$36,000
$24,120

Yet Another Reason To Exercise

Exercise, good diet and lifestyle choices like calorie restriction have an enormous impact on the health you'll have later in life. While it most likely won't extend your maximum possible life span, avoiding cutting your health and life span short increases your chances of living to see working anti-aging medicine capable of repairing the cellular damage that causes aging - and thus enjoying a life of good health for even longer than you expected. Via the BBC, here's another reason - amongst the many - to take better care of the health basics: "The study of people aged between 43 and 86 began in 1988 and they were assessed every five years. ... after taking into account other risk factors such as weight, blood fat levels and age, active participants were 70% less likely to develop [age-related macular degeneration, or AMD] than those who did little exercise. It also showed regular walkers were 30% less likely to get the disease." Healthy is as healthy does: it isn't rocket science.

Link: http://news.bbc.co.uk/2/hi/health/6098782.stm

Stomping On Cancer With Viruses

Cancer has been prominent on the schedule here of late - rightfully so, as it's a big, bad problem we're going to have to solve if we want to enjoy any healthy life extension brought about by regenerative medicine, immune system repair and the like.

One of a number of approaches demonstrating progress of late is the use of viruses to kill cancer cells:

The new [therapy] uses a genetically-engineered form of the adenovirus, which normally causes colds. ... When injected into cancerous tumors, the virus quickly multiplies in the cancer cells and kills them, the team said. ... The new adenovirus can target only cancer cells and does not harm normal cells, the team said. ... Following three rounds of injections, more than 90 percent of cancer cells in the brains, liver, lungs and womb of mice disappeared within 60 days, the team said. Clinical tests will be carried out early next year and last 18 months.

It's scientific judo: find an existing biological system that does some or most of what you'd like to achieve, and tinker it into shape for the task at hand. Viruses are good at killing cells, are simple enough for modern biotechnology to manipulate, and can be made to be very selective. Here are another two teams working away at turning viruses into cures for the cancer that waits in your future:

New cancer-fighting virus kills invasive brain cells

Researchers funded by The Terry Fox Foundation and the Canadian Cancer Society have found that a cancer-fighting virus called VSV kills the most malignant form of brain cancer in mice.

...

The research team first modified the virus by altering one of the genes to make it safer in normal cells but still able to kill cancer cells. They then used a new way of delivering the virus - intravenously instead of directly into the tumour - and were able to target the main tumour as well as the tumour cells that had spread from the main mass.

...

"An ideal cancer-fighting virus should have effective delivery into multiple sites within the tumour, evade the body's immune responses, reproduce rapidly, spread within the tumour and infect cells that have spread. In this study, that's exactly what we found that VSV has done when injected intravenously," says Dr. Forsyth.

The researchers tested VSV on 14 cell lines of malignant glioma and found that the virus infected and killed all cell lines. The normal cell lines - those that did not contain malignant glioma cells - were not affected.

Mayo Clinic Cancer Center: Harnessing the measles virus to attack cancer

Mayo Clinic Cancer Center has opened a new clinical study using a vaccine strain of the measles virus to attack recurrent glioblastoma multiforme, a largely untreatable brain tumor. This is the second of several pending molecular medicine studies in patients using measles to kill cancer.

...

Many cancer cells, including glioblastoma cells, overexpress a specific protein, CD46, which allows tumor cells to evade destruction by the immune system. Strains of the measles virus, including the one in this study, seek out this protein, entering the glioblastoma multiforme tumor. Upon entry, the virus begins to spread, infecting nearby tumor cells and fusing them, which augments the effect of infection and increases cancer cell death.

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Towards Tissue Engineered Livers

Randall Parker comments on a recent advance in engineering liver tissue: "We cannot build a fullsized liver yet. That will take about 10 years. But this is the first important step. We expect this to really take off in the next 18 months or so. ... Livers are relatively simpler things to grow than 3 dimensionally more complex structures such as hearts and kidneys. So I'm expecting we'll see replacement livers before replacement hearts or kidneys. ... For a number of types of organs replacement to treat cancer might end up saving more lives than replacement due to accidents and other diseases. Got pancreatic cancer? Replace it. Got kidney cancer? Replace it. ... If a cancer is still contained within a single organ then an excellent solution might some day be to just replace that whole organ. ... We can develop the technology to grow replacement parts for just about every part of the body and this can be accomplished within the lifetimes of most of the people reading this. So why aren't we trying much harder?"

Link: http://www.futurepundit.com/archives/003846.html

A View of Rheumatoid Arthritis

(From EurekAlert!). Good, healthy science involves regular challenges to the present orthodoxy: "Why do nearly 95 percent of [rheumatoid arthritis or RA] patients have a common sequence of DNA, which scientists call a shared epitope, and why do patients with this DNA sequence have more severe forms of the disease than patients without it? ... Although the hypothesis that RA is an autoimmune disorder is widely accepted, there is no convincing evidence that it is correct. We see this same type of association [in] other diseases, which we know are not autoimmune diseases ... the shared epitope can trigger a signaling cascade that leads to increased production of nitric oxide [or NO] in other cells ... Overproduction of NO inhibits apoptosis - the natural process that leads to cell death. Resistance to apoptosis is a common trait found in cells lining the joints of RA patients, and is believed to lead to disease symptoms." To see quite different views - all backed up by good science - is an advance sign of more rapid progress towards a cure in the years ahead.

Link: http://www.eurekalert.org/pub_releases/2006-10/uomh-uso103006.php

NYT and WSJ On Calorie Restriction Research

Both the New York Times and Wall Street Journal rolled out articles on calorie restriction research today; more than that, they are representive of the mainstreaming of the will to a gentle, slow, modest form of healthy life extension as pushed by the folk behind the Longevity Dividend proposal. The New York Times first:

Many scientists regard the study of life extension, once just a reliable plotline in science fiction, as a national priority. The number of Americans 65 and older will double in the next 25 years to about 72 million, according to government census data. By then, seniors will account for nearly 20 percent of the population, up from just 12 percent in 2003.

Earlier this year, four prominent gerontologists, among them Dr. Miller, published a paper calling for the government to spend $3 billion annually in pursuit of a modest goal: delaying the onset of age-related diseases by seven years.

Doing so, the authors asserted, would lay the foundation for a healthier and wealthier country, a so-called longevity dividend.

While in general I'm all for raising public awareness of any plasticity of the human lifespan, we've all seen the objections to the Longevity Dividend; it is unambitious and slow, setting the bar so low that the target gains will probably happen anyway. It is the sort of lowest common denominator big tent approach that gets politicians to spend tax dollars on inefficient ways forward while ignoring the real possibilities of doing far better.

As I've pointed out in the past, the stage is being set for the same sort of conflict that occurred in nanotechnology in recent years. On the one hand, you have the larger group of moderates who support a slowing of aging via understanding and manipulating metabolic processes. On the other side, a smaller group of engineers who support the reversal of aging by repairing known forms molecular damage. The moderates - who are chasing large sums of public money from the government - may come to feel they must defend their inferior path against people with better plans and more ambitious targets. The nanotechnology fight was quite ugly; one can hope that it won't happen for healthy life extension science.

We all benefit when the atmosphere is one of friendly competition and may the best science win. At heart, the folk working on metabolic science have the right intentions:

“It’s a just big waste of talent and wisdom to have people die in their 60s and 70s,” said Dr. Sinclair of Harvard.

And just as big a waste in any following decade. Hopefully more people will come to see that in the years ahead - if 10 extra years, why not 20, or 30, or more? There is no age at which it is anything other than a tragedy that people suffer and die, with no help nor rescue.

But on to the WSJ piece, which - sadly - requires registration. A few interesting quotes:

A company that Dr. Sinclair co-founded in 2004, Sirtris Pharmaceuticals Inc., of Cambridge, MA, has begun testing a resveratrol-based drug in diabetic patients. It has raised $82 million from venture capitalists, a hefty sum for an early-stage biotech.

...

It faces competition from Elixir Pharmaceuticals Inc., also based in Cambridge, which Dr. Sinclair's former mentor, Massachusetts Institute of Technology biologist Leonard Guarente, co-founded in 1999 to develop drugs based on gene variants that slow aging. The niche also includes BioMarker Pharmaceuticals of Campbell, CA, and LifeGen Technologies of Madison, WI, both of which focus on mimicking CR with drugs.

The companies hope to develop therapies for diseases, not antiaging pills. One reason is that the Food and Drug Administration doesn't recognize aging as a problem warranting treatment. But if a drug could retard aging, it might delay the onset and possibly the progression of age-related diseases. "When you slow aging," says University of Illinois epidemiologist S. Jay Olshansky, "you push a host of diseases to later ages at one fell swoop -- cancer, heart disease, Alzheimer's, diabetes, as well as everything else that's negative about growing older."

The FDA issue makes my blood boil; it so distorts the entire process of funding, research and development that no meaningful non-philanthropic funding will be dedicated to directly attacking the problem of aging. This is not even to get into the ongoing disaster that government intervention has made of medical research in the US. High prices, forgone opportunities, vanishing investment. Such is the end result of repressive regulation.

If telomerase inhibitors were a new kind of computer chip, they would have been on every Wal-Mart pharmacy shelf and selling for ten dollars a bottle by now. ... In a free system, life insurance companies, consumer magazines, and other competing interests would provide medical databases. Maybe even the AMA would become a force for "truth-in-medicine," as it was to some degree before the creation of the FDA. Under common law but free of arbitrary regulation, drug development would be as fast as computer development. Cancer would be extinct and human beings would finally, really, own their own bodies.

But back to the WSJ piece; I think you'll find this interesting:

Dr. Sinclair later got another call from Mr. LoGiudice, this time inviting him to make a pitch for funding to one of Mr. Rasnow's wealthy acquaintances, Paul Glenn, a venture capitalist and a longtime supporter of research on aging. After Dr. Sinclair did so, the Glenn Foundation for Medical Research in Santa Barbara, CA, awarded $5 million to Harvard Medical School to launch a center on the basic mechanisms of aging with Dr. Sinclair as its founding director. Now plans are afoot to expand the center into a leading institute on aging, says Mr. Glenn, with start-up funding of $[75 - 100] million.

You should head over to the Paul F. Glenn Laboratories for the Biological Mechanisms of Aging and take a look; seems it'll be getting much bigger fairly soon.

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On Signing Up For Cryonics

Simon Smith of Betterhumans writes about the decision and process to sign up for cryonics: "I had already learned that cryonics is funded by life insurance, so, if you're young, you can get a pretty good deal on something that might save your life. You make low monthly payments and, should anything happen to you, the insurance goes to the cryonics organization responsible for your suspension. ... At the same time, I started the ball rolling with Alcor. They sent over some documents for me to complete, beginning with a declaration of my intent to be cryopreserved that would cover me legally - to a limited extent - while my life insurance and cryonics applications were being completed. And there's a reason for that. Getting cryonics life insurance and a cryonics membership is a lengthy process that's full of paperwork." There's room for improvement in there: a difficult sign up process is a real barrier to growth for any organization.

Link: http://www.betterhumans.com/blogs/simon/archive/2006/10/29/It_2700_s-official_3A00_-I_2700_m-signed-up-for-cryonics.aspx

Cancer Cells Are Different, So Target the Differences

We need reliable, low-cost, effective cancer therapies as a part of the next few decades of our attempts to live longer, healthier lives. Ultimately, we'll need something better than that - some form of fix or replacement for the very complex, fundamental cellular structures and mechanisms that make our cells work, but in the end lead to cancer - but it doesn't do to look too far ahead when you haven't yet fixed the first rung of the ladder. If the years ahead proceed much as I would expect, we'll see great gains in regenerative medicine and restoration of the newly-understood elderly immune system, amongst other advances. Just these alone will lead to more years of healthy life for average folk who generally took care of their health - and a large jump in the number of cancers in the population. Under the present cellular blueprint, the longer your body runs, the more likely it is to generate the unchecked, malfunctioning cells that cause cancer.

From the high level view - the view of building infrastructure and progress decade by decade - the most promising anti-cancer strategy of the moment appears to be a matter of finding and targeting the most obvious biochemical signatures that distinguish cancerous cells from healthy cells. There are a lot of them, as it turns out, of varying effectiveness. More are discovered with each passing month:

A new class of drugs - being developed by a major pharmaceutical company - targets an enzyme that helps cells divide; in cancer, this enzyme, called Aurora B, goes into overdrive, possibly leading to uncontrolled and abnormal cell divisions.

In essence, cancer cells are quite different. They act differently, and their biochemical programming is different. The breakneck pace of advance in biotechnology, driven by advances in processing power and the ability to engineer ever more effectively at the nanoscale, is now enabling researchers to take advantage of this fact. Firstly, scientists are able to cost-effectively identify actual, detectable differences between cancer cells and healthy cells. Secondly, scientists can cost-effectively design and produce complex molecules - drugs - to interact precisely with cancer cells in a given fashion. This second part of the equation was a tough and uncertain process as recently as 15 years ago; while still a challenge, it has become much easier in recent years. Given another decade of progress, turning out the design for a molecule to precisely perform a given biological task - with no side-effects - will be a short task that a researcher hands off to a computer.

On the practical drug engineering side, one very promising avenue of inquiry is based on the use of dendrimers, branching bush-like molecules that are not at all toxic, and don't trigger the immune system. The Wikipedia entry has a pretty picture, but the National Dendrimer & Nanotechnology Center introdution is somewhat more helpful.

Dendrimers are the first large, man-made molecules with precise, nano-sized composition and well-defined three-dimensional shapes. Current polymer molecules are long, spaghetti-like strands that grow in only two directions. Dendrimer molecules grow three-dimensionally by the addition of shells of branched molecules to a central core. The cores are also spacious and have “sticky” points on the outside to which various chemical units can be attached. By adjusting chemical properties of the core, the shells, and especially the surface layer, dendrimers can be tailored to fit the needs of specific applications.

Because you can easily attach an array of tailored molecules to a dendrimer - such as the drugs you have just designed to detect, interact with or kill cancer cells - it allows considerable efficiency in the development process. Knowing you have a safe way to hook together a cancer detector, a key to get inside the cancer cell, and the payload that will kill the cell, you can focus on making the best possible component parts of your new cancer therapy. Researchers are doing just this, and some of them are getting pretty good at it.

On the whole, I am optimistic on the prospects for the defeat of cancer. Resources are pouring into the field, and the trend in supporting and enabling technologies is towards accelerating progress. The long term solution will be tougher - but then, we'll be much, much better at this biotechnology business by the time that comes around to being next in the queue.

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Viral Infections and Memory Damage

The New Scientist looks at the evidence for damage to memory caused by viral infections across a lifetime: "A group of aggressive viruses, including those responsible for common colds, polio and diarrhoea, may harm a crucial memory-processing region in the brain known as the hippocampus, researchers say. The viruses, called picornaviruses, infect more than a billion people worldwide each year - people contract two or three such infections per year on average. ... This fact may explain the severe memory problems seen in some elderly people who do not have neurodegenerative illnesses ... repeated severe colds might possibly cause damage to this brain region that accumulates over a person's lifetime. [Researchers] plan to conduct brain scanning tests to look for signs of such damage in people with a history of acute infections." In addition to the buildup of damage over a lifetime, we can speculate as to the role of an increasingly ineffective aging immune system.

Link: http://www.newscientist.com/article/dn10359.html

Early Nanomedicine Versus Cancer

Early nanomedicine means the practical results of better nanoscale engineering, as opposed to medical nanorobots; the foundations for that advanced technology are still being planned and laid. From the Motley Fool, a look at how near term nanotechnology trends apply to the defeat of cancer: "In war, an ideal solution would be to have a 'smart' platform that could both detect and then eradicate an enemy. The same is true with cancer. And this leads us to perhaps the most significant nanotechnology-related development in the war on cancer: the creation of nanoscale devices that can both image cancer and then effectively deliver drug therapies. Essentially, the promise is to manufacture 'smart' devices that can detect unique cancer cells and deliver a drug molecule (or a more potent combination of different drug molecules) directly into the cancer cells. One such platform now under development is a dendrimer, and it is now being pursued by a couple of different companies."

