Telomeres, Correlation and Causation
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From Ouroboros: "Is telomere length important to the mechanism of aging, in addition to being a marker of advanced chronological age? The jury is still out on that, likely frustrated by the circumstantial nature of the evidence. We know that telomere length appears to be inversely proportional to life expectancy, but of course correlation [does not imply] causation, and lifespan and telomere length could be unrelated signifiers of the same underlying phenomenon. To complicate the issue, we are reminded in a recent review that all telomere ends are not equal ... bulk telomere length might be less important than the lengths of particular telomeres, a forest hiding the most significant trees. More to the point, the telomere lengths of the various chromosomes might be regulated independently, making bulk telomere length something of a red herring." A number of different research groups and young companies are presently working on therapies based upon altering telomere length; expect to see new knowledge and clarity in the field over the next five years.

Link: http://ouroboros.wordpress.com/2007/09/28/telomeres-and-aging-justifying-what-the-ends-mean/

Another Path to Mouse Longevity
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There are many ways to engineer mammalian metabolism for greater longevity, and more are discovered with each passing year. Any significant upgrade is likely to be a greater challenge to deploy in humans than repairing the metabolism we have, however. Here's a more impressive than average new example of engineered mice; these overexpress PEPCK-C, or Phosphoenolpyruvate carboxykinase. Note that the full PDF-format paper is freely available: "These mice were seven times more active in their cages than controls. On a mouse treadmill, PEPCK-C mice ran up to 6 km at a speed of 20 m/min while controls stopped at 0.2 km. ... The PEPCK-C mice eat 60% more than controls, but had half the body weight and 10% the body fat ... In addition, the number of mitochondria and the content of triglyceride in the skeletal muscle of PEPCK-C mice was greatly increased as compared to controls. PEPCK-C mice had an extended life span relative to control animals; mice up to an age of 2.5 years ran twice as fast as 6-12 month old control animals. We conclude that over-expression of PEPCK-C repatterns energy metabolism and leads to greater longevity."

Link: http://www.jbc.org/cgi/content/abstract/M706127200v1

Jealousy, Fear, Envy and Economic Ignorance - Powerful Poisons
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We humans possess some ugly instincts, hardwired into us over evolutionary time. The ape inside is not a pleasant fellow; he'd rather tear down pillars of success into a rubble of equal poverty for all than than use those pillars to raise up the areas between to a higher level of living. He's ever ready to believe the worst, to choose mysticism over science, hold the irrational beliefs of peers over demonstrated reality, and live in lazy ignorance rather than work to be educated.

All instincts can be mastered, and we are the masters of the ape inside - if we choose to be. Not a lot of mastering going on in the majority of the comments at AlterNet to a reprint on longevity science, however. I am always amazed at those people who stand convinced that new medical technologies and capabilities will be restricted to the "elites" - this flies so much in the face of even a cursory examination of the present day and recent history that it rises to the level of myth. It is a defining belief held as a part of tribal membership, divorced from any need to conform to reality. From this errant belief, it's a short slide into jealousy, envy and the tearing down of pillars - better all to die in poverty than any small group live longer.

And so, the barbarians.

Make no mistake, there are factions in our centralized, over-regulated, over-governed societies that aspire to call themselves "elites," enriching themselves at cost to the rest of us, parasites warring to leverage the mechanisms of the state to force their agendas. But you'll note that these "elites" - whomever you might think they are - have no greater access to medical technologies than any average fellow who takes care of his finances. This is the way the world actually works: new technologies move from dream to expensive, clunky reality to cheap and effective product in a fraction of a lifetime. So it was - and continues to be - for heart surgery, so it will be for gene therapy, and so it will be for the first true longevity therapies capable of repairing age-related cellular and biomolecular damage.

In the field of longevity medicine, as for all beneficial technologies under development, we all win together, or we all lose together. There is no other end to that story.

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On Preventing AGE Formation
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AGEs are bad news - a component of the biomolecular damage that causes aging, an ongoing buildup of compounds your body cannot break down rapidly enough, or at all in some cases. A branch of science, not as robust as we'd all like, focuses on how to break down AGEs, but there is always another approach: suppress their formation in the first place. At Ouroboros: "report that silks from several modern corn strains are capable of inhibiting nonenzymatic glycation in vitro, with the activity strongest in varieties bred to resist specific types of fungal infection. The mechanism of inhibition is not clear or even a ready subject for idle speculation (if you will, take a moment and bend your head around how one might specifically inhibit an uncatalyzed, non-specific reaction that can occur between a broad range of molecules); nor is it not obvious whether the phenolic compounds in the silk extracts could be made bioavailable without extensive modification. Still, once the chemistry of inhibition is elucidated, the silk-derived molecules could provide inspiration for therapeutics capable of stopping AGEs before they start."

Link: http://ouroboros.wordpress.com/2007/09/27/your-people-call-it-corn-my-people-call-it-maize/

CR in Practice and CR Research
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The Baltimore Sun looks at calorie restriction (CR) as it is practiced, and at a little of the latest research into CR biochemistry: "Known as calorie restriction, or CR, the Spartan diet is one of several avenues researchers are exploring in their quest to understand and delay aging. They're also interested in genes that appear to play a role in getting older, along with a variety of chemical compounds, including one found in red wine, that may possess life-extending properties. ... But assembling the clues to solve the aging puzzle is no easy feat. ... We know a lot more than when Ponce de Leon was wandering around Florida looking for the Fountain of Youth. But these things are tied together in ways that aren't completely understood. ... Even so, paragons of self-control [are] forging ahead, as are scientists intent on developing anti-aging therapies. ... Your hamburger could be turning off your longevity. But there may be ways to turn on the body's genes and to still protect you from diseases of aging."

