all donations to whole-body vitrification research and developement until January 31, 2006.

A better cryopreservation can be yours. That's why our staff, including senior research scientist Sergey Sheleg, MD, PhD, is actively working to cryopreserve your intact body and brain as perfectly as possible.

Progress is already underway. Alcor recently upgraded its whole body cryopreservation procedure by switching to M22, an advanced cryoprotectant capable of vitrifying the brain for whole-body members, but parts of the body are still not fully vitrified. We need your help to reach the next level.

We need the help of every one of our members now to achieve whole-body vitrification. Until January 31, 2006, every dollar donated will be matched up to $100,000 by a generous donation from Bina & Martine Rothblatt, Alcor members dedicated to rapidly advancing this technology.

Call now to make your pledge: 877-462-5267 ext. 101

Or print and fax your pledge form to: 480-922-9027

[PDF format] Pledge forms are available at this link: http://www.alcor.org/Library/pdfs/MatchingGrant.pdf

When sending donations by mail, include this pledge form or simply write "Matching Grant Donation" in the memo field of your check:

Alcor Foundation
7895 E. Acoma Drive, Suite 110
Scottsdale, AZ 85260
Attention: Fundraising Dept.

If you have been considering a donation to one of the non-profit cryonics organizations, this would be a good time.

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Scientists' Open Letter on Cryonics
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The Scientists' Open Letter on Cryonics includes signatories of the calibre of Eric Drexler, Robert Freitas, Marvin Minsky and Gregory Stock, to pick just a few. "Cryonics is a legitimate science-based endeavor that seeks to preserve human beings, especially the human brain, by the best technology available. Future technologies for resuscitation can be envisioned that involve molecular repair by nanomedicine, highly advanced computation, detailed control of cell growth, and tissue regeneration. With a view toward these developments, there is a credible possibility that cryonics performed under the best conditions achievable today can preserve sufficient neurological information to permit eventual restoration of a person to full health. The rights of people who choose cryonics are important, and should be respected."

Link: http://www.cryoletter.org/

Aging And The Cell Nucleus
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From PLos Biology, a very accessible look at what we know about aging and accelerated aging conditions in terms of change in the cell nucleus. "The cell nucleus in higher organisms is now recognized as a complex, highly organized repository of an individual's genetic information. ... The first hint to a surprising connection between nuclear architecture and aging came from yeast, when Leonard Guarente and colleagues found that a protein, Sir4, whose mutation results in extension of life span, localizes to the nucleolus, one of the most prominent subcompartments of the cell nucleus. The link between aging and nuclear organization was further strengthened by the observation that the localization of the protein and the morphology of the nucleolus itself changed as yeast cells aged."

Link: http://biology.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pbio.0030395

Send Soil Samples to Help LysoSENS Research
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John Schloendorn is advancing LysoSENS research - a branch of the Strategies for Engineered Negligible Senescence, a meaningful approach to developing working anti-aging therapies - by running screening experiments for soil microbes capable of breaking down harmful aggregates and metabolic byproducts in and around human cells. Schloendorn would like to get the wider healthy life extension community involved, and he explains how you and I can help his work in a post at the Immortality Institute forums:

As most of you know, Lyso-SENS is a recent effort by the Methuselah Foundation to target age-related storage diseases, which are caused by the accumulation of some pathogenic chemical substance in the body with age. Examples of age-related storage diseases are Alzheimer's disease (amyloid and tau aggregates), heart disease and stroke (cholesterol and oxidized cholesterol species in the artery wall), age-related macular degeneration (lipofuscin of the retinal pigment epithelium) and skin wrinkles (advanced glycation end products of the extracellular matrix). As such, Lyso-SENS targets three of the seven SENS pillars: Intracellular aggregates, extracellular aggregates and extracellular crosslinks.

Lyso-SENS works by using methods from environmental bioremediation to find soil microbes capable of degrading the target substance. We then hope to isolate the enzymes used by these microbes to do so and use them for therapy in a way that is similar to current enzyme replacement treatments for congenital lysosomal storage diseases. However, not all soil microbes are amenable to our screening methods, not all enzymes we may discover will work in the human physiological environment, some will have deleterious side-effects, and so on. So we need many sources of different microorganisms to begin with.

This is where you come in. Please send us soil samples from your area, from places that you think are likely to contain microbes capable of degrading age-related aggregates. About a handfull of soil (100-200 grams) will be plenty. The more microbial diversity we can put into these experiments, the better will be our chances of sustained success. So your participation will truly increase the chances of success of the Lyso-SENS project.

Please read the whole piece for details regarding which samples and locations are likely to be useful, how to package the samples and where to ship them. If you have questions or suggestions, you can post them in that discussion thread.

Do your part to help! Remember that you can also donate money to help fund LysoSENS research at the Methuselah Foundation website.

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Searching For The Roots Of Regeneration
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If we understood the genes and mechanisms that control regeneration and healing, there is every likelihood we could make the process work in new and better ways - or stop failing as we age. With that in mind, EurekAlert covers research into the genetics of regeneration in planarian worms: "when a gene called smedwi-2 is silenced in the adult stem cells of planarians, the quarter-inch long worm is unable to carry out a biological process that has mystified scientists for centuries: regeneration. ... The smedwi-2 molecule is doing something early in the specification of stem cell progeny that modulates their ability to differentiate into the proper cell type ... How this molecule is modulating stem cells is one of the next steps that he and Reddien are trying to solve. The answer could have far-reaching implications, because genes similar to smedwi-2 are found in plants, animals and human beings."

Link: http://www.eurekalert.org/pub_releases/2005-11/uouh-sgi112305.php

Stem Cell Research: A Look Back
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I'm a sucker for a certain type of popular science book, pulling back the curtain to watch the scientific method in progress. InformIT is excepting from a new book on the recent history of stem cell research: "The scientific and medical implications contained in this short paper are profound and unambiguous. Embryonic stem cells could be used to generate new tissue and organs for transplantations. Defective and dying tissues caused by diseases such as Parkinson's or diabetes could be replaced with an unlimited supply of specially grown stem cells. Cultures of human stem cells could be used as laboratory tools to help identify new drugs and therapies. For pure scientists like Thomson, observing stem cells in the laboratory could provide insights into how all animals embark upon the magnificent developmental process that begins with a single cell."

Link: http://www.informit.com/articles/printerfriendly.asp?p=424446

The Iniquity of Enforced Retirement
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Retirement forced on people who are perfectly capable and willing to work is a terrible thing. Only in a dreadfully twisted social environment can more willing workers be transformed from boon into problem. Sadly, most of us live in just such a society, repleat with forced wealth transfers, counterproductive medical regulations, and the tragedy of the commons writ large upon taxed wealth and shoddy government monopoly services. This is what happens when socialist ideas prosper.

Fortunately, most people want none of it - at least when it comes to goverment employees forcing them out of their jobs:

Many over-55s are set on working until they are in their 70s, according to the HSBC research.

"Longevity is driving revolutionary change in the way that older people think about their later years and, for most, this new chapter in life includes periods of work," comments Steve Troop of the bank.

He says that it is "crucial" that governments and companies across the world adapt their systems so that people will be able to continue working for as long as they want to.

A fixed retirement age is not an idea that appeals to many older people. Of those polled, only 16 per cent supported the idea.

Sadly, those same people who are up in arms when their fortunes wane are happy to outrightly or tacitly support the worst of policies that seem to grant them entitlements. There are always hidden costs - and the hidden cost of any form of socialism is slower progress, higher costs, and worse products. When the field in question is medicine, this will potentially cost you your life and health ... or at least a goodly portion of it.

What drives progress and the creation of wealth? Freedom, property rights, and the rule of law. Diminish any of these, and the prospects for the future become dim.

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More On p53
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Medical News Today has a better article on the recent study of the p53 gene and longevity in fruit flies: "When the p53 gene is damaged or missing, cancer may result. In fact, more than 50 percent of human cancers carry p53 mutations. ... When p53 is hyperactive - pumping out higher-than-normal levels of tumor-suppressing protein - it accelerates aging and shortens life span in mice. ... What this new work shows is that there is a 'golden mean' with p53. By targeting a decrease in p53 protein, specifically in neurons, we can extend healthy life span in fruit flies. ... We believe that p53 is part of the caloric restriction life span extension pathway. It's not the entire explanation, but it appears to play a major role." The calorie restriction connection is fascinating, given recent news. It appears that much of interest in biochemistry touches on calorie intake in some way.

Link: http://www.medicalnewstoday.com/medicalnews.php?newsid=33964

Better Biomimicry
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(From Voice of America). If we can build artificial prosthetic arms, why not artificial, prosthetic skin or even blood vessels? The technology of artificial replacements blends into tissue engineering at its cutting edge, where work progresses on a competing set of methodologies to replace or repair damaged tissues and organs. "With a $6 million dollar grant from the U.S. Army, the Portland laboratory is studying elastin and other substances as tools for army medics on the battlefield. One of the products they developed is a patch made from chitosan, which is a fiber extracted from the shells of crustaceans, like shrimp and crabs. The bandage stops serious bleeding by fusing itself directly to a wound ... Dr. Gregory and his team hope to develop elastin tissue for all kinds of replacements: skin, stomachs, intestines, arteries and eventually entire body parts."

Link: http://www.voanews.com/english/2005-11-23-voa68.cfm

Talking About Human Growth Hormone
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It's actually somewhat costly to talk about human growth hormone when you're an online venture. Mentioning it here will no doubt cost me time and bother in future mailings of the Longevity Meme newsletters; everyone suffers when the self-proclaimed "anti-aging" marketplace outdoes itself in the promotion and branding of an aspect of medicine or biotechnology. It becomes next to impossible to find reputable information or sensible, informed discussion of the subject, and soon enough all talk of the matter finds its way into spam filters thanks to shady online mass marketing.

Here's an article that is at least moderately well informed:

The synthetic hormone may not be all that effective for adults, either. It's true that the body's natural growth hormone plays an important role, promoting tissue repair, strengthening bones, and stimulating the immune system. Those who tout its powers point out that levels of growth hormone in the body decline with age, and they claim that replacing the hormone with the synthetic version will slow the aging process. But Olshansky says few studies support that claim, and some seem to counter it. In a 2003 study, mice with superhigh levels of growth hormone had significantly shorter lifespans than normal mice.

Growth hormone, once you cut through the irresponsible marketing, is nothing more than another fairly outmoded workhorse therapy for very specific conditions. The anti-aging marketplace could just as easily have worked itself up into a frothing mania over an osteoporosis drug, or something to mitigate menopausal symptoms - the brand snowballs in size and the money treads science underfoot for these people. But we get along just fine and well in our use of other marketplaces with equally outrageous and disreputable margins, such as the automotive repair or parts industries. As I point out at the Longevity Meme:

You'll hear much light and noise from all sides, so let's just cut to the chase: people should be free to do whatever they like to their own bodies, provided they take responsibility for the consequences. Growth hormone therapies appear to be helpful for some people under some circumstances, but the level of scientific backing for general use that I'd be comfortable with is not there (unlike for, say, calorie restriction). Like many present day therapies, in this era prior to widely available personalized medicine, it's pulling the big red lever and hoping for the best. Results and side effects vary widely, and there are many voices out there making money from hyped, false claims. But none of that is grounds for governmental restriction of choice.

Caveat emptor and educating yourself when the decision matters is a much better philosophy than relying on disinterested and unmotivated regulators to watch out for you.