Link: http://www.fool.com/news/commentary/2006/commentary06102726.htm

Philadelphia on Longevity Research

A Philadelphia Magazine article from earlier this year starts out in a similar vein to the recent New York Magazine piece on calorie restriction, but becomes more astute closer to the end: "While much of anti-aging research and its recent genetic breakthroughs is closely related to well-heralded advances in diseases like cancer or Alzheimer's, the field was something of a scientific stepchild for decades. That's partly a result of our own attitudes, our acceptance of what we see as the depressing but unavoidable course of nature. Ten more heart-healthy years? Sign us up. A 'cure' for aging? That's just silly. Absent a public push for an anti-­aging pill, there's been no billion-dollar incentive for the pharmaceutical industry to drill down on anti-aging efforts the way it does on age-related disease." Therein lies the real problem, the root of slow progress - and the reason I consider advocacy to be a worthwhile activity.

Link: http://www.phillymag.com/articles/top_doctors_2006_who_wants_to_live_forever

Calcium Hypothesis of Aging and Dementia

From EurekAlert!: "Diseases like Alzheimer's are associated with a loss of 'calcium-binding' proteins that protect nerve cells, said Moyer. Calcium is necessary for communication between neurons in the brain, and learning and memory are not possible without it. But too much of it leads to neuron death, interfering with memory and contributing to neurodegenerative diseases. ... Calcium-binding proteins decline with age, however, limiting the brain's ability to control or handle the amount of calcium 'allowed in.'" More work is needed to relate this mechanism to its cause. Where are those proteins going? Are the genes that produce them less active, or are they destroyed by other chemicals that build up with age? This researcher is looking at a replacement strategy: "Aequorin, the jellyfish protein, appears to be a viable substitute."

Link: http://www.eurekalert.org/pub_releases/2006-10/uow--ubr102706.php

Metabolism, Neurodegeneration and Repair

A recent release shows scientists pulling together varied threads of research into a view of aging, changing metabolism and neuron death in neurodegenerative disease. A number of different age-related neurodegenerative diseases involve a diminishing population of specific, essential cells in a small part of the brain. Parkinson's disease is one, and Huntington's - examined in this article - is another.

Their new evidence ties a metabolic defect to the loss of neurons in the striatum, the brain's "movement control" region. That neurodegeneration leads to the uncontrollable "dance-like" movements characteristic of the fatal, genetic disorder.

The researchers suggest that the selective loss of cells occurs because some parts of the brain are much more vulnerable to changes in metabolism. They also propose that the reduction in metabolic efficiency with aging - due to general molecular wear and tear, or other age-related conditions resulting from molecular wear and tear - contributes to the prevalence of neurodegenerative conditions in the old. In other words, metabolic decline is a necessary precursor.

As metabolic function generally diminishes in older people, such a connection might explain why many neurodegenerative diseases--such as Lou Gehrig's, Alzheimer's, and Parkinson's diseases, for example--tend to emerge and worsen with age

In the case of Huntington's, that decline comes from a genetic error that appears to mess up mitochondrial function - the essential process by which the body generates energy to power cells - hence young people can suffer the condition if that error is severe enough.

The problem, they found, lay instead in fat cells known as brown adipose tissue (BAT). In rodents, BAT is the primary tissue that controls body temperature. When the brain signals that the body is cold, the gene called PGC-1a increases production of a protein in BAT that leads the cellular powerhouses known as mitochondria to generate heat instead of energy.

In the BAT of hypothermic Huntington's mice, PGC-1a levels rose but failed to elicit the other events required to maintain normal body temperature, they found.

The link to mitochondria-regulating PGC-1a led the team back to the brain, and specifically to the striatum. That brain region is most affected in Huntington's disease and is particularly sensitive to mitochondrial dysfunction.

The researchers found that tissue taken from striatums of Huntington's disease patients and mice showed reduced activity of genes controlled by PGC-1a. They further found reduced mitochondrial function in the brains of Huntington's mice.

While scientists continue to work on uncovering the first cause of age-related changes in the body, there are intermediate term strategies for treating people who suffer from these very specific neurodegenerative conditions. One such strategy is to develop the technology to use embryonic stem cells to grow replacement neurons for those small populations in decline:

Unlike normal somatic cells, human embryonic stem cells (hESCs) can proliferate indefinitely in culture in an undifferentiated state where they do not appear to undergo senescence and yet remain nontransformed. Cells maintain their pluripotency both in vivo and in vitro, exhibit high telomerase activity, and maintain telomere length after prolonged in vitro culture. Thus, hESCs may provide an unlimited cell source for replacement in a number of aging-related neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease as well as other neurological disorders including spinal cord injuries.

Taming and understanding embryonic stem cells is the key to the next generation of regenerative medicine: any tissue for replacement in the body, produced on demand in a precisely controlled fashion.

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Rational Longevity

Anne C. explains what she means by rational longevity: "Supporting longevity research is acknowledging that there is nothing special about aging that makes it any less solvable than any other complex engineering problem ... There's a big difference between believing something will happen because it makes you feel better to do so, and having a goal in mind, not knowing whether it's possible or not, but being motivated to work to see if it is possible. Life extension science falls into the latter category for me. It isn't a fantasy or a daydream or an existential palliative. It's an experiment, and a project, and something well worth exploring. Whatever we can learn about anatomy and health represents data for the scientific memepool, which can translate to the potential for better lives for everyone, now and in the future."

Link: http://rationallongevity.blogspot.com/2006/10/what-is-meant-by-rational-longevity.html

The Power of Better Diagnostics

From Ars Technica, a look at the real might of improved diagnosics - often the first impact of new technologies. Don't overlook the power of identifying age-related disease early: it may not be as flashy as late-stage cures, but it's impressively effective for many conditions. "They followed over 30,000 individuals at-risk for lung cancer over a dozen years via annual rapid CT screenings. Of the 412 people who developed lung cancer over that time, the screening procedure allowed 88 percent of those cases to be caught at the earliest stage. Overall, the survival rate was over 80 percent in the participants who were caught early, but for those in this group who opted for surgical removal within a month of the diagnosis, the estimated 10 year survival rate is a staggering 92 percent. The eight patients who opted not to be treated were all dead by the end of the study. ... lung cancer [kills] an estimated 160,000 people annually in the US alone, where about 95 percent of those diagnosed with the disease currently die of it."

Link: http://arstechnica.com/news.ars/post/20061026-8081.html

Advances in Human Cryopreservation

Via the transhumantech list, signs of movement from the world of cryonics research:

Suspended Animation will be hosting a special meeting at the end of May, 2007 to disseminate important new information about cryonics research & development, and services.

Under the broad title "Advances in Human Cryopreservation," we will present progress reports from a wide range of sources including 21st Century Medicine, Critical Care Research, Suspended Animation, Alcor Foundation, The Cryonics Institute, and the American Cryonics Society. The presentations will be entirely new-not derived from speeches that have been delivered elsewhere.

From the rather attractive PDF-format meeting materials:

We will provide information about the most ambitious research plan in the history of cryobiology, describing stage one of an unprecedented effort to achieve reversible whole-body vitrification without the need for cell repair via [future] nanotechnology.

That's a pretty bold plan, given the current state of thinking on and practice of cryonics; I look forward to seeing more of the details.

As the attention of more of the older members of the healthy life extension community turns - sensibly - to cryonics, it will be most interesting to see how an increased flow of support and funding translates into research and a plan for future development, growth and professionalism. Younger folk can hope to engineer a future of rejuvenating biotechnology - such as that proposed by the Strategies for Engineered Negligible Senescence - that will rescue us before we die from old age. A good backup plan is a good backup plan, however, and we should be glad that a fair number of people are working on that.

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The Future of Dentistry

The near future of dentistry, as for many other fields of medicine, will prominently feature stem cells and tissue engineering: "Virtually all craniofacial structures are derivatives of mesenchymal cells. Mesenchymal stem cells are the offspring of mesenchymal cells following asymmetrical division, and reside in various craniofacial structures in the adult. Cells with characteristics of adult stem cells have been isolated from the dental pulp, the deciduous tooth, and the periodontium. Several craniofacial structures [have] been engineered from mesenchymal stem cells, growth factor, and/or gene therapy approaches. As a departure from the reliance of current clinical practice on durable materials such as amalgam, composites, and metallic alloys, biological therapies utilize mesenchymal stem cells, delivered or internally recruited, to generate craniofacial structures in temporary scaffolding biomaterials. Craniofacial tissue engineering is likely to be realized in the foreseeable future, and represents an opportunity that dentistry cannot afford to miss."

Link: http://jdr.iadrjournals.org/cgi/content/abstract/85/11/966

Calorie Restriction Science at Interdisciplinary Topics in Gerontology

The latest volume of Interdisciplinary Topics in Gerontology contains a brace of papers on calorie restriction - or dietary restriction (DR) as folk in that field call it - and its beneficial effects on metabolism. Some of the more interesting ones:

The Role of Hormesis in Life Extension by Dietary Restriction:

The level of food restriction that results in life extension and retarded aging in rodents also enhances their ability to cope with intense stressors. Moreover, this level of dietary restriction (DR) leads to a modest increase in the daily peak concentration of plasma free corticosterone, which strongly points to DR as a low-intensity stressor. These findings suggest that hormesis plays a role in the life-extending and anti-aging actions of DR.

Secrets of the lac Operon:

Elevated blood glucose associated with diabetes produces progressive and apparently irreversible damage to many cell types. Conversely, reduction of glucose extends life span in yeast, and dietary restriction reduces blood glucose. Therefore it has been hypothesized that cumulative toxic effects of glucose drive at least some aspects of the aging process and, conversely, that protective effects of dietary restriction are mediated by a reduction in exposure to glucose.

Anti-Inflammatory Mechanisms of Dietary Restriction in Slowing Aging Processes:

Underlying the beneficial effects of DR is the attenuation of system-wide inflammatory processes including those occurring within the central nervous system. During normal aging a progressive neuroinflammatory state builds in the brain involving astrocytes and microglia, the primary cellular components of neuroinflammation. DR attenuates the age-related activation of astrocytes and microglia with concomitant beneficial effects on neurodegeneration and cognition.

Dietary Restriction in Aging Nonhuman Primates:

Using rhesus monkeys (Macaca mulatta), an extensive array of physiological measures have been conducted in both males and females to evaluate the effects of DR. Monkeys benefit from DR with a lower body weight, body fat, blood glucose and thus are at lower risk for developing diabetes.

While metabolic science is an inefficient way forward insofar as healthy life extension is concerned, it is fascinating to watch scientists apply the new tools and knowledge of biotechnology to understanding the way in which we work. Calorie restriction in particular is an interesting field; many major metabolic mechanisms are altered very beneficially simply by eating less while still obtaining suitable levels of nutrients. There may be quite a number of separate processes that contribute to the overall benefit of practicing calorie restriction as a lifestyle.

It won't get us to radical life extension, but if you want to increase your chances of living into an era of working anti-aging medicine capable of repairing the molecular damage that makes you old, then calorie restriction looks to be a smart choice today.

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Inside a Stem Cell Trial

The Scientist takes us inside one of a number of trials of first generation autologous stem cell therapy aimed at regenerating the damage of heart disease: "More than 10 years ago, researchers isolated endothelial progenitor cells from the ranks of CD34+ cells derived from bone marrow or mobilized to the peripheral blood. This provided a rationale for the idea that CD34+ cells could induce angiogenesis. Human CD34+ cells have been shown to induce angiogenesis and improve cardiac function in a rat model of myocardial ischemia, and CD31+ cells, the pig analog of CD34+ cells, have been shown to do the same in that species. The Phase II trial Bergman is enrolled in follows a successful Phase I trial of the method in humans, using direct injection following catheterization because it can precisely target areas of ischemia."

Link: http://www.the-scientist.com/article/home/24908/

Funding and Success Attract More Funding and Success

Congratulations are due to researcher John Schloendorn and the Methuselah Foundation team:

The Biodesign Institute at Arizona State University has awarded biochemist John Schloendorn a $30,000 scholarship that will enable him to pursue anti-aging research as a Ph.D. student in the School of Life Sciences. Schloendorn is part of the institute's inaugural doctoral graduate assistantship class of 2006.

...

Schloendorn's research has been and is supported by a seed grant made by the Methuselah Foundation, a charity dedicated to accelerating the process of discovering methods to defeat the debilities caused by aging.

This is an excellent example of the way in which the combination of funding and success leads to more funding and greater success. Schloendorn has made worthy first steps in the search for bacterial enzymes that can safely degrade intracellular aggregates and thus remove their contribution to degenerative aging - and there will be more to come.

Schloendorn's work has led to the isolation and characterization of bacteria that efficiently degrade several recalcitrant cholesterol breakdown products, among them 7-ketocholesterol, that are thought to play a major role in atherosclerosis (the cause of almost all heart attacks and strokes). His future objective is to isolate the enzymes responsible for the breakdown and test their therapeutic prospects in cell models of the disease, with the ultimate goal of creating medical bioremediation treatments for humans.

In this way, by intelligently backing the right researchers and research programs, the Methuselah Foundation can multiply the impact of donations for SENS research funding by attracting outside resources to projects that are proving themselves successful. It's five figures this year, but it'll be more next, and yet more the year following. Momentum breeds more momentum.

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More Support For LysoSENS

The LysoSENS bioremediation research initially funded by the Methuselah Foundation is attracting more resources: "The Biodesign Institute at Arizona State University has awarded biochemist John Schloendorn a $30,000 scholarship that will enable him to pursue anti-aging research as a Ph.D. student in the School of Life Sciences. ... Schloendorn's pioneering work [focuses] on identifying microbes that possess particularly effective mechanisms to biodegrade the molecular 'junk' that accumulates inside cells over time, and is at the root of many of the debilities caused by aging. ... Schloendorn's work has led to the isolation and characterization of bacteria that efficiently degrade several recalcitrant cholesterol breakdown products, among them 7-ketocholesterol, that are thought to play a major role in atherosclerosis (the cause of almost all heart attacks and strokes). His future objective is to isolate the enzymes responsible for the breakdown [with] the ultimate goal of creating medical bioremediation treatments for humans."

Link: http://blog.methuselahfoundation.org/2006/10/methuselah_foundation_research.html

Arthritis and Surplus DNA

A new look at the roots of rheumatoid arthritis can be found at the New Scientist: "Mice that cannot degrade surplus DNA develop arthritis ... If the same occurs in humans, the discovery may suggest new treatments for the inflammatory disorder ... Not only did their joints develop the same inflamed, eroded appearance, but the characteristic chemicals humans produce when they have arthritis also turned up, including inflammatory signal molecules such as interleukins and interferons. ... Meanwhile, macrophages chock-full of undigested DNA accumulated in the mice's bone marrow, livers and spleens. Macrophages can signal to other cells to turn on inflammation, which is an important step in the body's fight against infection, but which when chronically activated in joints causes the symptoms of arthritis. ... The researchers conclude that macrophages gorged with DNA they cannot digest turn on TNF-alpha production, which leads to chronic inflammation in the joint, causing arthritis. The same thing may occur in humans."

Link: http://www.newscientist.com/article/dn10379-is-arthritis-caused-by-a-buildup-of-surplus-dna.html

On Lost Youth

You, like me, were young once. Leaving the vigor of youth behind feels like a great loss - especially after you've worked your way up to freedom, self-esteem and a life you like, but the only way your body wants to go is downhill, one failing piece at a time. Pining for lost youth is futile; it won't bring anything back. Putting aging out of your mind is self-destructive: you can't waltz through life in a state of willfull, unprepared self-delusion and not expect to run into trouble. Flailing around in the grip of airy promises made by the "anti-aging" marketplace is just as bad, and for a whole slew of similar reasons.

A thousand and one people out there in the world are trying their hardest to convince you they have a silver bullet that will prevent, slow or cover up aspects of degenerative aging. From the perspective of the radical life extension that will be possible in the years ahead, none of these folk are selling anything worth a damn.

Face the facts: you're not young anymore. Life is change, and making the best of today is not the same as making the best of yesterday. Fail to internalize that and you'll trash the present - and the foundations of your future - in the name of self-pity and nostalgia. Don't sacrifice yourself to the past; it's not as though you have to.

So what are you going to do about all this? What do you do with any failing machinery? If you're smart, you'll recognize that you are lucky enough to live in an age in which you can do more than rearrange your feelings about aging. The biotechnology revolution will deliver therapies capable of restoring your lost youth by repairing the molecular damage that causes aging - but it is up to all of us to determine the time that passes between now and the advent of this real rejuvenation medicine.