Link: http://www.baltimoresun.com/news/health/bal-to.hs.longevity27sep27,0,309711,full.story

NYAS On Inflammation
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A recent briefing from the New York Academy of Sciences looks at inflammation, that great contributer to age-related degeneration:

The potential for destruction caused by dysregulated inflammation is apparent all around us. For just a few examples of potentially devastating chronic inflammatory diseases, consider irritable bowel disease, the spectrum of inflammatory rheumatic diseases, asthma, periodontal disease, and uveitis. Dysregulated inflammation in a wound, which prevents healing, illustrates an initially appropriate response that never turns off and thus never progresses to the next phase. In addition to these clinically obvious phenotypes, there is the far more subtle role - recently recognized - played by subclinical chronic inflammation as the invisible first step in a growing list of pathologies that currently includes cardiovascular disease, atherosclerosis, cancer, diabetes, and possibly depression.

Chronic inflammation is a real bugbear, and as the briefing notes, researchers don't yet know enough about metabolism to simply turn off inflammation. Inflammation itself is a process, the output of a very complex web of signals and interactions, a dynamic state in a dynamic system - you can't just block the river and hope for the best.

The model of inflammation and aging known as inflammaging is a helpful way of looking at why control of inflammation is a very desirable goal for those of us interested in healthy longevity; you might take a look at a paper on this model at the open access journal Immunity & Aging - I found it interesting reading.

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Do What You've Always Been Talking About
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I am always very pleased to see supporters of healthy life extension make the leap to activism and activity - if everyone who thought about living a longer life did but a tenth as much as Richard Schueler, we'd be much further along: "I love to talk about things I believe in. The subject that I’ve found myself telling people about the most the last few years is longevity research. If you CURE cancer and CURE heart disease, it adds 7 years to our life expectency. 100,000 people died yesterday from age. Yes, 100,000 real live people. They didn't die from starvation, they didn’t die from aids, they died from age. Why not work on something that can give us 3.5 years? 7.5 years? ... So I went a few years preaching and preaching about it, the world didn't change. ... So I made the next step. I decided to dedicate my life to the combat and elimination of age related diseases wherever possible. My fiancee [and] I bought our tickets for Cambridge, England and our tickets to the SENS3 conference, the largest conference in the world with a focus on age related disease and prevention. I met up with Aubrey de Grey a day before the show with the aim of finding where I would fit best in helping progress happen. I volunteered to take charge of the video of the event." And take charge he did; check out his website for a selection of conference video in processing. Do you want to see progress in healthy life extension in your lifetime? Then get out there and help those who are trying to make it happen.

Link: http://richardjschueler.com/2007/09/26/walk-the-talk-do-what-youve-always-been-talking-about/

Support for Alzheimer's as a Type of Diabetes
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You might recall intriguing research from 2005 that cast Alzheimer's disease as a form of diabetes. Here's more from EurekAlert!: researchers "have discovered why brain insulin signaling -- crucial for memory formation -- would stop working in Alzheimer's disease. ... a toxic protein found in the brains of individuals with Alzheimer's removes insulin receptors from nerve cells, rendering those neurons insulin resistant. (The protein, known to attack memory-forming synapses, is called an ADDL for 'amyloid beta-derived diffusible ligand.') ... ADDLS are small, soluble aggregated proteins. The clinical data strongly support a theory in which ADDLs accumulate at the beginning of Alzheimer's disease and block memory function by a process predicted to be reversible. ... ADDLs bind very specifically at synapses, initiating deterioration of synapse function and causing changes in synapse composition and shape. ... the molecules that make memories at synapses - insulin receptors - are being removed by ADDLs from the surface membrane of nerve cells. ... We think this is a major factor in the memory deficiencies caused by ADDLs in Alzheimer's brains. ... We want to find ways to make those insulin receptors themselves resistant to the impact of ADDLs. And that might not be so difficult." Note the important word in the middle there - "reversible."

Link: http://www.eurekalert.org/pub_releases/2007-09/nu-dst092607.php

Autographed Copies of Ending Aging
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I should point out that the Methuselah Foundation is offering a free copy of Ending Aging: The Rejuvenation Breakthroughs That Could Reverse Human Aging in Our Lifetime, autographed by biomedical gerontologist Aubrey de Grey, with any donation of $100 or more to Foundation-sponsored longevity research:

In Ending Aging, noted biomedical gerontologist Aubrey de Grey takes us on an engaging journey, detailing the path to a future in which we do not have to become frail and decrepit as we grow old and wise - and showing how we can get there within our lifetimes.

You can help support this goal and get a free autographed copy of Ending Aging with a donation of $100 or more to the Methuselah Foundation, a 501(c)(3) registered charity. Donations by US citizens are tax-deductible and all donations will be matched 1:2 by Peter Thiel.

Peter Thiel, you might recall, set up a $3 million matching fund for donations to Strategies for Engineered Negligible Senescence (SENS) research in 2006. Foundation donors are working their way through this fund - but more is always better.

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Growing Neurons To Order
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(From EurekAlert!). One aspect of research into controlling cells to keep an eye on: growing neurons to order. How much support can a carefully controlled supply of new neurons provide for an aging brain? Researchers are applying their first efforts to answer this question towards the repair of named neurodegenerative conditions: "The team used gene therapy to guide the development of endogenous stem cells in the brains of mice affected by a form of Huntington's. The mice that were treated lived significantly longer, were healthier, and had many more new, viable brain cells than their counterparts that did not receive the treatment. ... While the promise of stem cells is broadly discussed for many diseases, it's actually conditions like Huntington's - where a very specific type of brain cell in a particular region of the brain is vulnerable - that are most likely to benefit from stem-cell-based therapy ... Once we worked out the molecular signals that control the development of these brain cells, the next logical step was to try to trigger their regeneration in Huntington’s disease."