You'll find an ongoing discussion of growth hormone in the Immortality Institute forums if you'd like to investigate the issue further.

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A History of Cancer Vaccines
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Since we seem to be focused on cancer for the moment, here is an examination of the history of slow progress towards cancer vaccines from the LEF News: "Twenty years ago, when people announced immunology would conquer cancer, people didn't realize how little they knew about the immunology of cancer ... For 20 years, scientists have dreamed of creating vaccines that teach the body to destroy tumors. Yet after hundreds of clinical trials, not a single vaccine has been approved to treat cancer. Yet everybody is still trying. There are at least six cancer vaccine trials planned or under way in South Florida, and more than 100 other trials around the country. Their goal is not to prevent cancer, but to treat it -- to stimulate the body to attack cancers of the skin, prostate, pancreas, breast and lungs, to name a few."

Link: http://www.lef.org/news/LefDailyNews.htm?NewsID=2987&Section=DISEASE

More Evidence For Cancer Stem Cells
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Via EurekAlert, more evidence for cancers being caused by errant stem cells: "Researchers elsewhere already have implicated stem cells in the development of leukemia, and Steindler's lab previously discovered stem-like cells in brain cancer. Others have identified these same cells in some breast cancers. ... The cancer stem cell theory holds that a small subpopulation of rogue stem cells exists within a tumor and has the ability to sustain itself. As these abnormal cells divide, they may generate the bulk of a malignant tumor, then help to spur on its growth. ... The next step, which is ongoing, is isolating and growing tumors from these cells in animals and then finding ways to interfere with that growth based on their stem cell biology."

Link: http://www.eurekalert.org/pub_releases/2005-11/uof-uss112205.php

Groundwork for Human Immune System v2.0
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Recent research into the immune system demonstrates that, armed with the rapidly improving tools of modern biotechnology, scientists are progressing nicely towards a working understanding of crucial systems within the human body. "Working understanding" here means sufficently detailed knowledge of the biochemistry to be able to replicate or steer these processes in cells, and then later - armed with advanced medical nanotechnology - to replace component parts altogether.

Every T cell wears a unique molecule, called a T cell antigen receptor, on its surface that it uses to detect pieces of foreign proteins called antigens. These receptors exist in astonishing, and for all practical purposes, unlimited variety--allowing the body to recognize any pathogen it might encounter.

Just as police need evidence of a crime to begin an investigation, T cells must recognize a specific antigen before they start to fight an infection. Dendritic cells constantly scour the body for antigens and present these to T cells for review in the lymph nodes. It is a demanding job. "Just 10 dendritic cells can show viral antigens to over a million T cells in a day," says Dr. Dustin.

Once a T cell's antigen receptor finds an antigen match, the T cell forms an immunological synapse with a dendritic cell through which it queries the dendritic cell for additional information about the antigen and its source in the body. Is the antigen a danger or simply a harmless food protein? The interrogation may last hours, and if the antigen is deemed a threat the T cell starts multiplying, eventually producing thousands of copies of itself. These T cell clones are capable of killing invaders outright and marshaling other cells to destroy them.

In the new study, Gabriele Campi, a graduate student in Dr. Dustin's laboratory, and Kaspar Mossman, a graduate student of Dr. Groves's, created a synthetic dendritic cell using purified antigen and adhesion molecules (molecules that the cell can grip) in a thin fluid coating on a glass surface. In prior studies the antigen was free to move over the entire glass surface, but in this study they set up miniscule chrome barriers, allowing them to modify the pattern of T-cell antigen receptor clusters in the immunological synapse.

...

"This is the first time that anyone has been able to physically manipulate the immunological synapse and measure the effect on T cell signaling."

This is an early step in the early groundwork for the development of artifical - and far more effective, long-lasting and efficient - immune system components. In all of science, viewing preceeds understanding, which preceeds manipulation and construction. As the tools of nanoscale engineering and then molecular manufacturing become more capable in decades ahead, tremendous opportunities for healthy life extension through engineering and nanomedicine will be there for the taking.

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p53, Cancer and Aging
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Cancer and aspects of cell aging share many of the same biochemical mechanisms and components; the present structure and life cycle of cells is probably an evolutionary balance between protection from cancer and avoidance of other life-shortening conditions. From EurekAlert: "The p53 protein is known to be a critical player in our body's natural defense against cancer ... Although researchers over recent years have established a foothold in understanding how p53 protects against cancer, the mechanisms by which it might contribute to aging and lifespan are not well studied. In work reported this week, researchers studying p53 function in fruit flies show new evidence that despite the protective role of p53 as a guardian against tumor formation, normal levels of p53 activity - at least in some cell types - may indeed contribute to aging and decreased lifespan."

Link: http://www.eurekalert.org/pub_releases/2005-11/cp-nct111805.php

A Cell Is A Cell Is A Cell
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The myriad classifications for human cells, all running on the same basic biochemical and genetic toolkit, are really an indication of our ignorance of the details of that toolkit and it's complexities. As our knowledge grows, we start to see fascinating experiments like this one, detailed at Medical News Today: "the microenvironments of two human embryonic stem cell (hESC) lines (federally approved) induced metastatic melanoma cells to revert to a normal, skin cell-like type with the ability to form colonies similar to hESCs. The researchers also showed that these melanoma cells were less invasive following culture on the microenvironments of hESCs." Cellular machinery responds to triggers, and we know all too few of them. Exploration of this sort helps move us towards a world in which cancer can simply and easily be turned off.

Link: http://www.medicalnewstoday.com/medicalnews.php?newsid=33885

More On Those Ten Longevity Genes
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Medical News Today has a better piece on the ten new longevity-related genes discoved in yeast: "the researchers tested two - Tor1 and Sch9 - to confirm their connection to caloric restriction. One test combined caloric restriction with the genetic mutation to Tor1 that reduced signaling on the TOR pathway. They saw lifespan increases in the resulting yeast cells that were about the same as a cell that had just the Tor1 mutation, indicating that the mutation was doing the same thing as caloric restriction. The TOR pathway is evolutionarily conserved, meaning it is common to many lifeforms. We'd like to know if this is the pathway through which caloric restriction affects lifespan. We think this may be why mice live longer with calorie restriction, because of TOR pathway down-regulation."

Link: http://www.medicalnewstoday.com/medicalnews.php?newsid=33884

Where to Find Out More About Calorie Restriction
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With all this discussion of the biochemistry and genetics underlying the increased healthy longevity granted by calorie restriction (CR) to almost all species studied to date, you might be wondering where to find out more about the practice of CR as a practical matter for humans. Fortunately, there is an introduction to calorie restriction as a diet and lifestyle choice at the Longevity Meme:

What is CR? In short, a CR diet aims at reducing your intake of calories to 20-40% less than is typical, while still obtaining all the necessary nutrients and vitamins. ... Calorie restriction ("CR" from here on in) is the only diet that has been proven to extend healthy life span in mammals such as mice and primates. Some studies have shown up to a 40% increase in healthy life span over non-CR test subjects. CR also provides numerous secondary health benefits, such as a far lower risk for most of the degenerative conditions of aging. From what scientists know of the way in which calorie restriction works, and from the results of recent studies like CALERIE, many are confident that it will produce the same secondary healthy benefits in humans. The degree to which CR can extend the maximum healthy human life span is open to debate, but the evidence for at least some healthy life extension is compelling.

Other good short introductions and overviews online include the follow:

These guides and overviews will point you to some of the better books on the subject, such as "Beyond the 120 Year Diet" by the late Roy Walford, or the recent "The Longevity Diet." I wouldn't recommend starting CR without having read at least one of these - calorie restriction is very simple in concept, but managing the practical details and finding a routine you are comfortable with can be a challenge. It's a great deal easier with a map in hand, so to speak.

With this in mind, it's also very helpful to keep up with the various CR bloggers; a selection follows:

Last, but far from least, you should certainly join the Calorie Restriction Society email lists - which are high volume at times, so you might want to consider the digest versions. The society and its yearly conventions are the center of a friendly and supportive community of CR practitioners of all stripes; a good place to take your questions and comments.

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Watching VesCell, TheraVitae
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As you may recall if you read Fight Aging!, TheraVitae is attempting to commercialize offshore stem cell treatments for US residents; the degree to which they succeed will certainly be widely noted in the venture investment community. This release at Genetic Engineering News gives some indications as to how the effort is going: TheraVitae has "presented interim clinical data showing significant improvement in patients suffering from severe angina pectoris six months after they received the company's autologous adult stem cell therapy. ... The benefit to patients' quality of life is a particularly positive aspect of the results we have seen and has convinced us to start treating patients with no other therapeutic options outside of the clinical trial. Thus, several dozen patients with severe angina and/or heart failure have already been treated off trial in Thailand."

Link: http://www.genengnews.com/news/bnitem.aspx?name=1108101XSL_NEWSML_TO_NEWSML_WEB.xml

Alzheimer's And The Urge To Progress
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Modern Alzheimer's research is an example of the sort of success story that starts with determined patient advocacy and a few scientists, leading to a huge and well-funded research community, now close to cracking the problem. From the Enquirer: "much has changed over the past two decades. Today, there are four FDA-approved drugs available to temporarily relieve some symptoms of the disease. Even more encouraging are the advances being made in our understanding of Alzheimer's. Researchers are getting closer to conquering Alzheimer's, with breakthrough studies published almost weekly." Healthy life extension activists could do worse than to repeat the successes of Alzheimer's, AIDS and cancer advocacy in helping to create dedicated, well-funded research communities.

Link: http://news.enquirer.com/apps/pbcs.dll/article?AID=/20051120/EDIT02/511200360/1021/EDIT

Stem Cells, Statins
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It seems that at least some of the high-level benefits of statin drugs for heart disease patients may come from their effects on stem cells: "pravastatin, the generic name of one of the statins currently prescribed to lower cholesterol, increased the concentration of endogenous stem cells that may participate in cardiac repair independent of any cholesterol-lowering action. ... In addition, many newly formed myocytes -- heart muscle cells that aid in repair of damaged tissue -- were detected. While increased stem cells were seen after pravastatin in normal hearts as well, they only resulted in myocyte growth and development in diseased hearts." This is interesting; how many other treatments might have accidental stem cell contributions?

Link: http://www.medicalnewstoday.com/medicalnews.php?newsid=33769

Discussing Sir2, Sirt1 and Longevity
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Some interesting comments on the Sir2 gene - and the equivalent in mammals, Sirt1 - in relation to recent longevity research in yeast can be found in an ongoing discussion thread at the Immortality Institute. A large extension in life span in yeast was attained by deactivating the Sir2 gene - which is interesting, because previous studies suggested that overexpression of the mammalian equivalent (Sirt1) in mice was connected with an extended life span as a result of calorie restriction. It seems that studies on mice lacking Sirt1 have already been run:

Was already done in 2003 (1). What they found in the mice that were able to survive that despite growth defects and sterility that they shared some of the effects associated with long lived IGF1-deficient mice. It appears that Sirt1 has a developmental function and should not be altered during embryonic development. So the interesting question is why would Sir2 overexpression confer a modest lifespan increase but Sir2 deletion confer substantial lifespan extension? The clues could lie in which genes are silenced by Sir2/Sirt1. One gene that is silenced by Sirt1 is Foxo3a (2), a gene responsible for protection from oxidative stress (3) and DNA repair (4).