We can neglect advocacy and the support of determined, serious rejuvenation research, in which case progress will be slow - and many or all of us will age, suffer and die. But if we put our shoulders behind the wheel of progress, we have a chance at recapturing our lost youth - not just in our state of mind, but for real, in our bodies. Think about that.

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Another Targeted Cancer Killer

Cancer cells are different from normal cells in many fundamental ways. Inventive scientists are using those differences to build a wide range of targeted cancer killers. EurekAlert! has the scoop one of the latest: "a molecule containing long, double-stranded RNA is attached to epidermal growth factor (EGF) and delivered selectively to cells with an abnormally high number of epidermal growth factor receptors (EGFR). ... The nucleic acid-EFG molecule [is] avidly gobbled up by the multiple EGF receptors on the cancer cells, without harming normal cells. ... Normal cells, which possess 20 to 100 less receptors for EGF, are spared, since the amount of double-stranded RNA gobbled up is insufficient to induce them to die. The lethal RNA approach has been applied to mice in which human brain tumors were grown. The tests proved 100% effective in eliminating the tumorous growths." Effective, low-cost cancer therapies are an essential component of future longevity medicine - the more progress the better!

Link: http://www.eurekalert.org/pub_releases/2006-10/thuo-kb102406.php

DNA Repair Mechanisms and Aging

A new finding on DNA repair and aging is reporting at ScienceDaily: "cells in young fruit flies make use of a different mix of molecular DNA-repair mechanisms compared to cells in older flies. ... the reproductive cells of young flies tend to use the rough-and-ready repair processes that do not involve extensive DNA synthesis and do not require a matching DNA template for the repair. As the organisms age, however, the same kind of DNA breaks are repaired primarily by the slower but much more accurate methods that make use of a matching template. These findings raise the question of whether the rapid but risky methods of DNA repair used by cells of young individuals contribute to the accumulation of genetic damage, and perhaps to the aging process itself. Older cells may use the safer repair methods, but they still carry the genetic damage incurred during DNA repair in the fly's 'reckless' youth."

Link: http://www.sciencedaily.com/releases/2006/10/061024010423.htm

New York on Calorie Restriction

A slice of calorie restriction (CR) life in this article from New York Magazine; more than a little journalistic hyperbole and arrogance tops the feast (as we all know, the boundaries of the world lie at the limits of a journalist's preconceptions, and playing it straight doesn't sell papers), but the author gets the science mostly right: "Seat belts, vaccines, clean tap water, and other modern miracles have dramatically boosted average life expectancies, to be sure - reducing annually the percentage of people who die before reaching the maximum life span - but CR alone demonstrably raises the maximum itself. In lab studies going back to the thirties, mice on severely limited diets have consistently lived as much as 50 percent longer than the oldest of their well-fed peers - the rodent equivalent of a human life stretched past the age of 160. And it isn't just a mouse thing: Yeast cells, spiders, vinegar worms, rhesus monkeys - by now a veritable menagerie of species has been shown to benefit from CR's life-extending effects."

Link: http://nymag.com/news/features/23169/

The Nature of Biotech Progress

In noting yet another leap forward in bioinformatics, Randall Parker makes the following observation: "One (I think mistaken) argument made against the practicality of pursuing Aubrey de Grey's SENS (Strategies for Engineered Negligible Senescence) proposal to reverse aging is that the problems we need to solve in order to reverse aging won't become solvable in the next few decades. ... But I think these critics are missing an obvious reason why biotechnology can advance more rapidly ... The biochip reported above is able to speed up the collection of cellular metabolic information with a leap forward that is many times greater than the rate at which Intel co-founder Gordon Moore' predicted that computers would become faster. ... In a nutshell, we have the technology to do lots of small scale manipulations and measurements. Scientists and engineers who apply that technology to biological problems can therefore make huge leaps in the development of capabilities to study and manipulate biological systems."

Link: http://www.futurepundit.com/archives/003819.html

If Progress Was Easy, It Would Be Done Already

It's never all plain sailing in medical science, biotechnology and related areas of research that are of interest to supporters of healthy life extension. I don't generally look at the failures here or at the Longevity Meme - I assume we've all seen more than enough failure to know what it looks like, and that it is pervasive. I also assume that we know what follows failure for those dedicated enough to keep working: eventual success.

So it irks me that some of those who stand in opposition to scientific progress take the lazy shortcut of seizing upon a given failure and holding it up as evidence of impossibility. Bah. People failed to fly for a long time before they finally did, and a great deal of flying is happening these days.

Stem cell therapies - and indeed anything that involves manipulating exceedingly complex and not fully understood chunks of our biochemistry - is inherently challenging. There are failures all over the world, every day; this is how scientists learn.

The team injected the cells into the brains of rats, which had been given a chemical that causes damage similar to that seen in Parkinson's. The new cells integrated into the animals' brains and produced copious amounts of dopamine. As a result, the animals' motor coordination improved almost to the point of being normal, according to the report in yesterday's online edition of the journal Nature Medicine.

But when the animals were autopsied after three months and their brains were examined microscopically, the team found multiple tumors, indicating that some of the injected cells did not settle into the job of being neurons but rather had begun to grow uncontrollably.

...

Thomas Okarma, president of Geron, a California company that hopes to gain Food and Drug Administration permission to treat spinal-cord-injury patients with modified embryonic stem cells next year, said his company's cells have shown no sign of causing tumor growth in any of its animal studies.

But he said the FDA has asked for additional extensive data on exactly that question before it will give its final okay.

"What they worry about, and rightly so, is there are rogue undifferentiated cells lurking in the cell population that we haven't detected," Okarma said.

Geron cultivates its embryonic stem cells differently than others, he said, adding that no tumors have been seen in animals up to nine months after injections into the rodents' injured spinal cords. Moreover, he said, the cells survive and help the animals recover, in part by secreting special factors that spur new nerve growth around the injury.

Some people don't understand the nature of change, to the point of failing to see that success comes from clever persistence in the face of failure. Don't be one of those people, and you'll go far in life.

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Skin as a Stem Cell Source

It is straightforward to see that when useful stem cells can be generated easily, then research, the technology base, and the development of therapies will progress more rapidly. I suspect that, from the perspective of twenty years hence, the real value of adult stem cells and first generation autologous stem cell therapies will be in the technologies, infrastructure and experience gained from the exercise - especially experience in controlling the differentiation of stem cells into the desired type.

With this in mind, it has been educational to watch just how much scientists have been doing with stem cells taken from skin - from hair follicles, to be precise - over the past few years. My attention was drawn today to a proof of concept work in differentiating skin stem cells:

Nestin+ hair follicle-associated cells of murine skin can be isolated and differentiated in vitro into neuronal and glial cells. Therefore, we have asked whether human skin also contains nestin+ cells, and whether these can be differentiated in vitro into neuronal and/or glial cell populations. In this methodological pilot study, we show that both are indeed the case - employing purposely only very simple techniques for isolating, propagating, and differentiating nestin+ cells from normal human scalp skin

...

Therefore, human scalp skin can serve as a highly accessible, abundant, and convenient source for autologous adult stem cell-like cells that offer themselves to be exploited for neuroregenerative medicine purposes.

The near future of regenerative medicine is bright indeed. Enough funding and ingenuity are present in the field to see through a revolution in how we view and treat degenerative conditions.

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Better Antioxidant Systems

Via News-Medical.net: "it may be possible to use drugs to strengthen the anti-oxidant system in the brain as a treatment for presently incurable diseases like Parkinson's, Huntington's, and Alzheimer's and possibly other maladies. ... the new finding of a specific regulator of the body's own anti-oxidant system could lead to more-effective treatments for a number of diseases, and might even retard some of the effects of aging." Soaking up free radicals may be a cost-effective approach in this era of decreasing costs for drug discovery (setting aside the very varied effectiveness of different antioxidant strategies in animal studies), but it isn't the root of the problem - at least for age-related degeneration. The root is the mechanism by which excessive free radicals are being generated. As a general rule of thumb, long-term cost effectiveness is better obtained by heading off the root cause than by patching up after the fact.

Link: http://www.news-medical.net/?id=20654

Stem Cells Rather Than Drugs

The Korea Times reports on an early proof of concept for replacing some drugs with tailored cell therapies - and going beyond what can be done with drugs in the future. If you're trying to boost or restore levels of specific biochemicals in the body for proven therapeutic effect, why not put in place cells that can do the job? "Our team differentiated embryonic stem cells into nerve cells generating dopamine and serotonin while Dr. Cunningham devised a model of psychiatric disease for applying our technology, engrafting and evaluating approximately 80 animals. Then, the animals behaved as if they had taken anti-depressant medication. ... we are still at the initial stage and it will take a long time to apply them to a human being." A long laundry list of age-related and other conditions could be treated in this way once scientists have sufficiently developed the technology base.

Link: http://times.hankooki.com/lpage/200610/kt2006102219453668040.htm

Want To Make a Real Difference? Volunteer With the Methuselah Foundation

The all-volunteer Methuselah Foundation is presently a real growth opportunity in making meaningful longevity research a reality. Do you want to live a longer, healthier life? If so, keep your eye on the ball here.

The Thiel $3 million matching grant will see the foundation top $10 million in funding within the next few years, as it is filled by new donors. The first foundation-funded research in support of the Strategies for Engineered Negligible Senescence - fixing the molecular damage that causes aging - is underway and soon to expand. The Foundation chair, biomedical gerontologist Aubrey de Grey is well known and now has high-level fundraising cachet in addition to the attention of scientists and the media. The MPrize for anti-aging research is a reputable, high-profile research prize in a time at which research prizes are all the rage, well-understood and a popular cause. Aging and longevity science is presently undergoing a revolution in intent and capabilities. I could go on.

It has to be said - having been out there stumping for donors and publicity back when the Foundation was just the MPrize, and the fund was a mere $15,000 - that I'm damn impressed at how far this has come. So many similar efforts have failed, become sidetracked or never amounted to much - but the Methuselah Foundation has succeeded, and succeeded in making a mark. Succeeded because ever more people saw its merits and put their strength behind the wheel.

Have you noticed that we're up to 107 members of The Three Hundred now? There's another amazing success that has pushed the Foundation along from strength to strength. I'm happy to be in such august, forward-looking company - and may we live just as long as our names will.

All of this is stage one; as is so often the case, the years of hard work and donations are a matter of building an opportunity - of building a lever long enough to move the world, a horn loud enough to rouse the masses to action. And here it is, the chance of a lifetime.

Do you want to make a difference - a real difference - to the future of healthy life extension, longevity research and the bottom line of how long you are going to live? Then volunteer with the Methuselah Foundation! The next few years of expansion and endeavor - multi-million dollar fundraising, growing opportunities in research, raising awareness and much more - will need a larger volunteer crew than presently exists. If you have something to offer, jump on in and help make the future a better place for all of us!

I thought I'd leave the last word to Anne C.:

If there's one thing I've learned from all this so far, it's that there's no reason to think of yourself as someone who can't do anything, or that there are just special people in the world who get "chosen" to help out in certain areas. If you want to help out with something, or you think you have something to say, just put it out there and see what happens!

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Restoring Mitochondrial Function

From Science, a new method of potentially repairing mitochondrial function in cases of free-radical damaged mitochondrial DNA - and thus preventing the chain of events that turns a fraction of your cells into free-radical producing monsters that contribute to degenerative aging. Interestingly, this mechanism was discovered through examination of a class of disease causing parasite, Leishmania. A number of age-related conditions - and some fraction of aging itself - "are caused by mutations in mitochondrial (mt) transfer RNA (tRNA) genes. Kinetoplastid protozoa, including Leishmania, have evolved specialized systems for importing nucleus-encoded tRNAs into mitochondria. We found that the Leishmania RNA import complex (RIC) could enter human cells [where] it induced import of endogenous cytosolic tRNAs [and] restored mitochondrial function." Nicely done.

Link: http://dx.doi.org/10.1126/science.1129754

Producing Insulin-Producing Cells

Via Medical News Today, another step forward in the ability of scientists to control stem cell differentiation: "Novocell researchers report in the article a differentiation process that successfully engineers human embryonic stem cells (hESCs) into endocrine cells capable of producing insulin as well as other pancreatic endocrine hormones ... The in vitro differentiation process mimics normal pancreatic development in the body. ... The efficient, reproducible production of human embryonic stem cell- derived, insulin-producing endocrine cells through a process that mirrors the development of human pancreatic cells represents a critical step toward providing a renewable source of cells for diabetes therapy. This provides a foundation upon which we can build a standardized process for generating functional insulin-producing cells for the treatment of diabetic patients." Full control of stem cell differentiation will mean replacement tissue on demand for any damaged part of the body.

Link: http://www.medicalnewstoday.com/medicalnews.php?newsid=54627

Building a Better Meniscus

More on the tissue engineering of cartilage from Medical News Today: "The project aims to develop a tissue-engineered meniscus using tailored three-dimensional scaffolds and mesenchymal stem cells (precursors of the meniscus). ... The general wear and tear of normal life can cause damage requiring surgery. In fact, in any gathering of people, about 50 percent of the group will have a damaged meniscus and some may not have any meniscus in one or both of their knees. Unlike other body tissues, the meniscus does not repair itself because only a very small part receives blood, which is why surgery is often needed. While most patients quickly recover from a meniscusectomy, long-term issues such as early arthritis of the knee joint are common. ... The holy grail would be to harvest some mesenchymal stem cells from the patient, combine them with the scaffolds and appropriate growth factors and then insert this matrix into the knee so the patient effectively regrows their meniscus."

Link: http://www.medicalnewstoday.com/medicalnews.php?newsid=54668

Nanotechnology and Life Extension, Updated

Chris Phoenix, co-founder of the Center for Responsible Nanotechnology, dropped me a line to remind of past updates to the version of his essay "Nanotechnology and Life Extension" over at the Longevity Meme. After updating, I feel I should remind you folk that the article is just as good a read today as it was when first penned:

A few thousand years ago, people lived about thirty years. From their point of view, we have already extended our lives to an amazing degree. However, from where we stand today, we can see that we still have a long way to go. Some people still die in their 40's from cancer, heart attack, stroke, and infections. This is tragic, and frustrating. Today's medicine is only somewhat able to deal with these and other conditions--and it has barely started to attack the problem of aging. But we can see light at the end of the tunnel.

Fifty years from now, what causes of death will be preventable? That depends largely on the technology we will have available, so let's start by projecting some technology trends. Gene sequencing and identification will be as easy as a blood sugar test. Medical devices such as artificial hearts and insulin pumps will be implantable and well-integrated with the body's natural demands. Surgical instruments will be more delicate and less destructive; what today is "major surgery" will be done with an office visit. Computers will be millions of times faster than today's machines. Last but not least, we will probably have the ability to build strong, useful, complex machines out of individual atoms and molecules. This is called "nanotechnology" or simply "nanotech", and it will make us healthier in several important ways.

The prospects are bright for the decades ahead - if, that is, we can get our act together to leap the first hurdles in the fight to cure aging.

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Autophagy and the Aging Brain

Ouroboros walks us through the case for autophagy turning from good to bad as we age: "Previously, we've discussed autophagy as being on the side of the angels in the fight against cellular deterioration ... A new article in BioEssays [reviews] the evidence that in C. elegans, autophagy is responsible for the ultimate demise of neurons - the last holdouts against age-related decline, and themselves responsible for many aspects of genetic control of lifespan. ... Which is not to say that we should throw the autophagic baby out with the bathwater. It's quite conceivable that tissue targeting, timing of treatments, and other steps could be taken in order to make interventions based on autophagy an effective way to treat age-related decline. Rather, this is a reminder that too much of a good thing can be bad for you, and that autophagy is not always an angel. The devil is (as always) in the details."

Link: http://ouroboros.wordpress.com/2006/10/18/autophagy-on-the-brain/

Mitochondria and Neurodegeneration

As we now know, a complex chain of events causes faulty mitochondria to take over a small number of your cells as you age, causing them to spew forth damaging free radicals into your body. From a recent paper in Nature: "Many lines of evidence suggest that mitochondria have a central role in ageing-related neurodegenerative diseases. Mitochondria are critical regulators of cell death, a key feature of neurodegeneration. Mutations in mitochondrial DNA and oxidative stress both contribute to ageing, which is the greatest risk factor for neurodegenerative diseases. ... Thus, therapies targeting basic mitochondrial processes, such as energy metabolism or free-radical generation, or specific interactions of disease-related proteins with mitochondria, hold great promise."