Link: http://www.eurekalert.org/pub_releases/2007-09/uorm-scs092407.php

SENS3 Science Report at Ouroboros
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Okie of Ouroboros reports on the recent SENS3 conference: "As a scientist, it is a challenge to present my work to a mixed group of scientists and (particularly well-educated) lay people. Where translational research is concerned, however, I think that lay people do a great job keeping us researchers focused on the prize and not just on (interesting) esoteric points." Okie goes on to give a punchy overview of the science presented, ending with: "I would like to see more theoretical and statistical work on which problems of aging are the most pressing/serious ones. I think Aubrey's '7 deadly things' is a well thought out plan for tackling the problem of universal aging. What I would like to see is some data on which problem(s) are rate limiting. For example, what if solving the problem of 'too few cells' (cell death and senescence in aging) would double human lifespan all by itself while all the others put together would barely accomplish the same? The keynote talk (by Ryan Phoenix) included some modeling of how soon SENS treatments could be available, how soon we would need to solve the 7 things in order to treat people alive today, and how often treatments would need to be repeated. This all relied, however, on the assumption than all 7 deadly things were created equally. Everyone agrees that we should take steps to provide the most immediate benefits to humankind, but no one agrees on what these are."

Link: http://ouroboros.wordpress.com/2007/09/25/conference-report-sens3/

On the Inevitability of Radical Life Extension
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The choice of living a healthy, youthful life of centuries and more is inevitable - it will come to pass. That much is obvious, written in the present breadth of human civilization, knowledge of what is possible under the laws of physics, and pace of progress in biotechnology. Replacement biological organs are a decade away, and commercial efforts to develop sophisticated repairs to age-damaged cells and vital biomechanisms will be rife in the 2020s. Computational power will be so great and so cheap that tens of thousands and then millions of research programs will be accomplished in simulation for a tiny fraction of their cost today; the priesthood of bioscience will dissolve and progress will be as diverse, energetic and imaginative as it is for open source software today. Redesigning human biochemistry and (greatly) augmenting our biology with nanomachinery will be hot areas for venture funding in the 2030s and 2040s.

"All" we need to do is to repair ourselves. The new bio- and nanotechnologies of the 2040s will be massive overkill for the "simple" task of repairing the damage of aging. The only thing stopping us from being able to do the job with the projected technologies of 2020 is that (a) we haven't yet proven our vision for success is accurate in its details, (b) support for the task at hand has yet to rise to the levels needed for success on a short timeframe.

The technology to enable youthful life spans of centuries is inevitable in the fullness of time - as the cost of developing an application of medical technology falls, the level of support required to complete the task falls with it. Sooner or later, a determined group will gather to get the job done.

So, to the point: the technology base required for the repair of aging is inevitable in the next few decades. Its application to this end, however, is not. That means that radical life extension is not inevitable for you and I; we're going to have to work on making it happen.

As is usually the case, achieving great goals across mere decades is far more a matter of persuasion than endeavor. The path is very clear and very plausible - if we can just convince a great many people to see things the same way and help out.

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Looking to the Future of Stem Cell Medicine
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The next decade will see ever more ambitious stem cell medicine made commercially available, very much despite the regulatory and legislative atmosphere at present. From the Sunday Herald: "Stem cells are primal cells at an early stage of development. Scientists hope to use their properties to study diseases and to develop 'repair' kits for the body by enabling healthy tissue to be grown. ... researchers around the world were already considering the use of stem cells to repair corneas, bones and specific cases of spinal cord injury. ... New therapies are just the same as medicines, they have to be tested and shown to be effective and safe. So it will be a small number of cases and a small number of treatments first, which will grow over the years and the decades. If you look back to when, for example, antibiotics first came along, there was a small number of them, but progressively they became more and more effective and now we take them for granted."

Link: http://www.sundayherald.com/news/heraldnews/display.var.1708374.0.stem_cell_therapy_will_be_commonplace.php

Aubrey de Grey at the Boston Stem Cell Summit
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As noted at the Methuselah Foundation blog, biomedical gerontologist Aubrey de Grey will be speaking at the Boston Stem Cell Summit early next month: "Following the successful conclusion of the third SENS conference in Cambridge, and the recent publication of my book, 'Ending Aging', which has received uniformly favourable reviews, I feel that we're turning the corner - the plausibility of retarding and eventually reversing aging is beginning to percolate into the public consciousness. A telling sign of increasing mainstream acceptance of our work at the Methuselah Foundation is the invitation I recently received to speak at the prestigious Stem Cell Summit to be held in Boston on October 2nd and 3rd. On 3rd October I will be attending the session on aging, followed by heading a table at the 'Conversations with Experts' luncheon." Late notice, I know, but supporters of healthy life extension research might want to attend - the conference is an interesting one, quite aside from any Methuselah Foundation presence.

Link: http://blog.methuselahfoundation.org/2007/09/aubrey_de_grey_at_the_boston_s.html

A Novel View of Cancer Stem Cells
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I follow developing work on cancer stem cells with some interest; there is at least some chance that a focus on cancer stem cells will lead to a grand simplification in treating many forms of cancer. Simplification here means a clearly identifiable type of cell to attack to stop a particular cancer in its tracks. A requirement to destroy specific clearly identifiable classes of cell plays to the strengths of biotechnologies now in development, and any area in which this is the case will see very effective therapies a decade from now. This would be a wonderful thing in the case of cancer, a most fearsome age-related condition, the malfunctioning of our most fundamental biochemical machinery. We should all be concerned about the cancer with our name on it; it's waiting out there for you to live long enough to meet it.

Nature recently published a novel perspective on cancer stem cells and the backstory behind how we ended up with the biochemistry we have. Well worth reading as a good example of how researchers attempt to fit theories around the evidence to date:

Our cells are constantly being replaced in vast numbers: the human body typically contains about a hundred trillion cells, and many billions are shed and replaced every day.