In any case, it would appear that if the life extension effects of Sir2/Sirt1 downmodulation are to be applied to mammalian systems they must be done so only in somatic cells (not germline or stem cells) and then only once development has been completed.

(1) Mol Cell Biol. 2003 Jan;23(1):38-54.
The mammalian SIR2alpha protein has a role in embryogenesis and gametogenesis.
McBurney MW, Yang X, Jardine K, Hixon M, Boekelheide K, Webb JR, Lansdorp PM, Lemieux M.

(2) Cell. 2004 Feb 20;116(4):551-63.
Mammalian SIRT1 represses forkhead transcription factors.
Motta MC, Divecha N, Lemieux M, Kamel C, Chen D, Gu W, Bultsma Y, McBurney M, Guarente L.

(3) Nature. 2002 Sep 19;419(6904):316-21
Forkhead transcription factor FOXO3a protects quiescent cells from oxidative stress.
Kops GJ, Dansen TB, Polderman PE, Saarloos I, Wirtz KW, Coffer PJ, Huang TT, Bos JL, Medema RH, Burgering BM.

(4) Science. 2002 Apr 19;296(5567):530-4.
DNA repair pathway stimulated by the forkhead transcription factor FOXO3a through the Gadd45 protein.
Tran H, Brunet A, Grenier JM, Datta SR, Fornace AJ Jr, DiStefano PS, Chiang LW, Greenberg ME.

Biochemistry is a complicated business, but there is clearly something of interest buried in the mechanisms connected to these genes. The bottom line would be whether or not scientists can establish a safe genetic change or gene therapy for adult humans that manipulates our metabolism to lead to significant extension of healthy life span. I should note that there is some debate and uncertainty over which of the six or more Sirt varieties in humans is actually the equivalent of Sir2, and whether what is true in mice is also true in humans when it comes to these mechanisms by which calorie restriction extends healthy life span. To throw another interesting result into the mix, one study suggests that Sirt1 in mice can act to reduce life span:

We showed that, unlike in yeast, mouse SIRT1 can function to suppress cellular longevity rather than to promote it. That has been a big surprise to the field since it does not fit with preconceived notions of the role of SIRT1.

That researchers can greatly extend life span in lower animals doesn't necessarily mean the same or similar mechanisms will do the same in humans - but that's what we're waiting to find out. Meanwhile, beyond the presently active and funded area of the genetics of longevity, calorie restriction and calorie restriction mimetics, there is a whole range of promising potential scientific anti-aging research - with far greater payoffs than metabolic tinkering could achieve - that is yet to take off or win the needed widespread support. In short, we could be moving forward to longer, healthier lives much more rapidly and directly than at present.

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More On Recent Longevity Research
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A post at Fight Aging! will give you the background on new and interesting research into longevity, metabolism and the Sir2 gene in yeast, but you'll find more at the Guardian: "When you do this genetic manipulation, you can get some of the longest lifespans [in yeast] ever described. We have good reason to believe this genetic effect is conserved in other organisms. We're working with mice and human cells now and are already starting to see the same response. ... When you start increasing lifespan by five or six times, it means you're really playing with the life and death programmes of organisms. We're telling the organisms to go into a completely different mode of slow ageing. What they're doing is saying 'I cannot afford to age. I still have to generate offspring, but I don't have enough food to do it now.'"

Link: http://www.guardian.co.uk/science/story/0,3605,1645418,00.html?gusrc=rss

Immune System Versus Cancer
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A rather clever approach to cancer immunotherapy is detailed at Medical News Today: "The vaccine, originally developed at Johns Hopkins, uses irradiated pancreatic cancer cells incapable of growing, but genetically altered to secrete a molecule called GM-CSF. The molecule acts as a lure to attract immune system cells to the site of the tumor vaccine where they encounter antigens on the surface of the irradiated cells. Then, these newly armed immune cells patrol the rest of the patient's body to destroy remaining circulating pancreatic cancer cells with the same antigen profile. ... Even though our results are preliminary, the survival rates are an improvement over most published results of pancreatic cancer treatment studies." It remains to be seen how effective this methodology can become - reliable treatments or preventions for cancer are an essential part of extending the healthy human life span.

Link: http://www.medicalnewstoday.com/medicalnews.php?newsid=33688

The Oblivion Question, Winning Essays
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The Immortality Institute has been running an essay contest on the Question of Oblivion:

How does one come to terms with the seemingly inescapable problem of oblivion after ones own death?

Or perhaps a more interesting question would be:

In the 70 years since Lomont first published his work, why has so little been written about the problem of oblivion after death?

Or perhaps the most ambitious question is:

Can science prove or disprove oblivion after death?

The two winning essays can be read at the Immortality Institute website:

Survival or Extinction?:

Can we survive our own deaths? Is there truly a life beyond there? Are we spiritually immortal? Or does it all end with our earthly demise?

These questions have ceaselessly preoccupied the able homo-sapiens since its very dawn. And why wouldn't they? Is there a more significant and urgent matter in light of the realization of one's own warranted mortality?

Questions of Oblivion:

A fundamental question that concerns human beings is "what happens to a person after death?" Over thousands of years, people in different cultures have lived as if they knew the answer - that some new form of existence begins after death. Beautiful artwork, intricate doctrines and elaborate funeral rituals attest to the importance of a profound and believable answer to the question. But in the present day we must ask, more than ever, whether our present-day scientific understanding of reality support the claims of many religions and philosophies that there is an afterlife, or does science instead offer convincing evidence that life ends in Oblivion?

Few people like to think about personal extinction and the absence of the self, which is unfortunate, because it slows the process of doing something about it. If you agree that gambling on the existance of an afterlife by dying is a bad or outright foolish idea - not to mention the suffering and age-related degeneration along the way - then shouldn't you be assisting groups working towards ways to dramatically postpone this fate?

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The Longevity and Metabolism Plot Thickens, Yet Again
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Recent work on the biochemical and genetic roots of the healthy life extension produced by calorie restriction leads us in a new and interesting direction:

By deleting a gene that has been linked to longevity in previous studies, scientists have produced one of the longest recorded life-span extensions in any organism, and opened a new door for anti-aging research in humans.

...

Scientists have known for several years that an extra copy of the SIR2 gene can promote longevity in yeast, worms and fruit flies. That finding was covered widely and incorporated into anti-aging drug development programs at several biotechnology companies.

...

Rather than adding copies of SIR2 to yeast, Longo's research group deleted the gene altogether.

The result was a dramatically extended life span -- up to six times longer than normal -- when the SIR2 deletion was combined with caloric restriction and/or a mutation in one or two genes, RAS2 and SCH9, that control the storage of nutrients and resistance to cell damage.

Human cells with reduced SIR2 activity also appear to confirm that SIR2 has a pro-aging effect, says Longo, although those results are not included in the Cell paper.

Since all mammals share key aging-related genes, the paper points to a new direction for human anti-aging research.

SIR2 -- and possibly its counterpart in mammals, SIRT1 -- may block the organism from entering an extreme survival mode characterized by the absence of reproduction, improved DNA repair and increased protection against cell damage, Longo suggests. Organisms usually enter this mode in response to starvation.

....

A "really exciting" implication, Longo says, is that cells may be able to speed up their DNA repair efforts. All organisms have the ability to repair harmful mutations in their DNA, whether caused by age, radiation, diet or other environmental factors. Cancer often begins when DNA mutations outstrip a cell's ability to remain differentiated.

Many researchers believe DNA repair systems are already running flat out. The organisms in Longo's experiment say otherwise.

The first caveat is that this research takes place in yeast - a great deal of good work comes from yeast studies, but there are as many differences as similarities between yeast and mammalian biochemistry. That said, this is most interesting, given the radical life extension achieved in this study - matching some of Cynthia Kenyon's worm experiments. I predict that we'll be hearing results of the same or similar sets of genetic tweaks in nematode worms and flies within a year.

The supposition on DNA repair is indeed exciting - but much more work needs to happen in this field in order to discover whether any form of significant healthy life extension technologies reside in the realm of tinkering with genes and metabolism in higher mammals. Given the size and longevity of whales, one would suppose there to be room for improvement for humans in there somewhere.

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Longevity Genes In Yeast
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Yeast and roundworms are where the search for longevity-determining genes often begins, as demonstrated in this EurekAlert piece: "Howard Hughes Medical Institute researchers and their colleagues have now uncovered 10 new genes that regulate longevity in yeast. The studies also suggest a new model for how aging is slowed when caloric intake is restricted. ... We'd like to understand how aging occurs in yeast. Even though yeast is a simple, single-cell organism, it's still capable of revealing mechanisms in the aging process. Similar genes may control aging in higher organisms, too. ... The two years of laboratory work, much of it done by Kaeberlein and Kennedy, were extraordinarily tedious, involving complex genetic and biochemical tests on a special collection of 4,800 strains of yeast cells developed by other scientists."

Link: http://www.eurekalert.org/pub_releases/2005-11/hhmi-run111605.php

Towards Biopacemakers
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EurekAlert reports further steps towards the creation of biological alternatives for artificial pacemakers: "In guinea pig experiments, Johns Hopkins scientists fused common connective tissue cells taken from lungs with heart muscle cells to create a safe and effective biological pacemaker whose cells can fire on their own and naturally regulate the muscle's rhythmic beat. ... Other biopacemaker technologies, Cho notes, use adenoviruses as part of gene therapy to carry pacing genes into the heart, or use combinations of gene- and stem-cell therapies that may cause cardiac inflammation or uncontrolled cell growth that cause arrhythmias instead of stopping them. ... It is very difficult to guide stem cells into forming exactly the kind of cell needed, but not so with fibroblasts."

Link: http://www.eurekalert.org/pub_releases/2005-11/jhmi-ctc111105.php

More Cartilage From Stem Cells
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Scientists have succeeded in producing cartilage from human embryonic stem cells. Regenerative medicine for cartilage is important, as this tissue is particularly difficult to heal or replace: "The research involved growing human embryonic stem cells with chondrocytes or cartilage cells, in Petri dishes in the laboratory in a specialised system that encouraged them to change into cartilage cells. When this was compared with just growing the human embryonic stem cells alone, the mixed stem cells and cartilage were found to have higher levels of collagen, the protein constituent of cartilage." Other groups have already succeeded in tissue engineering cartilage, but this new work would appear to be a helpful addition to our understanding of embryonic stem cells and ability to control their differentiation.

Link: http://www.imperial.ac.uk/P7061.htm

Cranks and the Impulse to Certainty
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Extending the healthy human life span is an endeavor that attracts more than its share of cranks; perhaps it's just that time of year, or maybe the rising profile of certain legitimate anti-aging ventures, but my inbox and the Fight Aging! comments have been especially busy of late. Vibrational devices to "change the voltage in your cells", vague promises of thrice-longer life in sheep from China, and more, mixed in with odd diatribes of all varieties. What is a crank?

"Crank" (or kook, crackpot, or quack) is a pejorative term for a person who writes or speaks in an authoritative fashion about a particular subject, often in science, but is alleged to have false or even ludicrous beliefs.

Science in progress via the scientific method is very much a matter of uncertainty, an often very slow and winding path to a consensus of theories and practical applications thereof, waiting to be overturned by the next great discovery. Humans crave immediate answers and certainties, however. It's unfortunate that the trait that leads to scientific investigation - the burning desire to know the answer as soon as possible, and thereby effect change in the world - is the very same trait that inspires the most harm to progress. A crank has taken that (internally) logical step to satisfy a base desire for certainty by creating "certainty" from thin air.