Link: http://dx.doi.org/10.1038/nature05292

Fuzzy Discussion, But At Least They're Talking About It

I think that only good can come from more wide-ranging discussion of longevity, science and aging - and what can be done to help us lead longer, healthier lives. The more talk there is of healthy life extension, the more people will come to realize that real progress can be made in the next few decades ... rapidly enough to matter a great deal for most of those reading this today.

The funding needed for progress in the science of longevity is very dependent on public support and understanding. If there is no hue and cry, there will be no progress. Witness any number of achievements well within our capabilities as a civilization that have not come to pass - irrigation of the Sahara, colonization of the deepest ocean, and many more.

A couple of articles caught my eye today; examples that demonstrate the realization of healthy life extension as real science - just like any other modern branch of medicine - is working its way into the existing conversation about aging and society. It's but a few steps from there to support for a war on aging that looks much like the infrastructure and scientific culture dedicated to the defeat of cancer.

Scientists attempt to slow aging process:

In the last century the average lifespan has increased by about 30 years. Most people spend the last years of their lives in a fragile state, Anna McCormick, director of the biology of aging program at the National Institute on Aging, said at a recent conference on Capitol Hill. "We're trying to stretch the mid-life, not trying to add 15 years of very frail life at the end," McCormick said.

System must change as Britain gets older, says poll:

Among questions raised at the debate, titled "Three Score Years and…when" was that of eliminating chronic diseases, leading to hugely expanded longevity. Dr Aubrey De Grey, a Cambridge University geneticist and a self-confessed optimist, said medicine would at some stage be able to address ageing in the same manner as it tackled disease.

"We're within reach of genuinely fixing ageing," he said. If science eliminated age-related disease (defined as disease whose incidence increased with age) the upshot would be massively enhanced life expectancy, possibly within a few decades. Defeating ageing was a fundamentally only a maintenance problem, he said - the repair of ongoing and accumulating molecular and cell damage.

Plans were well advanced in this field, said Dr De Grey. "We can in theory control ageing as well as we can currently control malaria or HIV."

"In theory" here meaning after the investment needed to develop the Strategies for Engineered Negligible Senescence (SENS), and build the research infrastructure to carry forward from that point. More people should be thinking about these things - working towards a solution certainly beats the alternative of decay without hope.

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Vector As Kill Mechanism

Intriguing cancer research is noted at Seed; rather than using a virus as the vector to deliver anti-cancer gene therapy or other payload, the virus itself kills cancer cells: "South Korean scientists have said they have developed a new genetically altered strain of virus which is highly efficient in targeting and killing cancer cells. The new [therapy] uses a genetically-engineered form of the adenovirus, which normally causes colds. ... When injected into cancerous tumors, the virus quickly multiplies in the cancer cells and kills them, the team said. ... The new adenovirus can target only cancer cells and does not harm normal cells, the team said. ... Following three rounds of injections, more than 90 percent of cancer cells in the brains, liver, lungs and womb of mice disappeared within 60 days, the team said. Clinical tests will be carried out early next year and last 18 months." Impressive stuff.

Link: http://www.seedmagazine.com/news/2006/10/scientists_say_cancerkilling_v.php

Decoying AGEs

An interesting idea in a review paper from earlier this year: "The receptor for advanced glycation end products (RAGE) is a cell-bound receptor of the immunoglobulin superfamily which may be activated by a variety of [advanced glycation end products or AGEs] ... soluble RAGE (sRAGE) [lacks] the transmembrane domain and therefore circulates in plasma. By competing with cell-surface RAGE for ligand binding, sRAGE may contribute to the removal/neutralization of circulating ligands thus functioning as a decoy. Clinical studies have recently shown that higher plasma levels of sRAGE are associated with a reduced risk of coronary artery disease, hypertension, the metabolic syndrome, arthritis and Alzheimer's disease." If AGEs are binding to sRAGE instead of damaging your cells, this might just be a good thing - but not as good as getting rid of the AGEs in the first place.

Link: http://dx.doi.org/10.2174/092986706777585013

Study: DHEA Doesn't Work

From Yahoo! News: "Widely used DHEA supplements and testosterone patches failed to deliver their touted anti-aging benefits in one of the first rigorous studies to test such claims in older men and women. The substances did not improve the participants' strength, their physical performance, or certain other measures of health." If I've said it once, I've said it a dozen times - precious little to help your healthy life span is going to come from pills pushed by the usual suspects in the "anti-aging" marketplace. Oh, I'm sure they'll put their best foot forward to efficiently supply you with working AGE-breaker drugs, whenever such things arrive - but the anti-aging marketplace is presently a delivery system without anything to deliver capable of matching up to the hype. It's a grand cart constructed at great expense a couple of decades prior to the horse.

Link: http://news.yahoo.com/s/ap/20061018/ap_on_he_me/anti_aging_supplements

Reporting on the Alcor Conference

Mike LaTorra has posted his notes on the 2006 Alcor conference, held earlier this month:

  • Report on the Alcor Conference 2006 [Part 1]

  • Report on the Alcor Conference 2006 [Part 2]
  • I've been a member of Alcor since 2000, but this is the first Alcor conference I have attended. I was very impressed by the information in the presentations, the quality of the accommodations, and the smoothly efficient organization of the entire event. Alcor CEO TANYA JONES and her able helpers, both paid and volunteer, deserve kudos for a job well done.

    ...

    Back-to-back presentations by scientists BRIAN WOWK and GREGORY FAHY featured detailed reports on cryogenic research, including electronmicrographs of brain sections that allowed the audience to see how normal brain tissues compare with those that were frozen using different cryoprotectants. At some point the sheer volume of technical data, graphs and explanations began to freeze my brain without need of liquid nitrogen. Fortunately, both Brian and Greg are charming individuals who recognized that they were presenting to a mixed audience, not a gathering of their scientific colleagues, so they took pains to explain many of the background concepts needed so the audience could grasp the implications of their research.

    Then STEPHEN VAN SICKLE, Alcor Executive Director, gave a rather detailed report on the state of cryopreservation today and the future direction envisioned by Alcor. Vitrification research, which had already been explained by Drs. Wowk and Fahy, is the key element in the compound of improvements described by Van Sickle. Other elements include the development of improved emergency standby and transport equipment (some of which we would see later that afternoon during the Alcor site tour).

    Supporting the development and increasing professionalism of cryonics organizations is a sensible insurance policy for those interested in healthy life extension. Being cryopreserved is only the second worse thing that can happen to you - and you actually have some chance (albeit unknown) of coming back afterwards.

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    First Generation Stem Cell Therapies Spreading

    First generation autologous stem cell therapies are spreading more widely into trials and practice. VesCell is a good example of the type, and here are a couple of articles discussing the same class of procedure performed by an Indian group as an adjunct to more traditional heart surgery.

    City doctor first in Gujarat to perform stem cell therapy on heart patient:

    Announcing this, Dr. Thakore and Dr. Hemanshu Patel said that traditional technique using stem cells from bone marrow is quite prevalent, but they were the first to use stem cells from peripheral blood for the therapy. They have used it on five patients and the results are very impressive.

    Giving details of the technique, they said that blood is collected from the patient in a normal way and it is used to grow the required stem cells. Later, these stem cells are injected in to the affected part of the heart of the patient. This saves patient from painful and time consuming bone marrow technique.

    After stem cell therapy, these patients are raring to go:

    A few days after their angioplasties, Dr Shalin Thakore together with embryologist Dr Himanshu Patel, of the Krishna Heart and Super Specialty Institute, injected them with a drug “to allow mobility of stem cells from the bone marrow into the bloodstream.”

    About three to four days later, stem cells were cultured into cardiac stem cells and reinjected into the newly reopened arteries via another angiography.

    Lots of enthusiasm visible, as for VesCell and the work of other research groups. It'll likely be another few years before scientists will have enough data to say whether these therapies actually are effective (or cost-effective) for most people, however.

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    A Reminder of the Trend

    From WebMD a reminder that life expectancy has increased, is increasing, and will continue to increase in the future: "Life expectancy worldwide has been rising pretty steadily since 1840, at a rate of about two years per decade. In 1840, the longest-living people in the world were women in Sweden, and they lived an average of 45 years. ... James Vaupel, who directs the laboratory of survival and longevity at Rostock, Germany's Max Planck Institute, has written that advances in the prevention, diagnosis, and treatment of age-related diseases, such as heart disease and cancer, will usher in an age where every second child born in the industrialized world has an even chance of reaching the century mark. ... Although the belief that old-age mortality is intractable remains widespread, life expectancy is not approaching a limit ... Older people today are able to remain functionally independent much longer than in the past."

    Link: http://www.webmd.com/content/article/128/117137.htm?printing=true

    On Stem Cells Versus Parkinson's

    From AJC.com: "More than a million Americans who suffer from the debilitating neurological disorder Parkinson's disease are likely to be among the first to benefit from promising advances in embryonic stem cell research ... We want to replenish the population of nerve cells that are dying in the brains of Parkinson's victims. The encouraging recent scientific finding is that human embryo [embryonic] stem cells can be grown into the specific dopamine neuron that dies in Parkinson's, and we know that it can be transplanted and restore function in animal models [rats]. ... "If we manage to grow stem cells at will, we could have a supply that could help a large number of patients and reconstitute their [brain] circuitry."

    Link: http://www.ajc.com/news/content/news/stories/2006/10/16/1017brains.html

    Perspectives on a Decade of Research

    From Ouroboros, just returned from the 2006 CSHL Meeting on Molecular Genetics of Aging: "The meeting itself was at the same time exciting and grueling: There's so much happening in the field right now; one has the feeling of drinking from a firehose ... With a few days' remove from the experience, however, I keep returning to one theme: This field has exploded in the last dozen years. Without in any way meaning to denigrate the progress in study of aging prior the early 90's, the specific field in question at this conference (molecular genetics of aging) barely existed then. ... Starting in 1993, however, that began to change. ... I want to single out two papers that mark [for me] the beginning of the era of a true molecular genetics of aging. Both have had tremendous impact on the field over the ten years since - at the CSHL meeting, more than half of the talks were in some way based on the founding observations in these two papers."

    Link: http://ouroboros.wordpress.com/2006/10/16/molecular-genetics-of-aging-cshl-2006-perspectives-on-a-decade/

    Longevity Meme Folding@Home Team Update

    The Longevity Meme Folding@Home team members continue to make progress in the team rankings; well done all! We hit rank 300 only a few short months ago, and now the team has almost made it to the 250 mark.

    As you may recall, I sent around some momentos when the team hit rank 500 last year. I'll do it again at rank 200, so consider that an incentive and challenge - sign up for the team and get folding for better biotechnology and medical science!

    Better your spare computer cycles are going towards solving problems in medicine and biotechnology than sitting unused - so join our team and do that little bit more to help push science forward:

    What is protein folding and how is folding linked to disease? Proteins are biology's workhorses -- its "nanomachines." Before proteins can carry out these important functions, they assemble themselves, or "fold." The process of protein folding, while critical and fundamental to virtually all of biology, in many ways remains a mystery.

    Moreover, when proteins do not fold correctly (i.e. "misfold"), there can be serious consequences, including many well known diseases, such as Alzheimer's, Mad Cow (BSE), CJD, ALS, Huntington's, Parkinson's disease, and many Cancers and cancer-related syndromes.

    You'll find more information on results to date from the Folding@Home project at their website, such as those for some of the biochemistry of Alzheimer's disease (AD) and Parkinson's disease.

    We have many calculations being performed on AD. Our primary goals are the prediction of AD aggregate structure for rational drug design approaches as well as further insight into how AD aggregates form kinetically (hopefully paving the way for a method to stop the AD aggregate formation).

    Some of the team members keep a thread going at the Immortality Insitute forum; drop by and say hello if you plan to download the Folding@Home client and help.

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    Stem Cells Versus Nerve Damage

    The Independent reports on continuing efforts to develop stem cell based regenerative therapies for nerve damage: "Scientists have shown that human stem cells can be used to treat laboratory rats suffering from the same degeneration of the nerve cells in the spinal cord and brain that causes motor neurone disease in people. ... rats with the live cell transplants were able to retain their muscle control for longer than the second group of controls. A microscopic investigation showed that 70 per cent of the injected stem cells had developed into nerve cells and many of those grew nerve endings connecting to other cells in the rat's spinal cords. ... These stem cells differentiate massively into neurones - a pleasant surprise given that the spinal cord has long been considered an environment unfavourable to this type of transformation."

    Link: http://news.independent.co.uk/world/science_technology/article1876678.ece

    Understanding Notch Signaling

    Via the New York Academy of Sciences, an overview of some of the significance of the Notch signaling pathway: "In addition to its role as a gatekeeper of development, the Notch signaling pathway has been implicated in a number of disorders, including cancer, prion diseases, and multiple sclerosis. Notch's role in these disorders stems from aberrant activation of the pathway. In brain cancer, the Notch signaling pathway sets off the production of proteins that promote unchecked cell renewal. In prion disease, Notch activation causes atrophy of nerve cell dendrites and uncontrolled growth of other brain cells called astrocytes. In multiple sclerosis, Notch sets off an autoimmune attack against the brain via the overproduction of certain immune cells." If you look back in the Fight Aging! archives, you'll find more on the significance of Notch when working with embryonic stem cells. In order to effectively use stem cells of any stripe in more sophisticated therapies, scientists must gain better control over their differentiation and group behavior.

    Link: http://www.nyas.org/ebriefreps/main.asp?intSubsectionID=4321

    Cytotoxic T-Cells Versus Cancer

    A Newhouse News article sheds light on the present state of cancer vaccine research and development: an "immunologist's work with the human body's protectors, called cytotoxic T-cells, has led to an increasingly successful effort to develop a vaccine for breast cancer - one that, after injection, would actually eradicate the disease. ... Researchers at Advaxis are using a genetically engineered version of the common bacterium listeria to provoke T-cells to attack cancerous tumors. ... The challenge involved in designing a breast cancer vaccine is convincing our immune system to target the cells of our own body - and cancer cells are part of us - for demolition. With a clear understanding of how the immune system works, we might be in a position to create a vaccine."

    Link: http://www.newhousenews.com/archive/macpherson101106.html

    Progress Towards Viable Cancer Vaccines

    Since I pointed out an article on progress in cancer vaccine research over at the Longevity Meme today, I thought I'd follow up with a couple more here. Broadly, a cancer vaccine is a therapy that convinces the immune system to attack cancerous cells. A wide range of methods to accomplish this goal exist - and scientists have been very inventive in designing new ones over the past couple of years - but it usually boils down to making the immune system recognize one of the many biochemical cues only expressed by cancerous cells.

    Phase 1 Clinical Study On Potential Renal Cell Cancer Vaccine Successfully Concluded By Immatics:

    The study, which was conducted in six clinical centers in Germany, the United Kingdom and Switzerland, investigated the immunological efficacy of the therapeutic vaccine (secondary endpoint), in addition to its safety and compatibility (primary endpoint). Tests on 28 patients clearly showed that IMA901 was not only safe and well-tolerated, but in over 70 percent of the patients treated additionally evoked immune responses against tumor-associated antigens included in IMA901. Moreover, the formation of immune responses against multiple (>2) targets correlated significantly with a stabilization of the disease and a decline in the tumor burden identified prior to commencement of the treatment (p<0.05).

    immatics Chief Medical Officer Dr. Jurgen Frisch comments: "The results we achieved far surpassed immatics' expectations and are prompting us to lay the cornerstone for evidencing clinical efficacy by commencing a Phase 2 trial as early as possible."

    Immutep Immufact IMP321 Enters Phase I Therapeutic Vaccine Trial In Melanoma:

    Immutep announce that its lead product, ImmuFact IMP321 - a potent natural human T cell immunostimulatory factor designed to amplify the T cell immune response - has entered a Phase I clinical trial in disease-free melanoma.

    ...