If this happened simply by replication of the various specialized cells in each tissue, our tissues would evolve: mutations would arise, and some would spread. In particular, mutant cells that don't do their specialized job so well tend to replicate more quickly than non-mutants, and so gain a competitive advantage, freeloading off the others. In such a case, our wonderfully wrought bodies could grind to a halt.

...

To renew themselves, epithelial tissues retain a population of undifferentiated stem cells, like the unformed cells present in embryos, that have the ability to grow into different types of cells. When replacements are needed, some of these stem cells divide to make transient amplifying cells (TACs). The TACs then divide several times, and Pepper and his co-workers think that each division produces cells that are a little more developed into mature tissue cells.

All this costs a lot of metabolic energy, so it is not very efficient. But, the researchers say, it means that the functions of self-replication and proliferation are divided between separate groups of cells. The stem cells replicate, but only a little, and so there's not much chance for mutations to arise or for selective pressure to fix them in place. The proliferating TACS may mutate, but they aren't simply copying themselves, so there isn't any direct competition between the cells to create an evolutionary pressure. As a result, evolution can't get started.

...

Whereas conventional wisdom has it that cancer is caused by some genetic mutation that leads cells to proliferate uncontrollably, this new picture implies that the problem would lie with TAC mutations that interfere with differentiation - so that a TAC cell ends up just copying itself instead of producing cells on the next rung up on the way to mature tissue cells.

Under this viewpoint, complex organisms - and our bodies - have evolved over generations to not evolve within a lifetime. Evolved to be cooperative machinery, rather than a collection of cells all trying to get ahead as individuals. Cancer is a breakdown of the mechanisms of cooperation, making cells act more like selfish bacteria in a petri disk and less like a well-tuned machine.

As for other theories on cancer stem cells, this work points out a clear and defined set of characteristics to look for if you want to destroy cancer cells before cancer even gets underway. Work in the lab will validate or disprove this line of thinking within the next few years at the present pace of progress. Very promising times we live in.

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p53 and Fly Longevity Again
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You might recall that researchers have achieved some success in extending fly longevity via p53 - a cancer suppression gene in humans, but also related to the biochemistry of calorie restriction. Via ScienceDaily, more on that line of research: "Bauer spent a year conducting painstaking experiments. He'd take a batch of young flies, each genetically altered to reduce p53 activity in a small portion of their nervous systems, and watch the flies age. Time and again, the flies lived for about two months - the average lifespan for these insects. But when Bauer manipulated a cluster of 14 insulin-producing cells in their brains, the flies lived about 15 to 20 percent longer. ... Bauer and Helfand then wanted to know if this was caloric restriction at work. So [they] restricted the diets of the flies and ran the same experiments. The calorie-restricted flies didn't live any longer when p53 was reduced in the insulin-producing cells. This evidence supports the notion that p53 reduction is one of the direct effects of caloric restriction."

Link: http://www.sciencedaily.com/releases/2007/09/070920161313.htm

Aubrey de Grey in AARP
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I have been patiently waiting for the AARP magazine's piece on Aubrey de Grey to become available online; finally, here it is: "Viewing old age as an 'engineering system failure' (and the phrase 'successful aging' as a contradiction in terms), Aubrey leapfrogged the ambiguous medical questions that paralyzed his peers and went straight to fix-it solutions. 'We don't have to understand the weather to repair the roof after a storm,' he insists with the bravado that drives his critics nuts. Aubrey dubbed his seven-step strategy SENS, which stands for Strategies for Engineered Negligible Senescence. It consists of seven baseline causes of aging, dealing with general types of cellular damage, and offers repair methods for each. Eliminate that cellular damage and, he believes, we could live to 125 and beyond in disease-free bodies that simply do not age. ... He has many credible defenders, including Anthony Atala, M.D., director of the Wake Forest Institute for Regenerative Medicine, who has called him 'highly visionary.' Even scientists who staunchly refute SENS, such as renowned University of Illinois at Chicago scientist S. Jay Olshansky, Ph.D. (who duked it out with Aubrey last year on CBS's 60 Minutes), cannot deny the benefits of his rabble-rousing. 'Ideas are the currency of science,' Olshansky says. 'Aubrey is developing an important currency, which I really appreciate. He's getting research scientists to think outside the box."

Link: http://www.aarpmagazine.org/health/big_idea_long-distance_living.html

The Waste, the Waste
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Some good points made in the discussion to a post on the low cost-effectiveness of government-funded medical research:

Writing in The Scientist Frederick Sachs argues that the large increase in funding for the US National Institutes of Health did not produce a commensurate increase in scientific productivity as measured by papers published.

...

Geez. An inefficient, ineffective, socialist, bureaucratic research system (as measured by its failure to cure most anything over 40 years) hits diminishing returns...

Am I the only one not surprised?

Sublimate it as rapidly as possible into a free-market, sink or swim, enterprise and maybe we will see something good come of it.

That point is made at greater length and in greater detail in the comments by those who work inside the system. It's an important point for people with an eye on the next few decades of progress - if you want to see significant results in the advancement of human longevity, merely throwing resources at the problem is inadequate in and of itself. Without the right incentives, accountability, freedom and community, there will be immense waste, and the immense cost of missed opportunity. All spending by centralized government bodies is of that nature; no incentives for progress, no accountability for failure to achieve, and every incentive to keep money flowing above all else. Human nature leads to an inevitable mess - and we should be smarter than that by now.

It should not be at all surprising to see bloated funding and no benefit to show for the increase - that's the story across the board in government programs, and we all suffer for it.