This certainty by revelation is the polar opposite of the scientific process; you know a crank because his or her work is unable to survive the scrutiny of the scientific community, professional and otherwise. The difference between a crank and a young upstart on his or her way to change a field of science is actually very clear: it lies in their engagement with the research community and ability to defend, improve and win acceptance of their work in the cut and thrust of the scientific method.

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Missing The Point, Part II
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An article from the BBC on radical life extension manages to avoid the Tithonus error - "It is argued that scientific advances in anti-ageing treatments means living longer will not place a burden on health care, because it will increase people's health span and not just add some extra years in a care home with little quality of life" - but falls right into the trap of assuming that retirement behavior will remain unchanged: "With retired people struggling by on an average income of about £11,000, more and more are going to live with their children because rising health, heating and council tax costs make it harder for them to keep their home." This is simply ridiculous - if you are an experienced, skilled 120-year-old and as fit, healthy and active as today's 50-year-olds, are you going to live in penury or go out and get a job?

Link: http://news.bbc.co.uk/2/hi/uk_news/magazine/4442020.stm

Contribute to Progress in LysoSENS Research
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The Methuselah Foundation, home of the MPrize for anti-aging research, is offering a new way for people like you and I to contribute to healthy life extension science. On the MPrize donation page, the latest option allows you to donate to LysoSENS or other SENS research.

What is LysoSENS? This is the first Methuselah Foundation funded research program to deal directly with removing age-related damage - in the form of accumulated lysosomal junk - from within cells, based on Aubrey de Grey's Strategies for Engineered Negligible Senescence (SENS). Hence the name, LysoSENS.

Cells have a lot of reasons to break down big molecules and structures into their component parts, and a lot of ways to do so. Unfortunately, one of the main reasons to break things down is because they have been chemically modified so that they no longer work, and sometimes these chemical modifications create structures that are so weird that none of the cell's degradation machinery works on them. This is very rare, but in the long run it adds up. The place where it adds up is called the lysosome, a special vessel that contains the most powerful degradation machinery in the cell; if something can't even be broken down there, it just stays there forever. This doesn't matter in cells that divide regularly, because division dilutes the junk away, but non-dividing cells gradually fill up with this stuff -- different types of stuff in different types of cell. The heart, the back of the eye, some nerve cells (especially motor neurons) and, most of all, white blood cells trapped within the artery wall all suffer from this. Eventually these cells can't take any more and they stop working right. This is the sole cause of atherosclerosis (the formation of lumps, called plaques, in the artery wall, which eventually burst and cause heart attacks and strokes). It is also important in several types of neurodegeneration and in macular degeneration (the main cause of blindness in the old). So it's very important to fix it.

Progress has already been made in the identification of bacterial enzymes that could do the job, but as de Grey notes: "We need a lot more work on this project. It will take time to find the right enzymes in the soil microorganisms, to find the ones that work well in mammalian cells and are not toxic, to modify them so that the cell knows how to target them to the lysosome, and so on. This is a project that is very 'parallelisable' - if lots and lots of laboratories work on it, it will succeed sooner."

If you find that funding research prizes for scientific achievement is not your cup of tea, I would hope that this direct funding of real anti-aging research is more to your taste. Please consider a donation to advance progress for a presently underappreciated pillar of SENS; just as for the MPrize, now grown to $3 million in cash and pledges thanks to many generous donors, every dollar and voice raised in support counts for a great deal.

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Engineered Blood Vessels In Trials
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WebMD reports on human trials of tissue engineered blood vessels: "This is the world's first implantation of a tissue-engineered blood vessel produced in the laboratory. ... The vessels are built with the patient's own cells ... blood vessels have either been grown or are in the process of being grown for six patients. Two have been implanted in kidney dialysis patients to offset damage in shunts placed in blood vessels of their arms used for dialysis. A third patient is expected to have the implant early next year. The team is able to take two cell types - skin and the inner lining of vessels - from the patient's own body. The skin is grown into sheets, wrapped around a medical tube, and fused together, forming a vessel. Just before implantation into the patient, cells grown from the inner lining of the patient's own veins are cultured and grown within the engineered vessel."

Link: http://www.webmd.com/content/Article/115/111636.htm?printing=true

AGE-Breakers In The News Again
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Progress on developing useful AGE-breakers - drugs capable of breaking down damaging chemical crosslinks and advanced glycation endproducts (AGEs) that accumulate with age - never seems to be as fast as advocates would like. Via Newswise, however, we have some signs of movement: "This is the first demonstration that this class of drugs, known as collagen-crosslink breakers, can turn back the clock and make old arteries behave like young ones ... These results confirm that this drug does have important effects on the aging process in the arteries, but we still have to prove that there's some benefit to patients in terms of reducing cardiovascular disease. Our next step will be a study, expected to begin in late 2006, of the drug's potential benefit at preventing or reversing heart failure in the elderly."

Link: http://www.newswise.com/articles/view/516084/

Better, Faster Dopamine Cells
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Sometimes the difference between promising lab work and viable basis for commercial therapy is a simple doubling of efficiency - infrastructure is at the heart of progress. Here, ScienceBlog reports on improvements in the production of stem cells to treat Parkinson's disease or similar age-related conditions: "For all of the promise embryonic stem cells hold for therapies for neurodegenerative diseases such as Parkinson's disease, they are notoriously difficult to use. One problem is in coaxing them into becoming brain cells that make dopamine, which is in short supply in the brains of individuals with Parkinson's. ... We have been able to show we could generate a process in the tissue culture dish that is simple, rapid, and uses defined reagents, most of which are human products. We can make them into dopamine neurons in a dish, and they are mature."

Link: http://www.scienceblog.com/cms/biologist_coaxing_stem_cells_to_make_dopamine_in_simpler_faster_method_9290

Both High Traffic and Intelligent, Coherent Comments - Shocking!
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I am shocked - shocked! - to discover a high-traffic blog in which the comments appended to a post on healthy life extension form a coherent, well-written, intelligent and readable discussion. My congratulations to the blogger in question for gathering such a community of readers.

I make no secret that I side with the anti-aging forces. Senescence is a horrible killer, a disease that should be fought with every available weapon. Every time I hear an argument about why humans should not artificially extend the number of years wherein we live robust, healthy, active lives, I get creeped out. "God wouldn't want us to do this" is the most irrational and disturbing, and holds no more weight with me than arguments about how transplants, artificial organs, or lifesaving drugs are "against God's plan." If you believe that stuff, great, you voluntarily forego life-saving, quality of life enhancing treatments. Just leave the rest of us alone.

But even worse in my view are creepy, death-embracing arguments like, "the world has too many people" or "all that is good in humanity comes from our mortality," which are morally bankrupt so far as I can see.

Go and read the whole thing, comments included.

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Stem Cell Plasticity, Brain Repair
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The Scientist looks at what can and can't be done with adult stem cells: "the scientific debate persists as to whether adult stem cells are multipotent, or if they even need to be in order to be therapeutically relevant. ... both authors came to similar conclusions about the implications of their findings. 'We both speculated that it may be serving a positive function in neurodegenerative disease, repairing tissues that are damaged,' says Blau, who notes that earlier studies in animals showed that tissue damage enhances bone marrow cell contribution. ... Wagers contends that even if bone marrow cells do in fact contribute to brain, the contribution is too low to be therapeutically beneficial. "But if you wanted to take an approach of trying to enhance that contribution, then it would be important to know the mechanism by which it was occurring.'"

Link: http://www.the-scientist.com/2005/11/7/20/1

Broadening Regenerative Medicine
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A great deal of interesting work is presently taking place in the broadening field of regenerative medicine - these are the barnstorming years, or at least as close to barnstorming as we're going to get in this overregulated environment. From News-Medical.net: "We are able to rescue neurons [from the results of a stroke] at a time when most research suggests they are already dead. ... The USF study challenges the notion that nerve cells inevitably die quickly in the core region of the brain most severely deprived of oxygen and nutrients when a stroke hits. Instead, the researchers suggest, many nerve cells within ground zero of the attack, like those in mild to moderately damaged outlying areas, may succumb over several days through a slower, more orderly process known as apoptosis, or programmed cell death. ... This delayed death would permit more time to deliver neuron-sparing treatments than originally thought."


Link: http://www.news-medical.net/?id=14421

Maximum Life Foundation
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I was reminded of the Maximum Life Foundation today, the brainchild of David Kekich, who you might recognize from the donor list for the MPrize for anti-aging research and his sponsorship of the Immortality Institute film, Exploring Life Extension. Kekich aims to craft a vehicle, a form of investment fund, to bridge the gap that presently exists between real anti-aging science, commercialization, and venture capital - a gap I touched on in a recent post. From the Maximum Life Foundation website:

Historically, significant financing for biomedical technologies in the U.S. has come from government-related and other private non-profit sources. Over time, the changing political economy has led to a shortfall of these traditional funding sources . This is especially true for life extension technologies targeted at maximizing longevity while maintaining a high quality of living.

For a while, private equity venture capital fund managers perceived this trend as an opportunity for venture capital placements. Some prominent successes have been achieved. However, this biomedical sector generally could not keep pace with the high returns obtained in ever decreasing time periods in other non-regulated (or less regulated) technology sectors.

Most venture funds, for example, have become increasingly impatient to harvest returns from their investments, many expecting an "exit" within only 2-4 years. This trend has been adverse for many biomedical technologies, since they generally have a much longer gestation cycle than communications, electronics or information technologies. In addition, many biomedical technologies require regulatory approvals, which further increases development costs and lengthens the investment cycle.

This is a real problem for the commercialization of longevity or real anti-aging research today. You either need philanthropic investors with a much longer time horizon and level of commitment to the end goal, or you need novel investment models that garner good enough backing, management and reputation to both lock up money for longer and deliver good returns over that longer time frame. At root, the problem is regulation - something that can only lead to slow progress, high costs and poor results. Here, you see part of the mechanisms that lead to this sorry result; when laws are created to make it hard and expensive to achieve worthwhile goals, then investment funds will pour away into other less regulated fields.

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Exercise: Still Essential
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We may not possess demonstrated, working anti-aging medicine (yet), but you and I still have a great deal of control over how much we cut our health and lifespan short through neglect and poor choices. As noted at EurekAlert, and should be plain common sense, exercise is a principle key to maintaining your health for as long as is possible. "The implications of our work are that not only will physical activity potentially add years to your life as we age, but the quality of those years is likely to be improved by regular physical activity." Given the rapid pace of biotechnology and medical research these days, why would you risk shortening your life and missing out on healthy life extension technologies that will be introduced in the decades ahead?

Link: http://www.eurekalert.org/pub_releases/2005-11/uoia-eay111005.php

Tithonus Fails To Materialize
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(Via IrishHealth). Healthy life extension means what it says - advances in medicine lead to longer lives, and also lasting health in later life: "data on hospital admission in older people in the UK and Europe has shown that older people do not spend a longer period in hospital in the decade or so before death compared to people dying younger. ... advances in medicine had allowed for the postponement of disabling illness when people get older. ... there is still huge untapped potential for postponing disability in old age in areas such as health promotion, illness prevention, the appropriate use of existing therapies and the feasibility of future technologies." This process of healthy life extension is presently ongoing in an incidental, indirect fashion - it is up to us to speed it up by ensuring that directed anti-aging research is funded.