    The primary objectives of the study are i) to determine whether immunization with 8 HLA-A2 peptides in PBS, or emulsified in Montanide, results in detectable cytotoxic T lymphocyte (CTL) responses in disease-free (absence of detectable melanoma lesions after surgery) melanoma patients when IMP321 is added as an immunological adjuvant and, ii) to establish safety of the addition of IMP321 to these two peptide formulations. Secondary objectives are to analyse the kinetics of any detectable CTL response and disease-free survival.

    A great deal of work is going into developing a working technology base for cancer vaccines: when one methodology can be shown to work effectively and reliably for one cancer, it can be expanded to many others.

    As I've noted in the past, extending healthy longevity requires widely available, highly effective, low-cost therapies for cancer. Like neurodegenerative conditions, cancer is a highly varied set of failure conditions in our most central biochemistry that becomes more likely with each passing year of life. Solutions will be needed as researchers begin to add the possibility of additional decades of healthy life by other means: those extra decades won't mean much if the ever-increasing risk of cancer catches you first.

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    Genetic Analysis, Aging, and More Folk Thinking About It

    My attention was directed to a paper I had missed:

    Each animal species displays a specific life span, rate of aging and pattern of development of age-dependent diseases. The genetic bases of these related features are being studied experimentally in invertebrate and vertebrate model systems as well as in humans through medical records. Three types of mutants are being analyzed: (i) short-lived mutants that are prone to age-dependent diseases and might be models of accelerated aging; (ii) mutants that show overt molecular defects but that do not live shorter lives than controls, and can be used to test specific theories about the molecular causes of aging and age-dependent diseases; and (iii) long-lived mutants that might advance the understanding of the molecular physiology of slow-aging animals and aid the discovery of molecular targets that could be used to manipulate rates of aging to benefit human health. Here, I analyze some of what we know today and discuss what we should try to find out in the future to understand the aging phenomenon.

    Here is a blog post with comments, as well as a few excerpts for those of you with neither a subscription to Nature Genetics nor $30 to hand:

    Recall that in an earlier post I noted that I have been giving some thought to the proposal that we ought to wage a war on aging itself. As I read through Hekimi's paper these issues came to me again. As a prioritarian I am of mixed minds about the prospect of such a war being waged, given the facts of scarcity and pervasive disadvantage. Much of course depends on what the proposed means of fighting such a war are, how proportionate our attention to this cause is relative to other pressing moral demands, as well as the likely magnitude of the benefits of waging such a war. I think such concerns inform, for example, the Longevity Dividend Campaign, hence the reason I support it.

    The more I think about the phenomenon of aging the more I realise that we need to critically assess our current attitudes towards aging and the effort to extend the human health span.

    I am always pleased to note the spread of people - of any socioeconomic tendency - talking seriously about healthy life extension in terms of research and the future. If we advocates could accomplish just one goal in the next decade, moving the broad discussion of aging from inevitability, skincare and diet - the focus on the useless and the nonsense of the now - to something more like the public discussion of cancer research and funding ... well, that would be a very big deal in and of itself.

    There is any amount of abstract support out there in the world for living longer, more youthful lives. But unless we can harness that support to concrete goals and knowledge - that science can produce real results in healthy life extension; that we must support and fund research to achieve those results - then it's no better than no support at all.

    But I think we can both change the conversation and make progress in other areas, such as funding research aimed directly at extending the healthy human lifespan. This is the way the world changes - through people setting out to make a difference, one by one.

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    Excess Weight and Arthritis

    Via Science Daily, a reminder that excess weight - and the lifestyle needed to maintain it - damages you in all sorts of ways over the long term: "research showed doctors diagnosed arthritis for 31 percent of obese adults and 21 percent of overweight adults said, compared with 16 percent of adults who were within acceptable weight norms ... A quarter of those who were physically inactive said they had doctor-diagnosed arthritis, compared with the roughly 20 percent of adults who were physically active." In addition to the chronic inflammation that comes from aggregations of fat, there's also the matter of exercise: less of it is demonstrably bad, helping put you into a downward spiral of conditions and limitations that both further damage your health and hinder you from leading a more healthy lifestyle.

    Link: http://www.sciencedaily.com/upi/index.php?feed=Science&article=UPI-1-20061013-08383900-bc-us-arthritis.xml

    CR and IGF-1 Signaling

    An interesting paper on calorie restriction biochemistry via PubMed: "Both life-long caloric restriction (CR) and the suppression of insulin-like growth factor-1 (IGF-1) signaling reliably extend the mammalian lifespan. The neuroendocrine system, regulated by the hypothalamus, remains the most convincing site of action for both these modes of life extension. Yet, determining whether CR actions are mediated by the modulation of neuroendocrine IGF-1 signaling remains unclear. ... while CR induces greater loss in the total number of cells in the [supraoptic nucleus (SON)] with age, it reduces the degree of age-dependent loss seen in [IGF-1 receptor (IGF-1R)] expressing cells. As a result, when compared to [old ad libitum fed] mice, the SON of [old calorie restricted] mice displays a greater proportion of IGF-1R cells and thus possibly enhanced IGF-1 sensitivity with aging." It's all pretty interesting, but remember that tinkering with metabolism is a dead end road - the gains will be minor and expensive in comparison to other ways forward.

    Link: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=17034982

    Gene Therapy For Parkinson's

    Good news from Medical News Today: "CERE-120, a gene therapy product in development for the treatment of Parkinson's disease, was was well tolerated and appeared to reduce symptoms by approximately 40% [as] measured by the Unified Parkinson's Disease Rating Scale (UPDRS) motor "off" score ... CERE-120 is comprised of an adeno-associated virus (AAV) vector carrying the gene for neurturin (NTN), a naturally occurring protein, whose role is to keep dopamine-secreting neurons alive and functioning normally." Promising gene therapy trials are now producing results much like those of promising drug trials: the path of every new, superior technology includes a period of time in which it comes up to par with the best of older technologies. Old-style drugs can't get much better - but gene therapy has hardly even started.

    Link: http://www.medicalnewstoday.com/medicalnews.php?newsid=53791

    AGE Breakers Beyond Alagebrium

    One of the ways in which normal metabolic processes degrade important components in your body (such as kidneys, heart, skin and blood vessels) is through the generation of advanced glycation endproducts (AGEs). Your body needs certain proteins in order to work properly; the creation of AGEs involves taking two or more of these proteins and sticking them together with chemical gunk, preventing them from doing their jobs. This is known as crosslinking; day in and day out, it is taking place in your body. Some AGEs are short-lived but common, growing or declining in population in response to your diet and metabolic peculiarities. Others are very long-lived or impossible for the body to break down; they build up over the years, and eventually there's enough of this gunk to seriously damage you.

    Problems caused - or not helped - by AGE buildup include kidney disease, and the many variations of blood pressure and heart conditions caused by a lack of elasticity in the tissues of heart and blood vessels. Diabetics in particular suffer due to more rapid accumulation of AGEs based on their metabolic biochemistry (e.g. high blood sugar, inflammation, free radicals).

    Fortunately, there are classes of chemical compound - drugs, in other words - that could break up the AGEs that are leading you part of the way towards age-related disease and eventual death. Predictably, they are known as AGE-breakers, and a number of companies have been involved in research and development in this field in the past five to ten years. Amongst them is Alteon, whose staff are presently attempting to gain regulatory approval of alagebrium (or ALT-711) based upon very promising animal studies and (unfortunately) not so promising human studies. I devoted a post to the company not so long ago.

    Alteon has gone through many of the reshapings common to young pharmaceutical development companies; the latest would seem to place them more in line for financial viability - and thus continuing development of ALT-711 for modest goals relating to the treatment of specific conditions. This is the sort of profile that maximizes the chance of attracting funding and clearing sufficient regulatory hurdles to make it to profitability.

    ...

    One might view Alteon and the development of ALT-711 as something of a transition from the old to the new in the community of folk seeking to extend the healthy human life span. It has its roots in the old school drug development pipeline and firm focus on supplements and things you can put in a pill. The aims, however, are well within the Strategies for Engineered Negligible Senescence (SENS), in that Alteon's founders and employees seek to effectively and deliberately repair a small portion of the cellular damage that cause age-related degeneration.

    There are many, many different types of AGEs, and researchers have no exhaustive catalogue of them all; any given AGE-breaker is going to tackle one subset at most. Alagebrium most likely attacks a type of AGE much more common in old animals than old humans, for example - which is why it works so much better for rats than us. Biotechnology has come a long way since alagebrium was first proposed and engineered, however, and a good thing too; scientists now have a much better grasp on which AGEs are most common, and thus must be broken to best help aged or diabetic humans. A compound called glucosepane is presently at the top of the list.

    In the extracellular matrix of the skin of a non-diabetic 90-year-old glucosepane accounts for about 50 times the protein cross-linking as all other forms of protein cross-linking.

    Legendary Pharmaceuticals is one small company chasing down an AGE-breaker for glucosepane; you might recall that founder John D. Furber gave a presentation at the SENS2 conference on the subject. From their website:

    Other damage affects extracellular proteins throughout the body, such as collagen and elastin. Recycling of these proteins proceeds slowly; they are out of reach of proteasomes and lysomes. Over time, they are chemically altered by reactive chemicals and sugars, which form covalent adducts and crosslinks. Crosslinked and glycated extracellular proteins contribute to many pathologies of aging and diabetes, including atherosclerosis, heart disease, stiffness, kidney diseases, arthritis, and erectile dysfunction. We are studying several promising mechanisms for breaking these crosslinks, as well as drugs which quench reactive free-radicals before they can chemically damage the proteins.

    I should note that the company website also has a rather good resource page for glycation and crosslinking of proteins if you'd like to learn more about the chemistry and consequences for your health:

    Glycation changes the shape and properties of proteins. Crosslinking reduces the flexibility, elasticity, and functionality of the proteins. Furthermore, the chemical modifications of glycation and crosslinking can initiate harmful inflammatory and autoimmune responses. "AGE and nonenzymatic crosslinks are demonstrated to signal inflammatory cytokines, extracellular matrix expansion, angiogenesis, and growth factors." [deGroof] Glycation has been found in connective tissue collagen, arterial collagen, kidney glomerular basement membrane, eye lens crystallins, nerve myelin proteins and in the circulating low-density lipoprotein (LDL) of the blood. [Bucala]

    Over on the other side of the world, a fair-sized Indian company called Torrent Pharmaceuticals has been working on AGE-breakers for a while:

    Of the 7 research projects currently in pipeline, 3 are focussed on Diabetes. The first of them is Torrent Pharma's patented Advanced Glycosylation End-products (AGE) breaker compound, which has great potential for the treatment of diabetes related vascular and cardiac complications. This proprietary molecule has the promise of a block-buster in the offing.

    You'll have to do more digging on the Torrent website and related sources if you want to find out what it is, how it performed in animal tests, and how soon in might be heading to trials and the marketplace. I leave that as an exercise for the interested reader.

    The bottom line: there is an opportunity to greatly affect the aging process here, using the huge, existing drug development and marketing infrastructure - if the right compounds can be identified and constructed in a cost-effective fashion. Modern biotechnology is becoming ever better at doing just that, and funds are presently invested in the task - albeit not as much as we'd all like.

    I expect the largest hurdles to a glucosepane AGE-breaker in the next 10 years to be regulatory, just as they are for every other aspect of medicine these days. Isn't it nice to live in a society in which so much effort is devoted to ensuring you won't live to see healthy life extension technologies?

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    PBS Tissue Engineering Interview

    A transcript of an interview with tissue engineer Anthony Atala can be found at PBS: "You know one of the major challenges today in the field of regenerative medicine is the resources that we have available to really bring these technologies together. It takes enormous amounts of, of uh, funds to actually get these tissues to look and act normally and that is just in a laboratory. It takes yet another large investment to be able to bring these tissues on the bench to the bedside. ... I think that there should be a massive regenerative medicine project, a nationwide effort to really try to accelerate these technologies to patients. The issue at hand right now is that the technologies are there. We already know that the potential is there." A good rule to live by: no realistically attainable amount of funding is ever "enough."

    Link: http://www.pbs.org/newshour/bb/health/july-dec06/atala_10-11.html

    The Memetic Success of Calorie Restriction

    As a recent general interest health article illustrates, the practice and benefits of calorie restriction (CR) are enjoying a newfound spread of understanding in wider culture. It wasn't more than a few years ago that CR was very much on the fringe, known and practiced by only a few. Now, CR is marked by its absence in any common sense article on good health practices.

    Rats fed 30 percent less than normal live 30 percent longer than usual -- and in a recent study at the Washington University School of Medicine in St. Louis, the hearts of the leaner human calorie-cutters appeared 10 to 15 years younger than those of regular eaters. In other research, calorie restrictors improved their blood insulin levels and had fewer signs of damage to their DNA. Eating less food, scientists believe, may reduce tissue wear and tear from excess blood sugar, inflammation, or rogue molecules known as free radicals.

    Edward Calabrese, Ph.D., and Mark Mattson, Ph.D., have opted for "calorie restriction lite."

    Calabrese, a professor of toxicology and environmental health sciences at the University of Massachusetts, Amherst, dumped the midday meal. Mattson, chief of the laboratory of neurosciences at the National Institute on Aging, has done without breakfast for 20 years.

    Try it

    Skip a meal a day. You don't need to try to cut calories; Mattson's research suggests you'll naturally consume less that day. Or try fasting one day a week. Just drink plenty of water.

    Rigor that is not, but the basic ideas are there: less food, maintain the right nutrition, and reap the benefits. The evidence to date suggests that at least some of the benefits scale with the reduction in calories: mild CR brings mild benefits; resistance to age-related disease, and possibly a meaningful extension of maximum human life span.

    The spread of knowledge regarding calorie restriction is nothing short of an impressive success for the healthy life extension community. It shows just what can be done when advocacy and small, active interest groups intersect with the scientific community in a synergy that pushes both sides forward. Funding is hard to find without interest, knowledge and support; it's hard to raise support and educate the world without new science to back you up. But folk have managed to bootstrap calorie restriction research and public knowledge of the practice of calorie restriction into a growing, self-sustaining process.

    Well done.

    The take-away lesson here: this shows that we can do exactly the same - and better - for any aspect of scientific anti-aging research we set our minds to. It's not rocket science, and we have a lot of lives to save - so the faster we get this bus moving, the better!

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    Longevity Requires a Cancer Cure

    Via the Guardian, a brief but pointed look at cancer statistics: "The number of cases will go up because there will be more people and cancer patients will live longer, but the chance of contracting cancer will largely stay the same. Currently around one in three people in Britain will be diagnosed with cancer at some point during their lives. Prof Moller's predictions showed that the number of annual cases of cancer in men will go from 111,639 in 2001 to 152,381 in 2020, a rise of 36%." All our work to extend healthy longevity will be for naught without highly effective, widely available, low-cost therapies for cancer. Your chances of developing cancer become ever-greater with each passing year. Fortunately, this is one area in which the funding, public support, patient advocacy and research infrastructure is already in place; those of us who can afford to wait 20 years for a cure should be cautiously optimistic.

    Link: http://www.guardian.co.uk/uklatest/story/0,,-6138202,00.html

    On Embryonic Stem Cell Research

    From the Journal of Cell Biology: "Talk of policy has dominated talk of science for those interested in embryonic stem cell science. But research is continuing, and the advances are making clear why embryonic stem cells [ESCs] are such an important scientific and medical resource. ... To assess the state of the field, we check in with five bench scientists who are pushing embryonic cells to be all that they can be. The projects they are tackling include a survey of what gives an ESC its identity, new attempts at deriving ESCs from [somatic cell nuclear transfer, or therapeutic cloning], perfecting the transformation of ESCs into either oligodendrocytes that make myelin or pancreatic cells that make insulin, and creating an ESC-based model for Alzheimer's disease." ESC research is vital to the end goal of replacing cells lost with age, thus preventing a range of degenerative, fatal conditions.

    Link: http://www.jcb.org/cgi/content/full/174/6/743

    The Cost of Medical Socialism

    Medical socialism is the situation in which public funds - taxed dollars, other government money - are used to pay medical costs. It is the end state of increasing regulation, in which politicians - having generated regulatory laws over the years that, whatever the original intent, ensure poor service, high prices and misery - answer cries for change by greatly expanding government control over the provision of medical services. The spiral down continues from there. You'd almost think that most people have already forgotten what happened to the Soviet Union and those forced to live their lives in that prison, the ugly final resting place of a centrally controlled culture.