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The Latest on Calorie Restriction Biochemistry
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Via EurekAlert!, we note that Sinclair's research team are exploring the role of SIRT3 and SIRT4 in calorie restriction biochemistry: "Mitochondria, a kind of cellular organ that lives in the cytoplasm, are often considered to be the cell's battery packs. When mitochondria stability starts to wane, energy is drained out of the cell, and its days are numbered. ... SIRT3 and SIRT4 play a vital role in a longevity network that maintains the vitality of mitochondria and keeps cells healthy when they would otherwise die. When cells undergo caloric restriction, signals sent in through the membrane activate a gene called NAMPT. As levels of NAMPT ramp up, a small molecule called NAD begins to amass in the mitochondria. This, in turn, causes the activity of enzymes created by the SIRT3 and SIRT4 genes - enzymes that live in the mitochondria - to increase as well. As a result, the mitochondria grow stronger, energy-output increases, and the cell's aging process slows down significantly. (Interestingly, this same process is also activated by exercise.) ... We're not sure yet what particular mechanism is activated by these increased levels of NAD, and as a result SIRT3 and SIRT4, but we do see that normal cell-suicide programs are noticeably attenuated."

Link: http://www.eurekalert.org/pub_releases/2007-09/hms-rfc091707.php

A View of Aging and Longevity Research
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Here's a piece from Legion Magazine I missed earlier this year: a high level view across the voices and aspects of aging and longevity research. "De Grey believes it will be possible to postpone aging indefinitely - even up to the age of 1,000 - by adopting an 'engineering' approach to taking care of our bodies. In his approach, the cellular damage that occurs as a 'side effect' of being alive is allowed to occur, but it is then repaired using interventions such as stem cell therapy ... Additional significant increases in life expectancy can only come from advances in biomedical technology that alter the course of aging itself ... Perrott believes such advances are around the corner, and that they will relieve the suffering and social burdens brought on by age-related diseases and frailty. ... There's just an awful lot of hope. People like to get old; they just don't like falling apart. Right now, the priority is to get people healthy. Then we can work on life extension. ... Whereas it used to be thought that aging was 'way too complex' to tackle as a whole, and that different diseases were caused by a host of different things going wrong, he points out that in the last 15 years, science has shown that 'there may be only a few causes of many diseases,' and indeed only a few causes of aging."

Link: http://www.legionmagazine.com/features/healthlifestyle/07-07.asp

A Raft of Papers on AGEs, ALEs, RAGE
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The latest issue of Molecular Nutrition & Food Research plays host to a debate on advanced glycation endproducts (AGE), their receptors (RAGE) and advanced lipoxidation end-products (ALEs). The latter are oxidized lipids suspected as a mechanism by which reactive oxygen species wreck havoc throughout the body - the free radical theory of aging.

It is rather interesting to see the biogerontological viewpoint - AGEs are one root cause of aging, or at the very least a range of age-related disease - presented in debate with the nutritionist's viewpoint of "we eat these things in volume with no ill effects, so of course they're safe." I massively oversimplify both sides in that statement of course, but the nutritionist's view might be equated with the view of aging and age-related degeneration as "normal." In any case, a representative sample of the papers on offer:

Dietary advanced glycation endproducts (AGEs) and their health effects:

Thermal processing of food results in the formation of various novel compounds, among others advanced glycation endproducts (AGEs). AGEs result from nonenzymatic glycation reactions between reducing sugars and free amino groups of proteins, peptides, or amino acids. Due to their potential noxious effects, alimentary AGEs are also called glycotoxins. This review provides a summary of the available evidence on the health effects of exaggerated intake of thermally treated food. Data from experimental studies in rodents and from clinical studies in healthy volunteers and in patients suffering from selected diseases in which AGEs are of pathogenetic importance (diabetes, chronic renal failure) are summarized. It is concluded that, an exaggerated intake of thermally processed foods may exert in vivo diabetogenic and nephrotoxic effects, induce low-grade inflammation, enhance oxidative stress, and promote atherosclerosis.

Food intake is only one source of AGEs, however - and it may not be the most important one for people following a sane diet. Your own metabolism cheerfully churns out AGEs of many different varieties. Over the years, those that cannot be effectively broken down will damage and hinder your biochemistry ever more seriously. Progress towards AGE-breaker drugs - and other technologies like bioremediation - capable of safely removing these damaging compounds is one important facet of longevity science.

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Understanding Life Expectancy
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The American Scientist is running a great piece on the measurement of life expectancy, and how the modeling of life expectancy overlaps with progress in the science of aging: "The systems-based explanation argues that complex machinery fails because many things go wrong. According to this model, as with your Toyota, so too with your body: The force-of-mortality curves for automobiles (called failure-rate curves) complied by demographers [bear] an uncanny resemblance to their human counterparts. Both human and automobile curves show an exponential increase in the force of mortality that tapers off in later years ... Surprisingly, mortality in the early years is eerily similar in people and automobiles: Defects in manufacture (machines) or development (organisms) reveal themselves early on. ... Such systems, whether we speak of Toyotas or biologists, are characterized by redundancy brought about by engineering (in the first case) or evolution (in the second). But, as University of Chicago gerontologists Leonid Gavrilov and Natalia Gavrilova have argued in their influential book The Biology of Life Span: A Quantitative Approach, the very redundancy that permits complex systems to endure a constant rain of light damage also allows such damage to accumulate, resulting in aging and eventual failure."