Link: http://www.irishhealth.com/?level=4&id=8475

Scientific Thoughts on Aging
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From ScienceWeek, a grab bag of mainstream scientific thoughts on the mechanisms of aging; Klotho, oxidative damage, and senescence. "A defect in Klotho gene expression in mice accelerates the degeneration of multiple age-sensitive traits. The authors demonstrate that overexpression of Klotho in mice extends life span. ... overexpression of human catalase in the mitochondria of mice extends median and maximal lifespan by about 20%. Catalase prevents the formation of reactive oxygen species (ROS) that can damage cellular constituents. ... Cellular senescence is also thought to contribute to aging, although how it does so is poorly understood. In addition to arresting growth, senescent cells show changes in function. Because senescent cells accumulate with age, they may contribute to age-related declines in tissue function."

Link: http://scienceweek.com/2005/sw051111-5.htm

Rafal Smigrodzki on Actuarial Escape Velocity
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Researcher Rafal Smigrodzki (involved in the development of mitochondrial protofection, you may recall, a way to potentially replace age-damaged mitochondria in your cells) has made an interesting critique of the concept of actuarial escape velocity on the Gerontology Research Group mailing list.

I am warmly supportive of SENS in its general philosophy though I have many objections to various details, as may expected when dealing with ideas on the cutting edge. There is however one general issue related to SENS that keeps bothering me: the escape velocity.

If I understand it correctly, Aubrey, the escape velocity idea postulates that if the speed of average longevity increase from medical progress exceeds the rate of aging of the population, then the members of that population would be in effect immortal (modulo accidents &c).

Now, this may be true when you are talking about a population that doesn't have any age-related mortality to begin with - e.g. a cohort of babies who are born into a world where medicine continually races about 50 years ahead of their aging, eventually making them as likely to die from aging at age fifty as when they were babies, and maintaining this low mortality rate indefinitely (a simple shift of mortality curve without changing its shape).

But for the fifty year old, the situation is not so rosy anymore. At age fifty there is already an uptick in mortality, and as long as the speed of mortality reduction is not substantially higher than the speed of aging, the members of this cohort will indefinitely experience mortality at this (i.e. natural 50's) level, whether at age 70 or 100. Obviously, eventually you will run out of members of this cohort. The problem is even more severe for the 70-year olds, and hopeless for the really old ones - all this even with medical progress substantially faster than today.

This makes me doubt that SENS could lead to radically long survival in humans who are currently in their thirties or later - none of the proposed rejuvenation therapies is likely to kick in before they reach fifty or older, and to give them an average 5000 year span you would need to have much better than escape velocity progress.

Of course, if there are enough fifty-year olds being rejuvenated at escape velocity, some of them will live many hundreds, or even thousands of years - but the odds are, it would be neither you nor me.

This is not to say I am pessimistic about extreme longevity in general - I think that the first immortals are already alive, and most of them are babies, perhaps female, born recently in rich countries. It's just that for us, the old folks, something more than the escape velocity is needed.

Aubrey de Grey replies:

Your analysis is quite correct and your error is in your description of what the escape velocity idea postulates. Indeed, it is absolutely vital to avoid having even the average mortality rate of today's 50-year-olds for very long if one wants a good chance of living to 1000. But if you check my most widely-available description of EV (my PLoS Biol paper) you will see that that's exactly what I predict -- those who make it even by the skin of their teeth will be restored to truly young-adult health and mortality risk only a few decades therafter.

By the way, Chris Phoenix and I are collaborating on a computer analysis of the rate of arrival of rejuvenation advances that is required to keep a population's death rate from aging negligible, and the short answer is that for all reasonable assumptions that rate becomes absurdly slow in no time at all. I'll be presenting this work at the Biology of Aging Gordon Conference at the end of January.

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Healthy Aging IS a Contradiction In Terms
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There is no such thing as "healthy aging" - it's a misnomer, a myth put out by the lie down and die school of acceptance and suffering. Sadly, at the present time your only choices lie in how rapidly you allow yourself to degenerate due to age-related biochemical and cellular damage - but degenerate you will, no matter which of the presently available tools and techniques you use.

While health articles like this recent one in Forbes are good insofar as they go, they don't go very far at all. Far too much of the mainstream discussion of aging and health presents only steps one and two of healthy healthy life extension - basically good health practices and common sense - as the be-all and end-all of what can be done. This is far from true; in this age of ongoing biomedical revolution, the dominant contribution to the next thirty years of your health and longevity will come from the medical research pipeline. The future of that pipeline is entirely in our hands - the most important health choice most of us can make today is whether or not to materially support scientific anti-aging and longevity research.

Do you want to see a future in which all the diseases of aging, and indeed any ill-health resulting from aging has been banished? Do you want your future to be one in which "healthy aging" is not a contradiction in terms? If you don't stand up to say so, then this future is that much less likely to arrive within your lifetime.

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Building New Nerves
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Tissue engineering of nerves is moving forward nicely, as this News@UofT piece notes: "The design used coil-reinforced hydrogel tubes that promoted nerve regeneration equivalent to that of nerve autografts; a polymeric coil embedded within the wall structure of the nerve guidance channel created a reinforced polymeric channel that significantly enhances regeneration by ensuring that the tube stays open, allowing severed peripheral nerve ends to regenerate both inside and beyond the tube. ... What was innovative about this design was that it used a coil-reinforced hydrogel, a soft material. Nerve is a very soft tissue, and we wanted to match the mechanical properties of soft tissue to the channel we're implanting."

Link: http://www.news.utoronto.ca/bin6/051110-1795.asp

Mitochondrial Dysfunction, Diabetes
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From Medpage Today, an interesting look at the roots of age-related diabetes: "when type 2 diabetics have children, those offspring may get stuck with an inheritance of reduced mitochondrial activity in muscle cells. That, the researchers said, can lead to insulin resistance even when the progeny are young, lean, and have normal glucose levels. The finding adds to the weight of evidence suggesting that mitochondrial dysfunction in insulin-resistance pathways may play a major role in the development of type 2 [usually age-related] diabetes. ... These data provide new insights into the earliest defects that may be responsible for the development of type 2 diabetes."


Link: http://www.medpagetoday.com/Endocrinology/Diabetes/tb/2113

Stem Cell Trials Grow In Number
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Betterhumans notes another new trial of regenerative medicine for heart damage: "The trial is one of three ongoing studies in the United States to use bone marrow stem cells to treat chronic ischemia. The procedure will include harvesting stem cells from a patient's bone marrow, capturing the stem cells, and then infusing the stem cells through a coronary artery so that new blood vessels will grow ... The hope is the new blood vessels will replace or supplement those blood vessels that fail to adequately supply oxygenated blood to heart tissue ... Upon acceptance in the study, patients with blocked or damaged heart vessels will be assigned to one of three groups, each made up of three to four patients who will receive a preset dose of stem cell therapy."

Link: http://www.betterhumans.com/News/4879/Default.aspx

Video From the Immortality Institute Conference
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Randy Wicker, an interesting character, to say the least, has posted video of the Immortality Institute conference this last weekend.

On November 5,2005, one-hundred and fifty Immortalists gathered for their first conference at Georgia Technology Institute in Atlanta, Georgia, to hear visionaries outline how biotechnology, nonotechnology, cryonics, artificial intelligence and computer science could enable human beings to become the masters of their own fates.

...

The announcement of the first $1,000,000.00 donation toward establishing a scientific prize for extending longevity in mice was a historical landmark.

The most prominent speaker, Aubrey de Grey, Ph.D., Research Associate, University of Cambridge-SENS (Strategies for Engineered Negligible Senescence) outlined a detailed plan for curing human aging.

I had the opportunity of spending several hours with Dr. de Grey and two interviews with him will be interspersed with other highlights videotaped during this conference.

Depending on your system, you may have to download and rename the video file before you can play it.

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The Biggest Idea
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Healthy life extension is one of the "big ideas in science" listed by Salon: "Aubrey de Grey, a computer scientist turned biogerontologist at Cambridge University, predicts that some people now in their 60s will still be alive in the year 3000. De Grey is merely one of the more flamboyant members of a growing corps of scientists who believe we are on the verge of solving that quintessential aspect of the human condition, mortality. ... De Grey advocates an approach he calls Strategies for Engineered Negligible Senescence, or SENS, which involves attacking aging on every possible front: with genetic engineering, stem cells, telomere intervention, cloning, antioxidants and caloric restriction." Degenerative aging will one day be prevented and repaired with advanced medical technology - it is entirely up to us to ensure that this day arrives rapidly enough.

Link: http://www.salon.com/mwt/feature/2005/11/10/big_idea_science_list/

A Very Educational Exchange
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There is a school of thought that claims satire to contain a great deal more truth than any attempt at straight communication. It certainly seems to be much more revealing of character, goals and direction. If that is the case, then this post is a view of the more illuminating portion - the satirical portion - of the presently active public debate over healthy life extension within the gerontology community.

If you're new to this all, you'll find a little background on conservatism in gerontology both here at Fight Aging! and over at the Longevity Meme, alongside an introduction to the Strategies for Engineered Negligible Senescence (SENS). You may also recall that editor Jason Pontin of the MIT Technology Review is presently offering $20,000 for a coherent challenge to SENS.

But on with the satire. This piece from researcher Richard Miller is from the GRG mailing list and reproduced via transhumantech:

Dear Jason:

My colleagues have called to my attention the excited fascination with which the MIT Technology Review has been treating Dr. Aubrey de Grey's program to conquer aging. As you know, the SENS strategy delineates seven problems that from Dr. de Grey's perspective are the key components of aging, and suggests that they can be solved by a combination of stem-cell therapy, senescence-marker tagged toxins, allotypic mt-coded proteins, IL-7, total telomerase deletion, genetically-engineered, hormone-secreting muscle cells, and Phenacyldimethylthiazolium Chloride. Dr. de Grey has challenged gerontologists to debate the merits of the SENS program, and has expressed his opinion that we are now at or near a historical 'cusp;' those born after the cusp will be able to stay alive and youthful forever by adherence to the SENS strategy. Although Dr. de Grey's assertions have enjoyed wide circulation in the lay press, at scientific meetings, and in your own journal, it is fair to say that many experienced gerontologists still remain somewhat skeptical about his claims. Nonetheless, his success in developing such a well-regarded plan to solve the aging problem has prompted me to ask for his help on a similarly complex technological challenge. Alas, I have lost Aubrey?s phone number, and so I was hoping the MIT Technology Review might be willing to publish this open letter to him, along with these introductory remarks, as a public service to those of us who look forward to hearing his insights into problems of this kind.

Best regards,

Richard Miller
University of Michigan

==========================================================

Dear Aubrey:

I saw you on TV the other day, and was hoping that now that the aging problem has been solved, you might have time to help me in my publicity campaign to solve a similar engineering challenge, one that has been too long ignored by the ultra-conservative, fraidy-cat mainstream scientific community, the problem of producing flying pigs.

A theoretical analysis of the problem, using the fastest available modern
computers, shows that there are a mere seven reasons why pigs cannot, at present, fly.

1. They do not have wings.

2. They are too heavy to get off the ground.

3. The so-called 'law' of gravity.

4. They cannot climb trees.

5. Hair, instead of feathers.

6. They do not wish to fly.

7. They do not go tweet.

Although I have been too busy in my day job to find time to work in a laboratory, I have been able to show clearly that these problems can be solved, using an approach I call Plan for Engineered Porcine Aviation, or PEPA.