    In a free market, unmolested by regulation, the provision of services is subject to competition - and the review and quality assessment of services is also subject to competition. Poor service providers and poor reviewers fail quickly. You, as the buyer, have the ultimate power: choice. In a socialist system, you have no power, because you have no choice. Poor provision of services spreads and prospers at your expense.

    In a free market, participants can adjust their investment, production and efficiency at every level through the essential feedback mechanism of price. This allows bad investments to be ruthlessly rooted out, maximizing progress and choice. In a socialist system, price signals are so distorted that bad investments grow. Political patronage rewards the few at the cost of the many; slow progress and bad goods are the norm. Worse, there is no way to assign scarce goods - and the investment necessary to make more of them - through the mechanism of pricing. The result is shortages of essentials, gluts of the useless, and rationing.

    There is no free lunch. The resources for your medical services must come from somewhere; someone must pay the price. You do not live in a truly free market. Remember that.

    But back to the choice. In the European socialist systems today, the most glaring costs are rationing and the absence of choice - and the suffering and death that results. Under what system would you rather live when you fall seriously ill? The one in which faceless bureaucrats decide you are not cost effective, or the one in which you had the opportunity to have saved money or buy simple insurance, giving you the power to make your own medical decisions in a market of competitors eager to give you good value?

    Alzheimer's drug ruling 'a kick in the teeth for sufferers'

    Nice chief executive Andrew Dillon said: "Alzheimer's is a cruel and devastating illness and we realise that today's announcement will be disappointing to people with Alzheimer's and those who treat and care for them.

    "But we have to be honest and say that, based on all the evidence, including data presented by the drug companies themselves, our experts have concluded that these drugs do not make enough of a difference for us to recommend their use for treating all stages of Alzheimer's disease.

    "We have recommended the use of these drugs where they have the potential to make a real difference, which is at the moderate stage of the illness."

    ...

    Professor Roy Jones, director of the Research Institute for the Care of Elderly at St Martin's Hospital, Bath, said: "I am going to be put in the unethical and difficult position of saying, 'I'm sorry, you must come back when you are worse'."

    Think about this. What does it say about the society in which you live: that the most basic choices in treatment for serious, life-threatening age-related disease are made for you by someone who cares nothing for your welfare, will never meet you, and whose decisions you cannot influence. There is a better way, you know.

    Rheumatoid arthritis patients face unofficial postcode lottery for treatment (PDF):

    Dr Kay, a consultant rheumatologist at the Freeman Hospital and Newcastle University, Newcastle upon Tyne, UK, said: “Nearly half of the consultants (46%) indicated that they had some form of limitation in their prescribing of anti-TNF agents for RA according to NICE guidance. Of these, 70% said these limitations were mainly in the form of capped funding or capped numbers of patients; staffing or lack of other facilities was a problem for 21% and 9% respectively.

    “The consultants said they faced problems such as a fixed number of patients that they were allowed to treat each month, fixed financial caps, bans on treating any more patients until the next financial year, and the fact that different primary care trusts had different financial limits. Waiting lists were also a means of controlling access to treatment, with some patients waiting as long as 156 weeks.”

    The nationalized health services of Europe are a more obvious socialism than what is presently happening in the US, via encroachment of schemes like Medicare and what is misleadingly called "health insurance" (more accurately viewed as highly regulated, inefficient health plans). The end result is the same: a web of regulation and socialized costs that chokes the marketplace, distorts price signals, reduces quality and rations availability. And once you choke the commercial side of medicine, you have choked investment in research; investors will depart - and have been, and are, departing - for greener fields in other industries.

    This is not the world to be living in when our future is so dependant on advances and competition in research and development of medical technology. So what are we going to do about it?

    If We Fail, It Will Be From Ignorance:

    Economic ignorance, willful or otherwise, is the death of cultures. The systematic destruction of incentives for progress - engineered by those who do not care to realize they are pulling the house down around their ears - will be the death of you and I as well if it continues. If we permit the ignorant to rule over medicine and medical research, destroying it in the process, then we deserve our fate

    ...

    Why put your life and health into the hands of people who have no interest in helping you? Why think that socialism in medicine will work this time, when it has failed miserably everywhere else? As time moves on, those of us reading this now will become increasingly reliant on the new medical technologies of healthy life extension for health and longevity. If the future of medicine is socialist, then we won't be seeing much of that future - the destruction socialism and centralized, regulated systems bring to research and progress will see to that.

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    Speculating On Fat and Dementia

    From MSNBC, news of another study suggesting that "a heavier weight in middle age may mean a higher risk of dementia later in life. ... It's possible [that] excess fat cells have some direct effect on brain function. For example, some studies suggest the 'hunger' hormone leptin, which is produced by fat cells, plays a role in learning and memory. And although these study participants were in generally good health, disorders like elevated blood pressure and diabetes could act as a bridge between high BMI and poorer cognitive function. Thickening and hardening of the blood vessels supplying the brain can contribute to dementia ... Similarly, diabetes may harm cognition by either leading to artery disease or via direct effects of the hormone insulin on brain cells."

    Link: http://www.msnbc.msn.com/id/15206566/

    The Damage Done By Patents

    A patent is, in essence, a way to use government force to expand your short-term profits at the expense of everyone else. From this piece at The Scientist: "A narrowing or invalidation of the patents could speed up research, many scientists say. Some researchers complain that the licensing process slows their work down, while others say it is prohibitively expensive. ... It slows things down and sort of sets up an artificial step in the process." A patent is a form of regulation, and regulated industries mean slow progress, expensive goods, and an reduction in competition. Competition is the only incentive process that leads to better, cheaper, more effective products. Industries that depend absolutely on ideas but are largely free of patents - or even copyright in the case of fashion design - are highly dynamic, competitive and profitable. Why, then, do we put up with this nonsense of the few exploiting the many in far more vital industries such as medicine?

    Link: http://www.the-scientist.com/news/home/25037/

    Dying to Live Forever

    Greg McMullen dropped me a line to let me know that his thesis is available online (in PDF format); an examination of the pro-radical life extension community.

    The idea that bio- and nanotechnologies could drastically extend human lifespans is gaining currency, both among supporters and opponents of the potential technologies. Loosely organized immortalist groups are under political fire from all sides, faced with opposition from well-organized conservative, religious and environmentalist groups. If they do not find political allies soon, immortalists may find that the technologies they have such high hopes for are banned before their potential can be realized.

    This thesis explores the culture of those who believe that human lifespans should be open-ended and propose technological interventions to keep us youthful and prevent "involuntary death." A study of mythological and fictional tales of immortality lays the groundwork for an examination of immortalist discourse. Through Serge Moscovici's theory of social representations and Norman Fairclough's critical discourse analysis, the beliefs and attitudes of immortalists are explored and suggestions are made for improving engagement with potential political allies.

    It's very interesting and readable - don't let the first half of that last sentence above fool you. As a part of looking at the healthy life extension community, for example, it contains an examination of the Immortality Institute folk and an interview with biomedical gerontologist Aubrey de Grey.

    Beyond that, the thesis touches on many of the issues I've briefly explored in this blog over the past couple of years, as well as a topic that I don't tend to look at all that much in this forum: the relationship between technological development and mythology. We are, if nothing else, creatures of myth; our constant chatter and communication of a thousand different forms and voices produces resonances. These resonances are stories and story forms of varying strength (pervasiveness, geographical or cultural extent, frequency of retelling, level of variation) that we find attractive for consistent, basic reasons relating to the human condition; our physiology; the hardwired desires we've inherited as primates; the way in which we form societies and relationships; certain consistent patterns within those societies and relationships. The Hero's Journey (the Monomyth) is one such resonance, but there are many others; long, short, old, new, widespread, or limited in extent.

    Given a technology that allows us to do something new, we will turn that capacity to build our world a little closer to the world of myth that makes us comfortable. In the process, some feedback or change to the human condition slowly - very slowly - introduces changes into our mythic structure.

    Myth drives the application of technological capabilities, which then in turn change the myth - but in the short term, myth is in the driving seat, all other things being equal. For our near-term future, the myths of longevity and immortality - and the myths used to make us feel better about lacking both - are important considerations when it comes to raising support for research to greatly extend the healthy human life span. From the thesis:

    The common thread running through our earliest mythological tales of immortality is that death, while not necessarily desirable, is unavoidable and a fundamental part of being human. In spite of his best efforts, Gilgamesh could not achieve immortality. Given a choice, Tithonus likely would have chosen death over eternal decrepitude. While there is no suggestion in these stories that death gives value to life, they both certainly leave the impression that we should grow accustomed to the idea of dying, because there can be no desirable alternatives to it.

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    Mole-Rats, Thyroid Hormones

    Yet more naked mole-rats in this research on thyroid hormone levels and longevity in rodents, via EurekAlert! This one raises more more questions than it answers: "The thyroid gland produces thyroxine (T4) which converts to triiodothyronine (T3) in the presence of iodine. T3 is the active component of T4 and is the key hormone in regulating metabolism ... T4 levels varied significantly between all of the groups, with the shorter-lived groups having higher levels of T4 than longer-lived groups. The mice, for example, had twice as much T4 as the Damara mole-rats and had and three times more than that of the naked mole-rats ... There was also a significant difference in T3 levels between the naked mole-rats and the guinea pigs." To put this in an interesting context, it has been shown that calorie restriction lowers levels of T3. A complicated thing, metabolism. This is why I support efforts to identify and fix cellular damage (easier, more effective) rather than tinkering with metabolic processes (harder, less effective).

    Link: http://www.eurekalert.org/pub_releases/2006-10/aps-lrh100706.php

    Destroying Chronic Infections

    One main reason your immune system fails with age appears to be that chronic infections by the likes of cytomegalovirus (CMV) cause too many of your immune cells to be - uselessly - specialized. As noted in the New Scientist, researchers are looking into a possible way of clearing these infections from the body: they "studied an acute and chronic meningitis infection in mice, called lymphocytic choriomeningitis virus (LCMV). They discovered that mice with chronic infections had high levels of the inflammatory-damping chemical interleukin-10 (IL-10). When they gave mice with chronic LCMV a drug that blocks the inflammatory-calming action of IL-10, the inflammatory immune response was re-activated. Within a week the mice were healthier. In two weeks, they had cleared the virus completely." Now if this could be turned against CMV early in life, the immune system would look a lot better later on - but a method of cleaning out the uselessly specialized cells would be needed to help those suffering now.

    Link: http://www.newscientist.com/article/dn10264-inflammation-turned-on-to-fight-killer-viruses.html

    Thoughts on What Will Be Well Funded First

    Randall Parker uses a recent advance in the quest to apply stem cells to regenerate baldness as a springboard for thoughts on where the funding goes first these days:

    I am convinced that rejuvenation therapies that improve outward appearances will hit the market much more rapidly than therapies that make inner organs young again. There are at least four reasons for that. First and most obviously, the skin and hair follicles are easier to reach. Second, people care (however unwisely) more about their outsides than the age of their livers or kidneys. They want to look young and that desire is pretty intense. Third, at least in the United States plastic surgery therapies do not appear to be as tightly regulated as most therapies. Fourth, people spend their own money on plastic surgery and other appearance enhancing therapies. Conservative insurance company rules for which therapies are legitimate do not hold back the introduction of new therapies.

    My, it's almost as though less regulated markets have faster rates of progress and more rapid competitive introduction of new technologies. Funny that - or at least it would be funny if all the regulation that does exist today wasn't leading to an unending series of deaths; people dying because politicians and a thousand greedy parasites have their hooks into the engine of medical development, slowing the development of therapies in the name of their own short-term advantage.

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    Rate of Living Theory Still Dead

    Last nails from EurekAlert!: "One early theory, the rate of living theory, held that every organism has a set amount of energy to expend. Once the animal expended that number of calories, the grim reaper was on the doorstep. Over the years, the theory has become much more sophisticated, but metabolic rate and aging have remained linked ... Runner mice that had access to a wheel expended 25% more energy over the course of their lives compared to both the runner group that did not have a wheel and the regular mice ... The rate of living theory would have predicted that the running group that expended more energy would die earlier than the two groups that did not ... This was not the case. There was no difference in life span between the two runner groups, even though one expended more energy." Recall that exercise is demonstrably good for health and resistance to age-related disease.

    Link: http://www.eurekalert.org/pub_releases/2006-10/aps-ed100206.php

    Naked Mole-Rats Again

    More on long-lived naked mole-rats and their ability to shrug off oxidative stress via Newsise: "The researchers next looked at how much damage the oxidation had caused. It is possible, they reasoned, that the mole-rat suffers greater oxidative stress, but its physiology had somehow prevented damage from occurring. The researchers measured oxidative damage in lipids, DNA and proteins and found that naked mole-rats showed much greater levels of damage to each of these biological molecules, in all tissues assayed, when compared to mice. ... All of the classical measures of oxidative stress are higher in the mole-rat. Given that naked mole-rats live an order of magnitude longer than predicted based on their body size, our findings strongly suggest that mechanisms other than attenuated oxidative stress may explain the impressive longevity of this species." A puzzle, and one we humans should be interested in the answer to: oxidative stress causes us serious damage and is one root cause of aging. How are the mole-rats getting away with it?

    Link: http://www.newswise.com/articles/view/524122/

    "Use It Or Lose It" Demonstrated

    Data noted by the LEF News provides a practical demonstration of "use it or lose it" for the retired set. "You'd think that retiring would make you healthier. Finally, you can leave all the stress of the working world behind. Think again. Complete retirement leads to an 11 percent decline in mental health, an 8 percent increase in illness, and a 23 percent increase in difficulty performing daily activities over a six-year period ... The declines in health are much lower and, in some cases, nonexistent for those that continue to work part time. ... Working longer is not always the path to better health, of course. If your work is routine and stressful or not intellectually challenging, then working longer can actually hurt your health. [The objective] should be to find a job that keeps you meeting fulfilling goals. ... There seem to be health benefits to keeping all of your body parts moving including the nerve cells in your brain."

    Link: http://www.lef.org/news/LefDailyNews.htm?NewsID=4417

    The Optimistic View

    Progress in science will - sooner or later - become progress in the medical technology you can buy. From the Daily Telegraph: "new drugs and vaccines will soon emerge to tackle a range of cancers, while stem cells will help cure diseases such as diabetes, Parkinson's and multiple sclerosis. Miniature technology and smart materials are also predicted to play a greater role in medicine, helping to repair damaged nerves and possibly broken spinal cords. ... Some of the breakthroughs, such as gene profiling to detect disease risk, are predicted to become available within a decade. Others, such as growing new organs through stem cell research, may take longer but are still likely in the foreseeable future. ... We see ways of helping people with disabilities such as spinal injuries, nerve repair, bionic eyes, bionic ears, bionic bladders and so on. The whole field of materials connecting with the body is one of the most important areas of medical research for the future."

    Link: http://www.news.com.au/dailytelegraph/story/0,22049,20546198-5006007,00.html

    How Age-Damaged Mitochondria Cause Your Cells To Age-Damage You

    Free radicals, and reactive oxygen species (ROS) in particular, play an important part in aging. These are (usually small) molecules lacking an electron needed for stability; they will steal an electron from the first thing they bump into. Like pulling a cog out from clockwork, stealing an electron from a protein or enzyme is usually not good for the finely-tuned biochemical machinery of our cells. The free radical might be rendered safe in the process, but it has left some form of chaos and damage in its wake.

    Free radicals are sufficiently dangerous to biochemical machinery that some of our body's defenders use bursts of free radicals as a kill mechanism.

    Scientists generally concur that accumulated damage throughout the body due to free radicals is one important root cause of age-related degeneration - but the devil is in the details. The vast, overwhelming majority of those free radicals are generated by your own metabolism as an unavoidable byproduct. The rate of free radical generation increases greatly with age as the basic mechanisms of your of metabolism are themselves damaged by the free radicals they created. This is not a one-step process, however. I'll try to walk through it at a high level, cribbing from the mitochondrial free radical theory of aging proposed by Aubrey de Grey and working its way into general acceptance.