Link: http://www.americanscientist.org/template/AssetDetail/assetid/55855?&print=yes

Arnold Kling Reviews Ending Aging
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Arnold Kling reviews "Ending Aging: The Rejuvenation Breakthroughs That Could Reverse Human Aging in Our Lifetime" at TCS Daily: "Too often, academics use their credentials to spit out biased polemics dressed up as science. Ending Aging is the opposite. It is a crash course in state-of-the-art science dressed up as a polemic. De Grey wears his passion for undertaking a war on aging on his sleeve, yet most of the book consists of scientific analysis that, although simplified to enable a layman to follow, is conscientious in reporting doubts and objections to the author's point of view. ... It gives a sense of the possibilities, drama, and frustration of scientific inquiry. Also, it might inspire some young geniuses to undertake the sort of investigations and experiments that de Grey thinks will help win the war against aging. ... Today, the incentives to experiment with general-purpose anti-aging technologies are limited. Only if a technique can be demonstrated as helping to treat a specific disease can its development be funded and its efficacy tested in humans. Of course, many of the techniques necessary to achieve de Grey's vision can be shoehorned into a disease-fighting agenda somewhere, which is why he can report results that justify his belief in the potential to conquer aging. However, there remains the fact that the current system gives too much incentive to find stopgap solutions to specific diseases and too little incentive to develop general-purpose anti-aging technologies."

Link: http://www.tcsdaily.com/article.aspx?id=091207G

Reports From SENS3
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I'm somewhat late in directing your attention to the science reports from the third conference on Strategies for Engineered Negligible Senescence, but here they are. In my defence, I did mention them in Monday's Longevity Meme newsletter - one of many good reasons to subscribe.

We'll start with a look at the range of research presented on repair or damage prevention for mitochondrial DNA, one root cause of aging. You'll find an outline of the process by which damage to the mitochondria in a small portion of cells can lead to significant accumulated biochemical damage throughout the body back in the Fight Aging! archives.

SENS3 Report: Towards Mitochondrial Repair:

Dr. Samit Adhya of the Division of Molecular and Human Genetics at the Indian Institute of Chemical Biology is pursuing yet another innovative approach. He proposes to dispense with the need for mitochondrial DNA altogether, by instead providing the mitochondrial protein-making machinery directly with the "working instructions" (messenger RNA) that it normally receives in the form of a transcribed copy taken from the mitochondrial DNA originals. This would allow the mitochondria to continue their protein production even if the mitochondrial DNA were completely destroyed: they would still have their marching orders, even if the general himself were incommunicado. Dr. Adhya is accomplishing this goal by borrowing a trick used by a single-celled organism called Leishmania tropica. This organism, unlike mammals, generates another kind of RNA in the main cell body, and uses a specialized protein to move it into the mitochondria. Dr. Adhya reasoned that he could bind copies of our own RNA to the same protein and use it to deliver both kinds of RNA into mammalian mitochondria, bypassing the need for a DNA original. Very clever.

The Leishmania research was in the news late last year, if you want to take a look at one of the scientific papers from Dr. Adhya's team:

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.

SENS3 Report: the GIFT Versus Cancer:

Last year, Dr. Cui electrified the world when he showed that the [cancer-fighting abilities of a new strain of mice] were caused by a particular subset of their immune cells -- members of a class of white blood cell known as neutrophil granulocytes. These cells are from the innate immune system, meaning that they don't have to "learn" to identify a narrowly-defined enemy, but are constantly on the lookout for broadly-defined "foreign" cells. They are a kind of phagocytic cells, surrounding, engulfing, and digesting their targets when they find them.

Dr. Cui tested the ability of these cells to fight off cancer by transfusing them into normal mice with cancers. Surprisingly, the simple transfusion of the cancer-fighting immune cells from the resistant mice effectively transfered the same remarkable protection to the normal mice. And even more excitingly, the treatment didn't just prevent cancers from forming, but actually fought off existing cancer: when researchers transfused the anti-cancer white blood cells into normal mice with existing skin tumors, the tumors regressed completely in a matter of weeks. Moreover, a single dose of the cancer-fighting immune cells gave the normal animals a cancer immunity that often lasted for the rest of their lives.

At SENS3, Dr. Cui presented the next logical step in his research: work demonstrating the existence of, and characterizing, high-potency cancer-killing granulocytes in humans.

You might have seen overly excited press articles on this research turning up in recent days - journalists have a way of mangling information on timelines into something much more sensational than is in fact the case. Dr. Cui's work is important, and an impressive technology demonstration, but still pre-trial and one of dozens of just as effective demonstrated means to kill cancer. We should be so lucky to be spoiled for choice when the cancer with our name on it arrives.

Lastly, I should point out the post-conference blogging taking place at the Frontier Channel - starting with the author, Aubrey de Grey and Michael Rae in the Anchor Pub, discussing advocacy for healthy life extension:

I had my first conversation with Michael Rae. We talked about Christopher Sykes' recently-widely-net-viewed documentary "Do you want to live forever?", which focuses on Aubrey. Michael had said in a Methuselah Foundation forum post that he intensely dislikes it. I wanted to know why.

I thought its excellent production values and on-balance pro-Aubreyness overcame its cartoonishness, contrived melodrama, shallowness, and emphasis on sex and sentiment. Combining heads with Michael I'm not sure whether or not its existence is a net favor.

I think what Joe Layboy takes away from the film is "there's this weirdo genius dude who thinks he can make us live forever and what's next on the telly?"

Vastly preferable would be to make Joe Layboy incredibly mad that we're all going to die and only 1 in 1,234,567 people are doing anything about it.

Our best minds haven't yet succeeded in inciting riots. The first great documentarian of our movement might figure out how.

Inciting quiet, focused riots of research and support for healthy life extension is indeed a worthy goal for the advocates - and we haven't yet hit on the key to amazing growth or instant understanding and support. I suspect that, like most successful movements in history, this is going to require a number of years and hard work by a great many people.

That said, that work is underway. Progress is definitely being made; the sales and reviews of Ending Aging, the attendance at SENS conferences, positive media attention week after week and funds raised by the Methuselah Foundation for research are all good yardsticks. We can and will raise a research community and gathering of supporters to match that presently focused on cancer - these are the early days in a growth trend, and the best time to jump in and help out.