1. No wings: genetic engineering will be used to alter Hox-box promoters and micro-RNA gene enhancers to re-activate the pre-wing somite program. A dab of stem cell therapy might help here, too; at any rate, it cannot hurt, can it?

2. Too heavy: although the average pig cell is a chunky 20 microns in diameter, microbiologists have recently documented (R. M. Morris et al., Nature 420:806, 2002) free-living organisms as small as 0.8 microns in diameter. By the well known inverse cube law, a reduction in mean cell diameter of 25 will lead to a reduction in volume of 25^3 = 15,625, with a corresponding reduction in pig weight.

3. Gravity problem: This one?s easy ­ either move the pig to Phobos, one of the low gravity satellites of Mars, where people are going anyway and they can just drop the pig off on the way, or else use transient hypergravity attractivity to hollow out the Earth by removing the heavy and unnecessary core. As a side effect, if this is done properly, it just might speed up the Earth's rotation sufficiently to provide the pig with a bit of a push to get it started, too.

4. Can't climb trees: Who says pigs cannot climb trees? Because so far most of their food has been placed in troughs or in the undergrowth of French forests, pigs have not previously been motivated to climb trees. In any case, toxin-constrained nano-bonsai ought to do the trick here.

5. No feathers: the Drosophila antennapaedia gene, for which a Nobel prize was recently awarded, allows the transformation of bristles into legs or antennas, and there's no reason this wouldn't work for feathers and pigs, too.

6. Lack of motivation: easy to solve: LySergic Acid Diethylamide.

7. Tweet problem: implantable helium sacs, just under the armpits, so whenever they flap their wings a bit of helium gets squirted into their vocal cavity. I read an article about this in MIT's distinguished and highly respected alumni journal, Technology Review, so I know it can be done.

Although each of these strategies is based upon sound scientific precedent or fantasy, nonetheless some of my conservative critics here on the local faculty have argued, from their ivory tower, that no one has yet proven that any one of these methods has been shown to convert porkers to parakeets. But no one has yet tried all seven of them together, don't you see! In addition, funding for porcine avionics research has to date been very very low, due to the stubborn insistence of NIH on peer review. The PEPA program, however, has been endorsed, or at any rate not publicly pilloried, by dozens of eminent scientists whose names I could give you if necessary.

Amazing though it may seem, I believe that we are now at what I call a 'cusp' in the history of either porkiculture or aviation or both. Pigs born before April 14, 2009, will be destined to a life on the ground, rooting about for scraps, grunting unpleasantly, and constantly getting their curly little tails entangled in low-lying shrubs. Pigs born after April 15, 2009 (or perhaps a few days later), will in contrast waft lazily through the lambent skies, tweeting merry greetings to one another, nibbling at an occasional air-truffle, and enjoying panoramic views of either Cambridge or Phobos, depending. Also, they?ll get to live forever, by following the practices so stirringly depicted in your own articles.

All I need is a clever marketing gimmick ­ perhaps a prize of some sort, that will fool journalists and conference organizers into thinking that the only reason none of this works yet is that scientists are afraid to debate with me. Any advice?

All the best,

Prof. Richard Miller, M.D., Ph.D.
University of Michigan
Ann Arbor, Michigan

Here we have Aubrey de Grey's response in kind, also from the GRG list and via transhumantech:

My dear Rich, how delightful to hear from you. I am so heartened that you have chosen to dissociate yourself publicly from the anti-SENS sentiment recently expressed by some of our colleagues in EMBO Reports [November 2005 issue]. I hope you will succeed in extracting from them an apology for including your name in the list of authors (and even so outrageously parodying your inestimable writing style). Perhaps, since your name was midway down a long author list, they thought no one would notice.

What an interesting problem you raise. I confess I had not considered the hardship endured by pigs as a result of their flightlessness, but you articulate it most effectively. I think I can indeed help.

Before addressing the marketing aspect, I feel it is worth examining this problem for alternative solutions that may be even more straightforward than those you list -- and which may indeed be applicable to those unfortunate pigs who are already alive, so for whom your strategies 1, 2 and 5 are inapplicable. It would surely be best to alleviate as much porcine suffering as possible, so this would be a definite improvement. Further, since those who might fund your project are also already alive, this might facilitate marketing too.

In considering this question I have adopted the age-old strategy of looking to evolution for clues. Evolution has of course created flying creatures from flightless ones several times. However, most of these processes are thought to have been slow, progressing through long periods of aeronautical semi-competence that far exceed that of contemporary pigs. Moreover, almost all flying species share with birds most of the seven differences from pigs that you list. However, after much research I have identified a remarkable exception to this pattern. Amazing though it may seem, the little-known species Homo sapiens progressed, about a century ago, from a state of absolute flightlessness (unless we count floating, which you clearly do not count) to one of quite considerable competence at flying, and they did so over a period of only a few years. I am therefore inclined to look to the methods H. sapiens have adopted, as a starting-point for freeing our porcine friends from their current misery.

This approach seems most promising. The technique employed by H. sapiens involves no alterations to their anatomy or genetics, only the use of large prostheses. These "machines" are of essentially the same design when built to carry one organism or many, so should be rather easy to adapt for porcine use despite the anatomical differences between the two species. Further, my research indicates that in recent years H. sapiens has automated nearly all the operating procedures of these machines, such that a method for the pig passenger to express its desired destination may be all that is needed to complete the design.

This, however, brings me to perhaps the greatest challenge to either my proposal or yours, namely item six in your list of reasons why pigs remain so obstinately ground-dwelling. Pigs are well known to be among the more intelligent mammalian species. It is a sad fact that some of the brightest among us are inclined to presume that everyone else is stupid, such that when someone articulates an idea that they do not consider obviously correct they tend to dismiss it -- sometimes even ridicule it -- without bothering to familiarise themselves with the details. (Do you know, I once even encountered an American who thought so highly of himself that he believed he could outdo an Englishman at sarcasm!) As I'm sure you agree (and as I duly noted in my demolition of their piece in the same issue), your so-called coauthors in EMBO Reports are conspicuous examples of this flaw. Another case would be a learned immunologist's presumption that the word "allotopic" is merely a careless mis-spelling of the immunological term "allotypic", when in fact "allotopic" can trivially be looked up in, for example, PubMed. These individuals are also prone to resist debate on such matters, perhaps out of a subconscious reluctance to risk the possibility of being proved wrong. I therefore fear that the intended beneficiaries of your efforts may, by virtue of their intelligence (and awareness of it), spurn this chance to improve their lot; they may even refuse to entertain debate on whether the curious "engineering solution" we offer them will work. After all, the term "pig-headed" was not coined for nothing.

I am confident that this can be overcome, however. The clear feasibility of adapting for porcine use a technique used to such effect by another mammalian species can only be denied for so long; media exposure of the absurdity of the nay-sayers' position will bring the public around soon enough. After all, that position ultimately consists of arguments so laughable as that H. sapiens' methods will not work because the reasons pigs might want to fly (the air-truffles you mention) are not high on the H. sapiens agenda. Such tunnel vision cannot delude people for long, however great the supposed authority of its proponent -- we all meet our match some time. In particular, your characteristic eloquence on this matter, as exemplified in your letter, will surely suffice to sway the occasional billionaire to your cause, thereby circumventing the NIH conservatism you so rightly deplore. Best of luck!

Cheers, Aubrey

It should be noted that all these folks in the gerontology community have a fine working relationship with one another. The disagreements here are over what they (and I, and everyone else should) consider to be matters of great importance - can we cure aging, how soon can we cure aging, and how plausible are the proposed paths towards a cure for aging? If you found this satirical exchange as entertaining as I did, I would hope you are motivated to take a look at the serious side of the debate within gerontology over dedicated anti-aging research and healthy life extension.

To my eyes, there is a real danger of the "slowly slowly, it's impossible" school of thought winning out for another decade or two in this field, and that would greatly lower the chances of radical life extension occuring in our lifetimes. The way to avoid this fate is for us - all of us, working together - to ensure that funding is directed to plausible strategies, research communities and infrastructure dedicated to rapid advancement towards a cure for degenerative aging. The goal is most certainly possible, but only if we dedicate resources to making it so.

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Premature Aging And DNA Repair
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Accelerated aging conditions (such as Progeria or Werner's syndrome) have provided insight into the mechanisms of normal aging in the past. From the LEF News, a technical reprint on insight into DNA repair and aging-like processes of degeneration in Cockayne Syndrome, "an extreme form of accelerated aging that is inevitably fatal early in life. ... In this first in a series of papers on the mechanisms of [transcription-coupled repair (TCR)], Cooper and her colleagues have shed early light not only on how the mysterious process of [TCR] works at the molecular level, but also on the underlying cause of the transcription defects that accumulate after birth in Cockayne Syndrome, which result in cell death leading to CS's characteristic neurological decline and wasting. Further work may provide insight into the processes of aging itself."

Link: http://www.lef.org/news/LefDailyNews.htm?NewsID=2936&Section=AGING

Failing Stem Cells, Failing Arteries
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(From EurekAlert). A common age-related condition has been linked to age-related deterioration in your stem cells: "The progression of the artery-clogging disease atherosclerosis is linked to the inability of specialized bone marrow cells to continuously repair damage to the arterial lining ... It appears that the disease progresses as the body's intrinsic ability to repair and rejuvenate itself somehow becomes deficient. It is exciting for us think that if we as physicians could somehow stimulate or maintain a successful repair process in heart patients, we might be able to prevent the development of atherosclerosis even if we can't completely control other risk factors, such as high lipid levels or hypertension. ... The key is the body's reaction to tissue injury, which appears to be governed by certain sets of genes."

Link: http://www.eurekalert.org/pub_releases/2005-11/dumc-ivr110205.php

Progress Rests on Better Tools and Processes
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It's improvements in infrastructure - generally not all that flashy individually - that make all the difference to quality of medicine and speed of research, and infrastructure is built of tools and processes. Better tools and processes move medicine forward. With that in mind, here are two good examples of the type:

Quality control automation for tissue engineered arteries:

An MU researcher has created a device to find defects in tissue-engineered blood vessels. Mark Haidekker, an assistant professor of biological engineering, spent two years creating the machine, which reduces the production time and cost of creating these vessels. It is the first machine of its kind, according to Haidekker.

...

Each vessel is grown individually, making it a costly process; each needs to be constantly monitored without breaking the culture. Haidekker's machine can check vessels in the culture within a few minutes and is relatively inexpensive to make. It monitors the quality of the manufactured tissues and vessels by examining them for defects and alerts the screener to problems such as inadequate cell thickness, keeping defective vessels from being used in a patient.

The new parallelism in DNA testing:

Solidus Biosciences of Troy, New York, sandwiches drug candidates between liver enzymes on one microscope slide and cells from various human organs on another. The enzymes break down the drugs, exposing organ cells to the metabolites and revealing any toxicity.

In another, somewhat broader approach, a San Diego company called Kalypsys uses a robotic arm to fill 1,536 tiny wells with a mixture that includes human cells and up to 1.5 million different chemicals per day. The resulting data show toxicity, purity, and metabolic activity.

...

You really need to look at the big picture of what's going on in the body to know if a drug works," says Affymetrix's John Blume. "In the late '80s, we could look at eight or 12 genes at a time. Now we can look at more than 30,000."

Medical research and biotechnology are fields in the midst of energetic, complex revolution consisting of of tens of thousands of advances just like those above, making the formerly impossible reliable and cheap, step by step. This is the engine that enables us to plausibly discuss the creation of real anti-aging medicine in our lifetime.