    • Within each of your cells are many mitochondria, tiny biochemical power plants that convert chemicals from food to ATP, the basic fuel molecule used by your cells to provide energy for life.

    • Mitochondria were once a separate organism that came to live in symbiosis with ancestral cells. As such, they brought their own DNA to the party; some of it still remains within our mitochondria, separate from the DNA we carry in chromosomes in the cell nucleus.

    • Mitochondria have a couple of ways of generating ATP. The more efficient of these methods - oxidative phosphorylation (OXPHOS) - generates some amount of free radicals as a natural byproduct, and requires the proteins coded in the mitochondrial DNA to function. It is the predominant way by which healthy cells generate their power.

    • Free radicals created through OXPHOS within a mitochondrion are most likely to damage that mitochondrion; they're very reactive, so they won't get far before sabotaging something. The components that really matter are (a) a membrane that helps organize the movement of various chemicals in the process of generating ATP, and (b) the mitochondrial DNA.

    • Sufficient free radical damage to mitochondrial DNA shuts down OXPHOS within that mitochondrion, as the necessary proteins can no longer be produced. The mitochondrion switches over to using a less efficient method of producing power, one that doesn't produce free radicals, but has to run at a much higher rate to produce the same level of ATP.

    • Mitochondria, like most cellular components, are recycled on a regular basis. Components called lysosomes are directed around the cell in response to various signals, engulfing and breaking down damaged or worn components. After the herd has been culled, surviving mitochondria within a cell divide and replicate, much like bacteria, to make up the numbers.

    • The signal to break down a mitochondrion is triggered by sufficient damage to its membrane: a sign that it's old, leaky, inefficient and needs to be replaced with a shiny new power plant.

    • BUT: if a mitochondrion has had its DNA damaged to the point of stopping OXPHOS, it will no longer be producing free radicals that can damage its membrane. So it will never get broken down by a lysosome. When the time comes to divide and replicate, it will replicate its damaged DNA into new mitochondria. None of those new mitochondria will be producing free radicals via OXPHOS, and so will not be recycled either.

    • One DNA-damaged, non-OXPHOS mitochondrion will eventually take over the entire mitochondrial population of a cell in this way. At that point, the trouble really gets started.

    • By the time you hit late life, perhaps 1% of your cells are in this state of being taken over by non-OXPHOS mitochondria. As for any neighborhood or city, it only takes a small proportion of dangerous criminals to make life really unpleasant for the rest of us.

    • Non-OXPHOS mitochondria have the unfortunate effect of depleting a needed molecule used in many cellular processes, NAD+. This is a carrier molecule in the OXPHOS process, given an electron (and turned into NADH in the process) to port between point A and point B within the mitochondria. Once the electron is delivered, the NADH becomes NAD+ again. But without a working OXPHOS process to return NAD+ into circulation, the cell would quickly build up a deadly excess of NADH, run out of NAD+ and die.

    • Fortunately for the cell, and unfortunately for us, there is another way to recycle NADH into NAD+. Since NADH is just NAD+ with [amongst other things] an electron stuck to it, all the cell has to do is export those unwanted electrons.

      Editing for clarity on 11/22/2009: In the bullet points above, I omitted details of the reaction that transforms NAD+ to NADH in order to focus on the electron that is ported around. Wikipedia gives an introduction to the full picture, which also involves an extra hydrogen atom - NADH is NAD+ with the addition of a hydrogen atom (one proton, one electron), and an additional electron. Nonetheless, it is the shuttling and exchange of electrons that is important here.

    • In a form of chemical waste dumping, this is just what the cell does. Structures on the cell membrane known as the plasma membrane redox system (PMRS) export electrons from NADH, recycling it into NAD+. This process is only very active in cells which have been taken over by DNA-damaged, non-OXPHOS mitochondria, but their outer surfaces are little hotspots of electron dumping.

    What do these electrons do? Well, for one, they combine with oxygen molecules - which are abundant in any of our living tissue - to create reactive oxygen species (ROS): more free radicals. So you have the Rube Goldberg system outlined above whereby a few free radicals have caused a cell to become an ongoing, major exporter of free radicals into the surrounding environment. These will make life unpleasant for surrounding cells, but that is most likely not the real problem. ROS just can't travel far enough to explain how a corrupt 1% of our cells can cause a large fraction of the difference between being young and being old.

    A more likely target for all the newly created ROS is cholesterol. Cholesterols, such as low-density lipoproteins (LDL) are used everywhere in the body and travel widely. If ROS reacts with nearby LDL - and there will always be nearby LDL - to form damaged, oxidized cholesterol, that damaged cholesterol can then be incorporated into and further damage biochemical processes throughout the body. For example, its effects on our arteries is well known:

    In conditions with elevated concentrations of oxidized LDL particles, especially small LDL particles, cholesterol promotes atheroma formation in the walls of arteries, a condition known as atherosclerosis, which is the principal cause of coronary heart disease and other forms of cardiovascular disease.

    There are many other ways in which accumulations of oxized cholesterol can send biochemical processes awry. This, then, seems to be a good candidate for the plausible, systematic method by which a small number of cells can work such varied damage upon your entire body.

    Aubrey de Grey has proposed an engineering solution to this problem, based upon this way of looking at it. That is to go straight to the root, and get the OXPHOS process working again by (a) moving mitochondrial DNA into the nucleus, and (b) ensuring that the necessary proteins can make it from the nucleus back into the mitochondria where they are needed.

    As usual, we're lucky - evolution has done the hardest part of this for us already. Mitochondria are very complex -- there are about 1000 different proteins in them, each encoded by a different gene. But nearly all of those genes are not in the mitochondrion's DNA at all! -- they are in the nucleus. The proteins are constructed in the cell, outside the mitochondrion, just like all non-mitochondrial proteins. Then, a complicated apparatus called the TIM/TOM complex (no kidding...) hauls the proteins into the mitochondrion, through the membranes that make its surface. Only 13 of the mitochondrion's component proteins are encoded by its own DNA.

    This gives us a wonderful opportunity: rather than fixing mitochondrial mutations, we can obviate them. We can make copies of those 13 genes, modified in fairly obvious ways so that the TIM/TOM machinery will work on them, and put these copies into the chromosomes in the nucleus. Then, if and when the mitochondrial DNA gets mutated so that one or more of the 13 proteins are no longer being synthesised inside the mitochondria, it won't matter -- the mitochondria will be getting the same proteins from outside. Since genes in our chromosomes are very, very much better protected from mutations than the mitochondrial DNA is, we can rely on the chromosomal copies carrying on working in very nearly all our cells for much longer than a currently normal lifetime.

    A great deal of work is needed to make this happen, even with today's biotechnology. But if you don't get started, you'll certainly never finish! Generous donations to the Methuselah Foundation help to fund the first steps in this direction.

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    The Ageism That Colors Views of Death

    Anne C. reinforces a good point she has made in the past (and which can't be made too often, at least until the point is gone):

    I've never understood people who say things like, "Well, I want to live to be 100 in perfect health, and then die peacefully in my sleep". The contradiction in that sort of statement should be obvious. Healthy people don't die in their sleep, "peacefully" or otherwise. You don't hear about too many 25-year-olds dying suddenly of heart attacks or strokes during their nightly slumber. There are a few -- some people end up expiring suddenly in their twenties or thirties due to undiagnosed cardiovascular dysfunction and other similar conditions, but the majority of people found dead in their beds are elderly.

    When people in their twenties die, it's usually considered tragic. When babies are found dead in their cribs, it's referred to by a name ("Sudden Infant Death Syndrome"). But when elderly people die, in bed or otherwise, there tends to be a curious tone of, "Well, at least they went peacefully".

    Is this attitude a result of resignation to what most folk - falsely - believe to be inevitable and writ in stone? Is it a construct built atop the green-eyed monster of envy; that a person who led a full life has had their turn, had enough, doesn't deserve more? Or is it built upon fear of the age-related degeneration that most people believe - falsely - must come to pass for them as well, and a desire to avoid encountering any reminder of that fate? Whatever the roots, we can do better than this. Our situation is the archetypical morality play; the more rapidly and effectively we develop real anti-aging medicines to help those suffering the effects of aging today, the more health and life we will received in turn.

    The aged and frail are neither strangers nor aliens. They are people too, just like you and I; if they lived in the body of a 30-year old, you'd treat them just the same way as any other middle-aged person and be none the wiser. In many cases, they've used their extra years of life to become better folk than you or I, for any value system you care to name.

    An extra year of health and life is an extra year of health and life, no matter who it comes to. Any technology capable of giving that year to one person can give it to many; we're all customers in this market. Ageism, like racism, is one of those states of mind that will come to be seen as crude, undesirable and uncultured - and we will look back and shudder at the ugly actions and inhumanities that were commonplace during its era of prevalence.

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    Controlling Mis-Inflammation

    Chronic inflammation is very bad for your long term health and longevity: it's a potent source of cellular damage. Scientists are working hard to find ever more sophisticated ways to turn off inflammation, as illustrated in this article from EurekAlert!: "researchers identified a biochemical signaling pathway between human blood platelets, cells essential for blood clotting, and monocytes, white blood cells the body makes to fight inflammation and infection ... the blood platelet signals the monocyte two times, triggering production of Cox-2, an enzyme that helps regulate inflammation. But when blood platelets and monocytes get their signals crossed, it can lead to overproduction of the enzyme and result in cardiovascular diseases that strike and kill millions of people worldwide. ... This discovery has immediate clinical relevance. This opens the potential of developing medications for both the prevention of long-term atherosclerosis (clogged arteries) and the acute events of heart attack."

    Link: http://www.eurekalert.org/pub_releases/2006-10/uouh-bcl100506.php

    On Medical Research Funding

    Thoughts from Ronald Bailey at Reason Online on levels of funding for medical research: "The felt scarcity of research dollars probably results from two interacting developments. First, as biomedical knowledge increases exponentially the possible number of worthwhile experiments that researchers can imagine also soars. This leads to ever more proposals being submitted for funding consideration. Second, the questions being asked by researchers are now more complex, making biomedical experiments more expensive. Perhaps less benignly, overcautious regulatory requirements are eating up a lot of clinical pharmaceutical research dollars and slowing the introduction of new medicines. ... All I know is that the proper amount of research spending is that amount that will enable me and you to live as long we'd like. Is that asking for too much?" Remember that not all research funding is equally effective: it's the incentives that matter more than the dollar amount when it comes to results accomplished.

    Link: http://www.reason.com/rb/rb100606.shtml

    Aubrey de Grey Video at TEDTalks

    The TED Blog notes that video of biomedical gerontologist Aubrey de Grey from 2005 is now available on the TEDTalks section of their website.

    Aubrey de Grey, British biogerontologist and founder of [the Strategies for Engineered Negligible Senescence, or SENS], controversially claims to have created a roadmap to defeat biological aging. In this talk, he argues that aging - like other diseases - can be cured, and that humans can live for centuries, if only we approach the aging process as "an engineering problem."

    Better late than never; you folk engaged in reformatting and transporting this sort of thing to the video sites of the world might not have caught this one yet. Much more video footage of Aubrey de Grey - including interviews, explanations of SENS and related science, the Methuselah Foundation and the moral imperative we all have to do something about the terrible toll of aging - can be found at the following locations:

    Send the links to a friend today - the more people exposed to these ideas, the better. Widespread discussion and education is progress towards the growth of an influential pro-healthy life extension community. Such a community is a necessary step on the path to large-scale research and scientific infrastructure dedicated to the development of real anti-aging medicine.

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    Practical Regenerative Medicine

    Via Science, a look at the near future of regenerative medicine from the perspective of the newly minted researchers who will be making it all happen: "Stem cells are used in many different types of research: uncovering basic developmental mechanisms, exploring mechanisms of cell proliferation, and trying to develop cell transplantations and drug screening platforms ... Tissue engineering is a fairly underutilized area. Instead of growing cells for transplanting, you could take the cells and entice them to grow over scaffolds into a structure or organ in vitro and then transplant organs and tissues rather than cells into patients ... stem cell research - in the long term - can completely change our possibilities to repair the brain and do something for many neurological patients where we have nothing today."

    Link: http://sciencecareers.sciencemag.org/career_development/previous_issues/articles/2006_10_06/careers_in_stem_cell_research_rejuvenating_biology_and_medicine

    Longevity Mutations and Cancer

    Nature summarizes recent research into longevity mutations and cancer in nematode worms; the results suggest that further investigation of insulin pathway mutations in mammals could prove profitable. "Mutations in the [nematode] C. elegans insulin-receptor gene daf-2 extend lifespan by more than twofold. By contrast, mutations in the gld-1 tumour-suppressor gene cause germ cells to re-enter mitosis, overproliferate and give rise to tumours that kill the animal. When the authors combined the two mutations, however, the lifespan was indistinguishable from that of the daf-2 single mutant - the tumorigenic effect of gld-1 was completely abolished. How might the lack of insulin signalling prevent tumour development? The authors found that cell division decreased and apoptosis increased in the germ lines of the [daf-2 plus gld-1] double mutant compared with the gld-1 single mutant. Interestingly, daf-2 mutations affected only germline mitosis in the tumour, and not in the normal germ lines of otherwise wild-type individuals." Tantalizing hints that there might be a way around the "cancer or aging, pick one" situation.

    Link: http://www.nature.com/nrg/journal/v7/n10/full/nrg1972.html

    100,000 Tragic Reminders, Each and Every Day

    There is a point to this exercise: this post; the other posts on Fight Aging!; the Longevity Meme; the Methuselah Foundation; the Strategies for Engineered Negligible Senescence (SENS); the activism; the wider conversation and advocacy for healthy life extension. Every day, more than 100,000 people die from the results of accumulated age-related damage in their tissues: each one is a pointed, grim reminder that we could be doing far more than we are to make it possible to repair that damage.

    On some days, we know one of these people - and then we grieve for a while, before trying to put it out of our heads again. A father; a mother; a sister. It has to stop: one day, if we don't get our act together pretty damn quickly, one of those pointed, grim reminders is going to be you - and the years leading up to that event will not be free from suffering. The end of life - the slow failure of your biology under the weight of damage we almost know how to repair - is not a pretty picture.

    This future is not inevitable! Scientists know more than enough to make a start on the defeat of aging; more than enough to make significant progress on real, working anti-aging medicine within our lifetime. But this progress requires your support and understanding - all our support. Medical science does not move forward in a vacuum, but rather only when we all step forward to call for results, putting our money where our mouths are.

    Where would you rather be in the decades ahead? Suffering and dying, or out there in world with vigor and health, learning and enjoying life? If you want the better of those options, you'll have to help the rest of us invest in making it a reality.

    Give it some thought. The future is what you make of it.

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    CIRM and Timelines

    The draft strategic plan (PDF) developed by the California Institute for Regenerative Medicine (CIRM) provides another confirmation of the conventional wisdom regarding timelines for the next generation of stem cell therapies. From SignOnSanDiego.com: "The proposed strategic plan includes five and ten year goals, and a breakdown of the money that will be spent on a multitude of research areas. Since bringing a new product to market can take up to a dozen years and $1 billion - not to mention the millions of dollars that can be spent only to have a drug fail - the committee said it does not expect to be able to fully fund a stem cell therapy and bring it to market. But it does expect to help fund some early-stage clinical trials to establish proof of concept of new therapies using animal models, and some small, safety trials in humans." Medical research and development will never be as fast as we would all like it to be, even outside the realm of wasteful government spending; this sort of timeline is much as expected.

    Link: http://www.signonsandiego.com/news/business/biotech/20061004-9999-bn05stems.html

    Supercentenarian Research Foundation

    An update on progress in forming the Supercentenarian Research Foundation (SRF) can be found in the Pittsburgh Business Journal: "The foundation's goals are two-fold: to help improve quality of life for aging individuals and to try to emulate their successful longevity. The foundation will provide funding for research designed to identify the most important factors in helping supercentenarians avoid getting common diseases that kill most people at a younger age. ... Those who are approaching the maximum lifespan can provide us with some important information about aging. Why are they able to live longer than everybody else? Why don't they live longer than they do? The funds for research will help answer these questions." The SRF is an outgrowth of the Gerontology Research Group community; it's always good to see people setting forth to make a difference.