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Engineering the Immune System to Kill Cancer
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Another good technology demonstration for cancer immunotherapy from ScienceDaily: "Human white blood cells, engineered to recognize other malignant immune cells, could provide a novel therapy for patients with highly lethal B cell cancers such as acute lymphoblastic leukemia (ALL) ... By administering repeated doses of T cells designed to express an artificial receptor which recognizes human B cells, the researchers were able to eradicate cancer in 44 percent of mice bearing human ALL tumors. ... The immune system has evolved to police the body for infections and diseased cells, but it has a difficult time recognizing malignant cells since they largely appear normal to the immune system. The idea is that we can take a patient's own T cells, re-educate them by inserting a gene into them that will enable them to produce a receptor to recognize B cell cancers, and then return them to the patient where they should be able to attack and kill the tumor cells." Highly efficient, cheap and widespread cures for cancer are only a couple of decades away; the breadth and pace of present research is very encouraging.

Link: http://www.sciencedaily.com/releases/2007/09/070918090753.htm

Aubrey de Grey on New York Public Radio
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Biomedical gerontologist Aubrey de Grey was interviewed for the Leonard Lopate Show on WNYC New York Public Radio just recently. He talks about the Strategies for Engineered Negligible Senescence (SENS), his new book "Ending Aging: The Rejuvenation Breakthroughs That Could Reverse Human Aging in Our Lifetime", and the concepts of actuarial escape velocity. You can stream or download the audio recording from the WNYC website: "Will people in the future suffer mid-life crises at the age of 100? Many biologists believe that someday we will be able to substantially slow down the aging process, but Dr. Aubrey de Grey is perhaps the most bullish of all such researchers. Dr. de Grey believes that the biomedical technology – that may eliminate aging-derived debilitation and even death entirely – is now within reach. Ending Aging explains the process of aging, and how this biotechnology may reverse age-related decay." The comments posted online make for interesting reading - a real range of opinions. It seems to me that the proportion of positive, pro-longevity voices is growing.

Link: http://www.wnyc.org/shows/lopate/episodes/2007/09/18/segments/85675

A Mortality Risk View of Aging
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An article I stumbled across today, lightweight as it is, convinces me that measuring aging by mortality risk is more elegant that the traditional method of counting years. Doing so factors in some degree of ongoing progress in medical science, some degree of the ongoing accumulation of cellular and molecular damage, and I'm an easy sell for any yardstick that manages that.

He argues that age should be calculated not by years since birth but by years left to live. With data from the 2000 census, he has reconfigured the calendar of aging ... according to his mortality risk measure, you aren't old unless you have a 4 percent risk, Shoven says. That's a 1-in-25 chance of dying within the year, which could well translate into a lengthy old age. Today people don't begin to get old until their 70s. Middle age - defined by a mortality risk between 1 and 4 percent - doesn't start for a man until he is 58!

Just like dollars, years of age don't have the same value as they did in the past. In 1940 a man in his late 40s had the same mortality risk as a man in his late 50s today. A woman in 1940 crossed the threshold into old age when she was in her late 60s. Today she would be in her late 70s.

Neither years nor mortality risk from census data says anything about your deviation from the average, of course. How healthy are you, how much damage have you sustained? Those of us with an interest in personal longevity should all be working on pushing that deviation upward - every extra year of healthy life is worth a great deal when the rate of progress in biotechnology and medical science is as rapid as it is at present. Work your own way to an additional year, and you will benefit from another year of new technologies aimed at helping you live longer in good health.

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"Too Sciencey"
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As noted in an Immortality Institute discussion, Good Morning America cancelled on the scheduled airtime for Aubrey de Grey, the Strategies for Engineered Negligible Senescence and Ending Aging because the whole subject was "too sciencey."

It's somewhat sad that this great world-spanning society of ours, enabled entirely by the dedication of generations of researchers and supporters to science and the scientific method, now sees so many people wealthy and insulated enough to drift through life, ignoring the very foundations upon which their wealth rests. Our ancestors worked hard to lift us from poverty and grinding need, and here we are, dismissive of their sacrifices. Sad, but plain old human nature and economic inevitability at work. One of the Immortality Institute folk suggests:

This is a difficult message to weave as the scaling the scientific disciplines can be a daunting task alone never mind attempting to weave in the philosophical and humanitarian arguments that curing aging should be seen as one of the pinnacles of human achievement.

The idea of living forever cuts across the grain of so many indoctrinated cultural memes that even having this conversation with intelligent and open minded people is like asking someone to try and swallow a giant scoop of a new and bizarrely flavored ice cream on hot day. You're shocking them with an ice-cream headache and a taste-bud overload at the same time.

While casting a wide net like GMA Aubrey may get some 'hits' but in general, immortalists might be best served by studying the demographics in detail and crafting messages for particular groups.

Television is an interesting and increasingly irrelevant venue for actual communication; the work of the Methuselah Foundation has received far more benefit and exposure from a few presentations uploaded to YouTube than from all of the TV appearances of Aubrey de Grey put together. I am more encouraged by the response from other media, as illustrated by this review in the Deseret Morning News:

De Grey has seven categories he calls "the Seven Deadlies" — cell loss or atrophy, junk outside the cells, crosslinks outside the cells, death-resistant cells, mitochondrial mutations, junk inside the cells, and nuclear mutations such as cancer.

That means little to the uninitiated reader. But don't give up.

Central to de Grey's theory is his often-used analogy to automobiles. Essentially, most of us buy cars, and some cars last longer than others. Volvos usually last longer than Chevy Cavaliers. But most cars will go on if we fix the damage as it happens: "A car can be kept going more or less indefinitely with sufficient maintenance. ... We simply repair worn-out parts when they begin to fail."

...

Rae and de Grey attempt to treat these issues in a way that "any educated layman who's willing to put in the time to read it carefully" can understand. In the main, that appears to be true.