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Stem Cells And Zebrafish
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Zebrafish are a popular option in basic biomedical research; this piece from This Week @ USCD gives an overview of one such research program: "Embryonic stem cell researchers are trying to coax pluripotent cells down a particular lineage. In order to do this efficiently and reproducibly, both of which are critical requirements of clinical use, one must fully understand the cues that cause cells to commit to one particular fate. ... Attempting stem cell therapy without this understanding could lead to a failure of therapy, or worse, an uncontrolled growth of cells commonly known as cancer. ... Current evidence suggests that most major organ systems are replenished by tissue-specific stem cell populations. However, at this point, the scientific community does not have enough information regarding the stem cell basis of every organ system to know if adult stem cells can be used instead of embryonic stem cells."

Link: http://ucsdnews.ucsd.edu/thisweek/2005/nov/11_07_stemcell.asp

Geron, Stem Cells, Spinal Injuries
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The Mercury News reports that Geron is looking to move embryonic stem cell therapies for paralysis from rats to humans, and is aiming at trials in 2006. "For its test, Geron proposes to turn human embryonic stem cells into the precursors for specialized nerve cells, called oligodendrocyte progenitor cells. Surgeons then would inject the cells into the spinal injury with the help of a special stabilizing frame the company has developed. If everything goes as planned, the progenitor cells would help form new axons and also turn into oligodendrocytes, which help form an insulating sheath for the axons, called myelin. The test probably would involve a few dozen patients, all of whom would have irreversible spinal injuries."

Link: http://www.mercurynews.com/mld/mercurynews/business/13102386.htm

An Overview Of SENS
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The latest American Aging Association Newsletter contains Aubrey de Grey's overview of SENS for biogerontologists - a good read for the rest of us too. "Possibly unaware of what he may be unleashing, Norm Wolf has asked me to outline in the AGE newsletter the approach to postponing aging that I have been developing for the past five years [1-3]. It goes by the acronym SENS, standing for 'Strategies for Engineered Negligible Senescence', and I have given it this provocative name without hyperbole: I claim that it genuinely has the potential to convert a species that ages (namely humans) into one that, at least within the limits of statistical detectability, does not." A high-profile exchange of views on healthy life extension is brewing in the gerontological community - a very good thing for those of us who wish to see more directed research into working anti-aging medicine.

Link: http://www.americanaging.org/news/oct05.html#SENS

An Interview With Robert Freitas
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Sander Olson was kind enough to point me to his two part interview (part one, part two) with Nanomedicine author and healthy life extension advocate Robert Freitas. Readers here will probably find the second portion of the interview to be more pertinent to advanced medical nanotechnology. Some excerpts:

If we combine the benefits of a human physiology maintained at the level of effectiveness possessed by our bodies when we were children (e.g., dechronification), along with the ability to deal with almost any form of severe trauma (via nanosurgery), then there are very few diseases or conditions that cannot be cured using nanomedicine. The only major class of incurable illness which nanorobots can't handle is the case of brain damage in which portions of your brain have been physically destroyed. This condition might not be reversible if unique information has been irrevocably lost (say, because you neglected to make a backup copy of this information). There are several other minor "incurable" conditions, but all of these similarly relate to the loss of unique information.

...

The availability of practical molecular manufacturing is an obvious and necessary precursor to the widespread use of medical nanorobotics. I would not be surprised if the 2020's are eventually dubbed the "Decade of Medical Nanorobots."

...

The greatest power of nanomedicine will emerge in a decade or two as we learn to design and construct complete artificial nanorobots using diamondoid nanometer-scale parts and subsystems including sensors, motors, manipulators, power plants, and molecular computers. The development pathway will be lengthy and difficult. First, theoretical scaling studies must be used to assess basic concept feasibility. These initial studies would then be followed by more detailed computational simulations of specific nanorobot components and assemblies, and ultimately full systems simulations, all thoroughly integrated with additional simulations of massively parallel manufacturing processes from start to finish consistent with a design-for-assembly engineering philosophy. Once molecular manufacturing capabilities become available, experimental efforts may progress from component fabrication and testing, to component assembly, and finally to prototypes and mass manufacture, ultimately leading to clinical trials.

As of 2005, progress in medical nanorobotics remains largely at the concept feasibility stage - since 1998, the author has published four theoretical nanorobot scaling studies, including the respirocytes (artificial red cells), microbivores (artificial white cells), clottocytes (artificial platelets), and the vasculoid (an artificial vascular system). These studies have not been intended to yield an actual engineering design for a future nanomedical product. Rather, the purpose was merely to examine a set of appropriate design constraints, scaling issues, and reference designs to assess whether or not the core idea might be feasible, and to determine key limitations of such designs.

If advanced nanotechnology and molecular manufacturing are of interest to you, then you should add the Responsible Nanotechnology blog to your watch list and make the time to read through the Foresight Nanotech Institute and Center for Responsible Nanotechnology websites.

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Biopaper For Tissue Printing
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(From deseretnews.com). The use of inkjet printers in tissue engineering is an intriguing adaptation of technology. Biological printing would of course benefit from biological paper: "A hydrogel or 'bio-paper' developed by a University of Utah College of Pharmacy professor is a key component of a $5 million National Science Foundation-sponsored study that includes organ printing. ... Think of taking a blood vessel - a cylindrical object - and trying to reconstruct it in 3D with two-dimensional slices ... He likens the resulting slices to a 'non-nutritious doughnut' with muscle cells on the outside and endothelial cells inside. To make the cylinder, those flat doughnut sections are literally printed, one thin layer of cells and hydrogel at a time, the platform moving away from the printer's 'bio-ink'-delivering needles as the cylinder grows."

Link: http://www.desnews.com/dn/view/0,1249,635158922,00.html

More Early Nanotech Versus Cancer
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Wired looks at how early stage nanotechnology - largely clever applications of improved materials science - will be employed in the fight against cancer, one of the many age-related conditions we must prevent or cure on the way to longer, healthier lives. "Nanotech gives us the opportunity to detect cancer tumors at 1,000 cells, whereas we're now seeing them at 1 million cells. By the time you detect some cancers today, there's no option of curing them, only of prolonging life. ... Researchers also hope to make particles that combine all these functions. 'We call this the mother ship. You can put multifunctional particles on it, like an aircraft carrier transports choppers and planes. It goes into the body, and if it encounters a suspicious region, finds out what that area is about and delivers the therapeutics.'"

Link: http://www.wired.com/news/medtech/0,1286,69206,00.html?tw=wn_tophead_1

Cancer Immunotherapy, Progress
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Via EurekAlert, news of one portion of the funding coming into immunotherapy research to cure cancer. "A pre-clinical research project [which] will advance understanding of how cancer cells evade the immune system, has been awarded nearly €12m by the EU. The European Union Framework Programme (FP6) will enable doctors to improve 'T-cell mediated immunotherapy', which has the potential to fight a broad range of cancers.
... an international consortium of 16 partners, who will collaborate on the process of engineering T-cells. T-cells are part of the body's immune defense machinery which naturally protects against infections and some cancers and can be used to treat some malignant disease, but many cancers avoid destruction by the immune system. The project team hopes that state of the art technologies can be used to modify the T-cells, to hunt down and destroy cancer tumours."

Link: http://www.eurekalert.org/pub_releases/2005-11/uom-meg110705.php

MPrize Versus *
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In light of the recent $1 million donation to the MPrize for anti-aging research - and the stellar progress of the prize throughout 2005 - I think it's well worth reading April Smith's repost of a debate over the merits of the Methuselah Mouse Prize versus other forms of funding for the future of healthy life extension:

We need a large amount of money, directed only at the actual prevention/reversal of aging. The problem with this is that nobody wants to fund it with venture capital because guess what... it takes a long time to see if people will die! As soon as a CR mimetic drug looks promising, for example if it looks like it can also be a cancer drug or some such thing, then all the capital goes into that, since a profit can be made right now, and the studies are shorter term. For example: Geron was founded by Michael West to exploit telomerase as the cellular fountain of youth. Venture capital got excited about this early on, because West put forward a powerful pitch at a crucial time (the early, optimistic inflation of the biotech bubble), but investors rapidly lost interest in the long term goals and began insisting that Geron be forthcoming with a drug get into the drug development pipeline post haste. So telomerase as anti-aging enzyme became telomerase as a target for inhibition as a cancer treatment. The same thing has happened to all of the biotech companies that have initially made their buzz by promising anti-aging drugs: Sirtris, Elixir, and all the way down.

Meanwhile, participants at the Immortality Institute forums are debating the merits of funding the MPrize versus buying more supplements:

I definitely go for the Mprize, but taking care of my personal health is just as important to me as my commitment to the 300. In any case, if you cant afford a continuous economical support to the Mprize, a single donation of any size is enough to add an extra voice to the list of voices against the horrors of aging.

Well, those members who haven't spent the weekend busy at the Immortality Institute conference, that is. The first pictures are already posted - fast work.

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Seven Percent, More Than Enough
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You can change the world if you can get even a few percent of the general population on your side at the beginning - many of the most successful advocacy campaigns of the 20th century started in the hands of a dedicated minority. Bearing this in mind, look at this recent poll reported in the Poughkeepsie Journal: "In the poll of 1,000 adults, health tops the list of fears about aging; it was listed by 78 percent of women and 68 percent of men. Other fears include the possibility of 'losing the ability to care for yourself,' cited by 75 percent of women and 66 percent of men, and the loss of mental abilities, 73 percent of women and 65 percent of men. ... On average, people become "elderly" at 71, the poll found, but except for the 7 percent who say they want to live forever, the average desired life span is 87." Everyone cares about health, but a sizable minority care about radical life extension, it seems. Good news.

Link: http://www.poughkeepsiejournal.com/apps/pbcs.dll/article?AID=/20051106/NEWS06/511060392/1006/NEWS01

Old Stem Cells May Be Harmful?
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Via PubMed, a study suggesting that old stem cells can be harmful: "Local injection of hematopoietic stem cell enriched cells, including mouse lin(-) cells, accelerates vascularization in animal injury models, apparently by release of angiogenic factors. Locally injected lin(-) cells from non-diabetic mice dramatically improve, but those from obese diabetic mice inhibit vascular growth in obese diabetic mouse skin wounds. ... Our data suggest that bone marrow-derived cells may be poor candidates for therapeutic use in older patients, and could actually harm such patients." Is this a function of the cells themselves, or a function of the environment they find themselves in? More research is needed, especially given the use of diabetes as a proxy for aging in this study.

Link: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16269529

Wisconsin Anti-Research Bill Vetoed
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As expected, and reported here by the Daily Cardinal, the state govenor has vetoed anti-research legislation that banned therapeutic cloning, a technology vital to much of the most promising stem cell research. "Although the bill banned human cloning, complaints arose over the bill's language, which opponents say did not distinguish between therapeutic and reproductive research. ... Everyone agrees that human cloning is not acceptable, but that's not what this bill was really about. This legislation was a very cynical way to try to scare people into stopping life-saving research that is going on at this university." After years of this, I still find it hard to wrap my head around a worldview that values small numbers of unthinking, unfeeling cells - no different than those you shed from your skin, in essence - more than actual human beings.