    Link: http://pittsburgh.bizjournals.com/pittsburgh/stories/2006/10/02/daily31.html?t=printable

    More Surveying of Attitudes to Healthy Life Extension

    I view surveys of attitudes to healthy life extension as another part of the greater conversation on engineering longevity. This multithreaded conversation, ever branching and merging, wends its way through conversations, scientific publications, the mainstream media, blogs, magazines and a hundred other ways in which we talk to one another. The more we see that conversation grow, the more progress must be taking place.

    This is what I tell myself, at least, when I see scientific studies on attitudes to healthy life extension - as opposed to, say, scientific research dedicated to making healthy life extension happen in the first place. There are folk in the world who would rather talk amidst flames and falling timbers than run for the fire hose; more power to them, but I'd rather see the resources going elsewhere.

    Here's an article on the study in question:

    Some participants in the study said they would like to significantly extend their lives, while a few stated that they would like to “live indefinitely”. But the project Research Manager Dr Mair Underwood said not everyone interviewed for the project shared these views.

    “It cannot be assumed that all people would welcome life extension,” she said.

    “Some people definitely do not want to extend their lives as they feel it is ‘greedy', ‘selfish' or ‘messing with nature'.

    ...

    “But for many of those we asked the answer is a very qualified `yes`. While the idea appealed to them they felt there were a lot of other factors to consider before they said yes to life extension.”

    Dr Underwood said the most important consideration was quality of life as participants did not want to spend their extra years in a nursing home.

    Much as we'd expect at the high level, given past experience of less scientific surveys; it will be interesting to see the results in detail. Again, another ringing endorsement of a focus upon dispelling the Tithonus Error when raising support for healthy life extension research. People want to know that they are not going to be frail for longer, but rather youthful for longer.

    One wonders if all the nonsense philosophy and navel-gazing bioethics floating around the healthy life extension community and the pro-death opposition is just so much smoke in the smokescreen. What average folk - those not paid to think deep thoughts and throw spanners in front of the real workers - care about are the by-products of youth and health: self-suffiency, the absence of suffering, a life of vigor and function. Which leads us to suppose that perhaps the Tithonus Error - the mistaken, often knee-jerk belief that a lengthening of life would mean more and greater disability - really is the main roadblock to greater widespread support for healthy life extension research. ... Abolish the vision of Tithonus in the minds of the many, and the road to the future of healthy life extension will open wide? Food for thought.

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    Speeding the Biotech Revolution

    (From the Northwest Florida Daily News). The latest X Prize to be announced is indeed to speed already rapid progress in the field of genomics, the basis for the advanced, personalized medicine of tomorrow: the X Prize Foundation "is now teaming with a wealthy Canadian geologist to offer $10 million to any team that can completely decode the genes of 100 people in 10 days. ... The $10 million purse is being put up by Stewart Blusson, a Canadian geologist involved in discovering a trove of diamonds south of the Arctic Circle in 1991." Like the cost of processing power for the computing industry, the cost of DNA sequencing is a marker for broad progress in the biotechnology revolution: the cheaper it becomes, the more can be done to advance medicine, health and longevity. The path to radical life extension requires a continued acceleration of this progress - the more research prizes, the better!

    Link: http://www.nwfdailynews.com/articleArchive/oct2006/geneticstudyunusualcontest.php

    Towards Early Alzheimer's Diagnosis

    If it is the case that Alzheimer's is a form of diabetes, sensible lifestyle choices could have a large effect in the earliest stages of the condition - as they do for diabetes. There is no present method for detecting the earliest onset of Alzheimer's, however - but scientists are working on it. From EurekAlert!: "an update on progress and new findings on his optical tests for the early detection of Alzheimer's disease ... Goldstein will present "proof of concept" evidence obtained in mice that the tests can detect early molecular signs of the disease in the eye even before Alzheimer's pathology is present in the brain. This achievement raises hopes for detecting the disease at its earliest stages and slowing the progression of the disease to a crawl. ... these techniques have been tested in a Phase I trial in humans with phase III multicenter human clinical trials slated for next year. In the end, the tests could cost less than $300 per test."

    Link: http://www.eurekalert.org/pub_releases/2006-10/osoa-otf100306.php

    Forthcoming SENS Book: Graphics Volunteers Sought

    From Michael Rae, Aubrey de Grey's research assistant:

    As some of you know, Aubrey and I have been working for some time on a popular book on SENS science. We are coming up on a publisher deadline, and most of our graphics volunteers have for various reasons bowed out. We really need some folks with the ability to put in some time on at least one (and of course preferably more) illustrations for the book in the next couple of weeks. Projects range from line drawings and graphs to actual illustrations.

    Please send email to the Methuselah Foundation if you can make such a volunteer contribution; it would be greatly appreciated, and acknowledged in the book.

    Time is of the essence, so step up if you have the talent! I'm looking forward to seeing the final draft; my few behind the scenes glimpses to date have been most promising.

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    More On CR, Aging In Monkeys

    The MIT Technology Review takes another look at the long-term study of calorie restriction and aging in rhesus monkeys. In short, they provide the same sort of preliminary data as human studies to date - but much more of it: "Although there is now strong evidence that caloric restriction prevents diabetes in the primates (the disease is a major killer of captive rhesus monkeys), it's still too early to assess the diet's effects on their lifespan ... The study will likely go on for at least another decade, since the monkeys are only now entering old age. ... preliminary evidence suggests that the diet is preventing loss of muscle mass, arthritis, menstrual irregularities, and other signs of aging ... Whatever the mechanisms turn out to be, [there's] something that happens with that extra reduction of food intake that really affects the aging process."

    Link: http://www.technologyreview.com/printer_friendly_article.aspx?id=17572

    Measuring Structural Skin Aging

    (From EurekAlert!) The biochemical processes of aging change the structure of skin, leading to the familiar visual signs - along with a host of other, far more serious issues in skin-like tissues throughout the body. Testing real, scientific solutions (not the useless junk pushed by the "anti-aging" marketplace) has been hampered up until now by a lack of good diagnostics: "Currently, dermatologists who want to check out the collagen network of a patient's dermis need to remove a sample of tissue and analyze it in the lab, under a microscope or by other methods. In particular, it is impossible to monitor variations in the very same spot as aging progresses. ... researchers [have] demonstrated a new technique that non-invasively measures in real time the level of damage to the skin from sun exposure and aging ... This new laser-based technique images the fabric of the deeper layers of the skin, combining methods for imaging collagen and elastin, whose degeneration causes the appearance of wrinkles and the progressive loss of skin smoothness."

    Link: http://www.eurekalert.org/pub_releases/2006-10/osoa-grd100306.php

    People Who Step Forward to Create the Future

    The future is created by people of determination, by their deliberate choice and action. Nothing else but human action will change the world; if we want the future to be a better place, then we must act. It is not sufficient to sit back and assume the matters you care about will be taken care of - because they won't be.

    I thought I'd point out an example of a fellow who is looking ahead in life, making the choice to help bring about the future he would like to see:

    I leave for Aruba tonight (overnight flight). By the time I come back I will be 21. That means I will never be denied the right to gamble or drink ever again because of age. It feels like an eternity has passed, and I’m just about to begin my poker career.

    I made a post a while ago saying that I was going to donate a small percent of my live tournament winnings to a charity. I have been criticized some at 2+2 for saying this and “not following through”, but I haven’t played a single live tournament since January. I assure you, I am a man of my word.

    ...

    I have researched many charities, and I knew that I wanted to sponsor a charity that will make a long term difference. Also, thanks to Ray Kurzweil and Aubrey de Grey (see my earlier blog about Kurzweil), I have some pretty radical views about the future, and I wanted to pick a charity in line with this.

    I did some research to see what causes Kurzweil endorses, and I found the Methuselah Foundation. Aubrey de Grey is the Chairman and Chief Science Officer, as well as a co-founder of the foundation. For those of you not familiar with the name, Methuselah was a man that supposedly lived to be 969 years old. The name is very appropriate, as the Methuselah foundation is trying to fight the aging process.

    ...

    I will be pledging 5% of whatever I win in Aruba (and this will continue for future tournaments I play as well) to SENS research. I would feel honored if other people were to read this post, and decide to do the same ... The potential of [the Methuselah Foundation] is too amazing to pass up.

    Many more people have made the choice to step up and take action - to invest in a future of far greater health and longevity for all by funding SENS research or the MPrize. We are fortunate to live in an era of rapidly advancing medicine and biotechnology. The journey to working therapies for aging is just beginning, but real progress is possible within our lifetimes - if we set to work and give our support to those at the cutting edge.

    Take a moment to think about what you want from the decades ahead. If health and vigor are on that list, then you will need to take action to ensure they are not stolen from you by the processes of aging.

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    Cell Wraps to Repair Blood Vessels

    The Boston Globe looks at a good example of present day research and development at the tissue engineering side of regenerative medicine. Pervasis Therapeutics is working to "fix arteries and veins not with tools, but by wrapping them in a gelatinous sheath of living, healthy cells. ... a 'cellular Band-aid' - a soft wrapper lined with a healthy colony of living blood-vessel cells. ... surprisingly, he found that they didn't need to be stuffed inside injured blood vessels to help them heal properly. Even wrapped around the outside of the artery, the cells appear to spur healing on the inner surface. In essence, the wrap fixes arteries by rebuilding them inside-out. ... If his idea works in humans, he said, it would show that you don't need to fully rebuild an organ to replace it. ... It could very well be that you could get 95 percent of the functionality that you wish, without getting anywhere close to 100 percent of the structure."

    Link: http://www.boston.com/business/healthcare/articles/2006/10/02/cells_not_tools_may_help_fix_arteries?mode=PF

    Telomeres and Osteoarthritis

    From ScienceDaily, news of a correlation between osteoarthritis and shortened telomeres: "X-rays of both hands were taken of all participants to check for signs of osteoarthritis and a blood sample was taken to assess 'biological aging' in white cell DNA. ... Unsurprisingly, the findings showed that white cell telomere lengths were associated with chronological age. The older a person was, the shorter they were. But among the 160 people with hand osteoarthritis, the telomere length was significantly shorter than among those without the disease ... the amount of telomere shortening was equivalent to that accrued over 11 years in healthy people ... The more severe the disease, the shorter was the telomere length. ... The authors suggest that both the aging process and osteoarthritis share biological factors in common, including oxidative stress and low level chronic inflammation."

    Link: http://www.sciencedaily.com/releases/2006/10/061001204429.htm

    Catching up with FasterCures

    It's been a while since I caught up on the activities of FasterCures (or the Center for Accelerating Medical Solutions), possibly not since the organization was launched back in 2004. At the time I was optimistic that FasterCures would head in the direction of "clearing out the undergrowth of political, regulatory and protectionist parasitism that holds back scientific progress and its commercial application." Their mission statement at the time:

    Evaluate the current systems of identifying and delivering cures

    Identify barriers to progress that currently exist in these systems

    Engage individuals and organizations in our mission to accelerate solutions

    Create action plans to clear the path to faster cures

    The present version of the mission statement is more refined, but essentially the same: the objective is systemic change. Unfortunately, all the signs are that reducing the influence of government and regulation is not on the agenda. Hence that aspect of FasterCures will wind up just another ineffectual talking shop and political advocacy group debating what color to paint the next damaging regulatory regime to come from the FDA.

    Oh well. Hopefully they don't pour too much money down that sinkhole before recognizing it for the waste it is.

    On the other side of the coin, FasterCures is sponsoring modest projects in the area of education and medical information exchange. Given the direction their advocacy is headed in, this work stands a greater chance of producing progress towards the FasterCures goal. The present state of medical information infrastructures is abysmal, to say the least, so even small projects have a chance of some beneficial effects ... assuming they are not squashed absolutely by the regulatory steamroller and its ever-expanding trailer of paperwork and requirements.

    I'll leave you with a pointer to a letter on disease and aging from the FasterCures president:

    If we were gathered here in 1906, not 2006, your lives would be very different - and I don't mean you wouldn't have an iPod. In 1906, one in five of you would have died before the age of five and wouldn't be here. You would already be near your mid-life crisis because you would be nearly halfway to your expected life. But the class of 1906 and all the classes after them created the greatest achievement of the last or any century - they doubled the life expectancy globally and increased it in the United States by 50 percent. Such an increase had never happened before in human history.

    What are we to think about such a gift from previous generations? For too many people - people who have not properly learned to think - greater life expectancy means more time to acquire more things like money, houses, cars, power. But you, you who have learned to think, know better. Having received this gift of greater life expectancy from previous generations, I hope you are thinking, 'How can I double my life's expectations?' Whatever you were expecting to do to educate, to care for others, to heal, to nurse, now is the time to realize you can do so much more because you have been given so much more time and so many more tools to do it.

    ...

    If you increase your life expectations, you who have learned to think about education and health, you can repay the gift of a longer life by giving people alive today, and those to come, a better life. You here today hold the greatest promise to improve and save lives through health education, faster and better research for cures, and improvements in public and global health.

    You hold this promise - you need to raise your expectations of how quickly and well you will fulfill it. But I am not asking you to cure death and suffering from cancer and a host of other diseases in your lifetime. I am asking you to do so in MY lifetime. With the Internet, the Human Genome map, modern computers and communication technologies, anything you can think about, you can understand, communicate and realize so much more quickly than any people in the history of the world.

    You don't get the whole century to make your mark. I have higher expectations for you than that. I said I was not going to give you advice and I meant it. This is not advice. I am giving you a mission. Your mission - our mission together - is to prevent the slow and painful wasting away of life so that people all over the world can lead full and meaningful lives.

    In summary: great promise, presently squandered. How bad will medical regulation in the US become before mainstream organizations form with the declared mission of tearing it all down? How much opportunity for progress will wasted, and how much health and life will be lost along the way? If Europe is any guide, it's a long way down to the bottom yet.

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    Chasing the Axon's End

    A recent New York Academy of Sciences meeting examined the potential for regeneration in the central nervous system: "Long regarded as unyielding territory by neurobiologists and neurologists alike, the capacity of the adult central nervous system (CNS) for growth is at last being revealed, along with its limitations. Just within the past few years scientists have discovered that neurons - the information-processing cells of the brain - can multiply in the adult, an idea that was previously unheard of. Adult neurons can also form new axons, the long extensions that allow neurons to form connections and thereby communicate. With this new understanding comes the need to identify growth-promoting signals. If such signals could be controlled, it might be possible to spur the establishment of new connections between neurons and, ultimately, to treat previously incurable neurological problems."

    Link: http://www.nyas.org/ebriefreps/main.asp?intSubsectionID=4312

    More On Regenerative Research

    Via the LEF News, more media attention given to attempts to replicate the regenerative abilities of lower animals and a very few mammals: "Buoyed by recent genetic breakthroughs, researchers at Northwestern University and across the country have hopes of achieving a feat long thought to be impossible: enabling people to replace damaged body parts or even regrow missing limbs. ... All of a sudden, this becomes not so much science fiction but really a challenging science problem. This particular project to regrow digits and limbs on humans is kind of like saying we're going to go to the moon ... There is a transition in us humans where we go from a perfect wound healing phase through regeneration early on, to a later phase where scars begin to form. That means we probably also possess the appropriate genes to perfectly heal wounds without scars. And that's the idea my colleagues and I have - to see if we can find the regeneration switch and reactivate it in humans."

    Link: http://www.lef.org/news/LefDailyNews.htm?NewsID=4399

    Cancer Vaccine Work Progresses

    A summary article from an ABC station reminds us that work on cancer vaccines continues to move forward: "The study to create a new solution to pancreatic cancer [median survival from diagnosis is around 3 to 6 months; 5-year survival is much less than 5%] is headed by Dr. Laheru and has been in progress for about two years. The researchers are using surgery, chemotherapy, and radiation, but are supplementing it with a new vaccine. The vaccine uses cancer cells that are stunted in growth that emit a certain molecule called GM-CSF. This molecule attracts cells that still have immunity to the tumor and causes them to come in contact with antigens from cells that have been exposed to radiation. These same cells then travel around the body and annihilate other cancerous cells. Patients receive the vaccination eight to 10 weeks after surgery and again after chemotherapy and radiation in a series of four booster shots. Two years into the study, the statistical results are optimistic. Of the 60 patients in the study, survival rates are reported to be 88 percent after one year and 76 percent after two years."

    Link: http://abclocal.go.com/kgo/story?section=edell&id=4605594