Link: http://www.dailycardinal.com/article.php?storyid=1027507

That Live Online Discussion With Aubrey de Grey
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You may recall I had previously mentioned the November 1st discussion with biomedical gerontologist Aubrey de Grey; if you take a look today, you'll see that the transcript is there. One of the interesting items for discussion is this:

Question from Mark Jones, U. Western Ontario, Canada:

Allow me to set the obvious ethical implications of your claims aside for a moment; can you give examples of the progress science has made already that persuade you to believe that the length of human life on earth can be extended so extensively already? In your opinion, this progress is not being held back by lack of scientific intelligence, so what do you believe are the reasons for the lack of progress in this area so far?

Aubrey de Grey:

I think that until recently the science of aging had not progressed far enough to let us design plausible interventions, but in the past 5-10 years it has reached that point. The main reason for lack of progress today is that most of the acknowledged experts in the biology of aging are being slow to take on board our improved understanding of what aging is and the available techniques to fix it. That's why I spend so much time debating these issues with my colleagues in biogerontology -- educating them, as I see it. When the biogerontological consensus "catches up with me" (as I see it), funding will be easy -- the public will believe aging is defeatable, so there will be votes in it.

Aubrey believes that the last generation did the best they were capable of, given the knowledge and tools to hand; I suspect that this is more of an open question. Could we have come further in the time we have had, if the resources had been applied and the will to cure aging existed? Or does slow progress of cancer research - up until fairly recently, at least - point towards fundamental limitations in our understanding of biochemistry and technological capabilities that have only recently been overcome?

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CIRM, Ongoing Woes
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The Argus looks at the continuing struggle over public funds and the California Institute for Regenerative Medicine (CIRM): "A year after California voters approved Proposition 71 to fund a $3 billion stem cell research program, the new state agency finds itself stymied by lawsuits and yet to issue a single dollar in grant money to scientists. ... In September, the institute approved 16 grants to scientific institutions, including $3.6 million to the University of California, Berkeley, during the next three years, to train scientists in stem cell research. But those funds can't be given out until the lawsuit is resolved and bonds are issued. The earliest estimate is January." Such is the fate of large public projects - endless waste and battle, as predicted.

Link: http://www.insidebayarea.com/argus/localnews/ci_3182178

Forbes On Mainstream Longevity Research
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This Forbes article looks at the funded (if not necessarily best in the long term) mainstream of aging and longevity research: longevity genes, metabolic tinkering, calorie restriction mimetics, and companies obtaining funding to follow paths only tangentially related to longevity. "The Nature papers caught the eye of Christoph Westphal, then at Polaris Venture Partners. He figured drugs stimulating the human version of sir2 (called sirt1) might harness natural defenses against diseases of aging. He helped raise $45 million to found Sirtris Pharmaceuticals in 2004 and became its chief. Westphal's team is now crafting compounds that have more potent sirt1-activating effects than resveratrol, hoping they might help tackle diabetes and Alzheimer's. The next crucial step will be extending the findings to people. Westphal says he has zero interest in developing drugs for aging."

Link: http://www.forbes.com/forbes/2005/1114/112_print.html

More MPrize News
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More news from the MPrize crew, with this from Executive Director Kevin Perrott:

Dr. Russ Hepple, one of the presenters at SENS2 who spoke about how caloric restriction helps preserve mitochondrial output in aged muscle has accepted the invitation to become an Advisor to the Mprize. Russ has been doing top work in the field of healthy life-extension and I am particularly pleased that his acceptance reinforces our mandate to be a global organization by the addition of a Canadian to our number. We are and will be grateful for his expertise when the need arises and are confident he will enjoy his association with us.

Many thanks Russ and welcome!

I should mention that Kevin Perrott is one of number of other Canadians amongst the volunteers, donors, supporting organizations and other folk who help out with the MPrize - it must be something in the air up North.

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$1 Million Mprize Donation
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The Mprize for anti-aging research has received its first million dollar donation - today is a good day for scientific anti-aging research! Let me be one of the first to thank the anonymous donor for his or her generosity and for greatly raising the level of vindication experienced by the Mprize volunteers and other donors. This is a big step forward for efforts to revitalize serious scientific progress towards a cure for aging and the end of age-related disease and degeneration. There is a long way to go yet - and more seven figure donations, I hope - but thank you, anonymous donor, for doing so much to push the best present day effort into the major leagues.

Link: https://www.fightaging.org/archives/000655.php

More Klotho Science
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Scientist continue to look into the klotho gene following earlier research suggesting its connection to longevity. Via EurekAlert: "The klotho gene, named after the Greek goddess who spins life's thread, is associated with preventing aging in mammals. The klotho gene product, or Klotho protein, is secreted in the blood and functions as an anti-aging hormone. A defect in the klotho gene in mice leads to a syndrome closely resembling human aging, while overexpression of the gene extends lifespan in mice. Now Makoto Kuro-o, assistant professor of pathology at the University of Texas Southwestern Medical Center at Dallas, has discovered one way in which Klotho extends lifespan. Using both cultured cells and transgenic mice, the researchers showed that Klotho increases resistance to oxidative stress."

Link: http://www.eurekalert.org/pub_releases/2005-11/asfb-ahr110305.php

$1 Million Donation Made To the Mprize For Anti-Aging Research
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Yes, you read that right: Mprize, $1 million donation, and I have it from Dave Gobel that the cashier's check just cleared today. Wow. This was somewhat out of the blue, and certainly far ahead of our expectations for progress in the rest of 2005!

Let me be one of the first to thank the anonymous donor for his or her generosity and for greatly raising the level of vindication experienced by the Mprize volunteers and other donors. This is a big step forward for efforts to vitalize serious scientific progress towards a cure for aging. There is a long way to go yet - and more seven figure donations, I hope - but thank you, anonymous donor, for pushing the best present day effort into the major leagues. From the press release draft (the final version should be out on the wires sometime following this post, and the Mprize website updated soon):

The anonymous $1 million donor cited a growing understanding of the real possibility of curing aging in our lifetimes as his reason for making such a tremendous investment. He first learned about de Grey's work from the popular press, even though most journalists take the easy path of characterizing de Grey - a respected, widely published figure in the scientific community - as an odd eccentric. The donor followed the Fight Aging! blog ( https://www.fightaging.org ) and the online newsletter of The Longevity Meme ( http://www.longevitymeme.org ), both advocates of de Grey's work and the Mprize in particular. In the Mprize, this donor saw a popular movement in the making, a movement of people who were not to be discouraged by the conservatism and lack of action in ivory tower gerontology. Every dollar in the prize fund represents a voice, calling for the scientific community to take the final steps towards real, working anti-aging medicine.

So, as many others have done, this anonymous donor realized that he could help the Mprize and thus help the fight against degenerative aging and age-related disease - medical conditions that claim more than 100,000 lives each and every day. So he sent a cashier's check to the address listed on the Mprize website - a check for $1 million.

I should extend thanks to our newest anonymous donor for increasing my personal levels of vindication as well. And once again, many thanks to everyone who has supported the Mprize over the past few years, building it to the level at which it can attract this sort of dedication from wealthy philanthropists.

As Mprize executive director Kevin Perrott said earlier, "Nothing is going to bother me today."

UPDATE: The press release is up at the MPrize site now.

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Exploring Stem Cells
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While not immediately relevant to regenerative medicine, research reported at ScienceDaily provides an interesting new take on stem cells: "it could be the case that at least some of the known adult stem cell types are 'only' the rudiments of earlier embryonal differentiation processes, or even dispersed leftovers from previous evolutionary stages. Indeed, these cells are still showing plasticity which is a characteristic of stem cells, but no direct physiological function can be deduced from it." So the many existing stem cell categories could each be complex, mixed groups of varied function and usefulness - as a rule, when biologists find additional complexity, they're usually on to something. Simplicity in biology is always suspicious.

Link: http://www.sciencedaily.com/releases/2005/11/051102174449.htm

Early Nanotech Versus Cancer
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Canada.com reports on the more promising and widespread approaches to the use of nanoscale engineering in cancer therapies: "The [study] involved engineering nanoparticles embedded with the cancer drug Taxotere. The particles were then injected directly into human tumours created from prostate cancer cell lines and implanted into the flanks of mice. ... The technology being tested involves a nanoparticle made of a hydrogen and carbon polymer with bits of drug bound up in its fabric and attached to a chemical that hones in on cancer cells. The polymer gradually dissolves, exposing the nuggets of drug little by little." Killing cells is easy, but killing specific cells is very hard. Accurate, targeted delivery is the hard problem of the day.

Link: http://www.canada.com/health/story.html?id=275b3e7f-4227-4ee1-ac63-889d00984f91

Organs, Heal Thyselves
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Lab Notes looks at how to go about making aged stem cells work once more: "The regenerative properties of organs are tied to the behavior of stem cells. So I focus on what happens to those cells with aging. Why don't they work anymore and can we fix them? ... The problem is that as the body ages, the molecules that regulate stem cells eventually change and inhibit their regenerative properties. Simply adding a new supply of stem cells to a damaged muscle, for instance, won't work because the foreign environment will interfere with the cells' behavior. ... They'll quickly stop repairing the muscle. But if you can supplement them with regulatory factors and also protect them somewhat from the aged environment, they'll behave better."

Link: http://www.coe.berkeley.edu/labnotes/1005/conboy.html

Aging and Reactive Oxygen Species, Some Science
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Via transhumantech, some pointers from researcher Joao Magalhaes on longevity and damaging reactive oxygen species (ROS, including the much maligned free radicals). Read the whole thing, but here's the bottom line from his point of view:

This seems to support the idea that ROS are not just damaging compounds, but essential biological molecules used in a myriad of functions. On this subject, I have a paper on ROS that could be of interest to some of you.

Lastly, here's another recent paper showing that antioxidant protection does not correlate with longevity in rodents, in line with many other results suggesting that antioxidant protection is already optimized in mammals.

In other words, attempts to improve human longevity through manipulation of antioxidant protection may not be such a great use of resources, but this is still a very complex area of study - like all biology - and not a settled answer yet.

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Inheritance of Telomere Length
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Randall Parker of FuturePundit uses a recent study of telomere inheritance as the starting point for a discussion of telomeres and longevity:

Telomeres are caps on the ends of chromosomes. They get shorter each time cells divide. As the telomere caps become really short they start to interfere with cell division. This is one of the causes of aging. Telomere cap shortening is probably an evolved mechanism to reduce the risk of death from cancer. Cancers need to undergo a mutation to activate telomerase to grow longer telomere caps so that the cancer cells can divide many more times than normal cells can.

Given that shorter telomere lengths probably reduce cancer risk it is by no means guaranteed that people who inherit longer telomeres from their father will live longer on average.

If you're interested in learning more about telomeres - and the current state of knowledge regarding their place in the complex biochemical relationships between aging, cancer and cell life cycles - you should take a look and follow the links therein.

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Michael Rose, The Long Tomorrow
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Biologist Michael Rose's work and book, The Long Tomorrow, are examined by the St. Petersburg Times: "Animals fed a nourishing diet containing 20 to 40 percent fewer calories than they normally consume will live about 20 to 40 percent longer. Apparently, flies that consumed less food diverted calories from egg production to fat storage, which kept them healthier longer. So fat promotes longevity? No, but caloric restriction certainly improves health and extends longevity in many species, including humans. When humans consume fewer calories, their blood pressure drops, their bad cholesterol declines, their good cholesterol increases, their immune function improves and the levels of insulin and glucose in their blood remain enviously low. But how does caloric restriction produce these benefits?"

Link: http://www.sptimes.com/2005/11/01/Floridian/Good_news_on_aging___.shtml