Or, much more so by this comment to one of the very scientific SENS reports at the Methuselah Foundation blog:

Thank you for this report! I found it through Ray Kurzweil's site. My awesomely brave husband, Gene, has lived with Leber's Hereditary Optic Neuropathy for 36 years. His vision keeps deteriorating and he fights to keep his spirit strong. This information is vital, not only in its eventual clinical application with humans, but in the hope it gives, right now, to people like Gene who were told that there was no hope. We are not highly educated people and I have great difficulty understanding the terminology and the technology used by these brilliant researchers, but I have to try for Gene. I just don't know what else to do. I search the internet almost every day for any information that might be helpful to LHON patients. Today I feel as though I have struck gold! I am printing a copy of this report so that I may read it over and over again until I gain even the loosest understanding of it. Dr. Alfredo Sadun is coming to our LHON fundraising dinner in Cleveland in October. I'll never be able to discuss this research with him intelligently. Maybe I'll just show him my copy of this article..then run away like Napoleon Dynamite! Again, thanks for the report!

"Too sciencey" is an arrogant nonsense, dismissive of people and their complexities. Folk work at and value what is important to them - and we still live in a culture that respects science, even if that sentiment is well hidden at times by the wealth created and piled high by the application of science.

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Bootstrapping to an Ageless Future
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Edge excerpts Ending Aging: "An important fact is that the therapies we develop in a decade or so in mice, and those that may come only a decade or two later for humans, will not be perfect. Other things being equal, there will be a residual accumulation of damage within our bodies, however frequently and thoroughly we apply these therapies, and we will eventually experience age-related decline and death just as now, only at a greater age. Probably not all that much greater either - probably only 30-50 years older than today. But other things won't be equal, and I'm going to explain why not - and why, as you may already know from other sources, I expect many people alive today to live to 1000 years of age and to avoid age-related health problems even at that age." It's a good explanation of the plausibility of actuarial escape velocity - the step by step process by which we could bootstrap our way to agelessness, one rejuvenation therapy at a time.

Link: http://edge.org/3rd_culture/degrey07/degrey07_index.html

Holding Back the Years
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The Observer is running a long article on the SENS conferences and the work of Aubrey de Grey and other gerontologists, starting with SENS2 in late 2005 and working forward: "Until recently a lot of people thought ageing was too complicated to ever get a real handle on. Someone described it rather graphically as like a car crash - everything just gets wrecked. The exciting thing about the current science is that we are becoming like sophisticated accident investigators. We can actually understand what influences the process of ageing and what parts of the body work most successfully to keep us in good health for as long as they do. The research is moving forward fast. ... During the conference I wander over to King's College to visit a friend struggling into his eighties with bronchitis, sciatica and other health problems. I feel a little embarrassed telling him about de Grey's theories, which shows how intoxicated I've become by the notion of a future where he will die soon and younger people will live for an extraordinarily long time. He listens patiently then recites the prayer to serenity: 'Give us the grace to accept the things that cannot be changed, courage to change the things that should be changed, and the wisdom to distinguish the one from the other.'"

Link: http://observer.guardian.co.uk/magazine/story/0,,2168142,00.html

SENS3 Posts From Attila Chordash
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Molecular biologist Attila Chordash continues to turn out posts on his favored presentations at the recent SENS3 conference on rejuvenation and longevity science. The view of researcher Michael Rose's approach to engineering longevity is interesting: "The script is: breed mice with delayed reproduction over multiple generations (let evolution by natural selection give us the answer of how to build a long-lived animal), and then reverse engineer this answer to develop anti-aging therapies for genetically unaltered humans. The experimental basis of this proposal: Rose's own ancient experiments with fruit flies [showed] that there is a plateau in mortality rates after many generations of breeded Drosophilas with delayed reproduction time which leads to the cessation of the aging process." This is an extension of the search for longevity genes; let evolutionary pressure do some of the legwork first, in terms of identifying the biochemistry that is most important. Still, fundamentally this is a reengineering approach, not a repair approach - and therefore most likely much harder.

Link: http://wordpress.com/tag/sens3/

Most People Won't Determine the Difference
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A post from the Digital Rules blog reminds us interest in healthy life extension is more widespread than we sometimes think. "The last day of the Forbes Global CEO Forum featured a rousing panel on life extension, which I moderated. How many years can you add to the span of your life if you do everything right ... diet, exercise, accident and disease prevention, etc? Five years? Ten? Twenty? More? What new drugs, diagnostics and cures now in development have the potential to add even more years to our lives - healthy years?" Sadly, it is also a reminder that most people will not exert the effort required to determine the difference between (a) nonsense and hype, (b) marginally useful good health practices, (c) forward looking longevity science that will in fact extend life significantly. Never mind distinguishing between probably ineffective and probably effective forward-looking longevity science. This is how the desire for longevity - expressed in the willingness to pay for progress and personal gain - is subverted into the waste and lies of the "anti-aging" marketplace. We must continue to raise the level of education regarding healthy life extension - by doing so, we help to steer resources to the research with the best chance of extending our healthy life span.

Link: http://blogs.forbes.com/digitalrules/2007/09/can-you-extend-.html

Rising Life Expectancy
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Articles on rising life expectancy will be a lazy journalistic staple in the mainstream from here on out - they write themselves, and you can push one out on autopilot every six months or so. The statistics even come superficially pre-analyzed these days; no thought needed by the media outlet at all. We'll ponder the irony inherent in this post while looking at the statistics:

Life expectancy rates in the United States are at an all-time high, with people born in 2005 projected to live for nearly 78 years, a new federal study finds.

The finding reflects a continuing trend of increasing life expectancy that began in 1955, when the average American lived to be 69.6 years old. By 1995, life expectancy was 75.8 years, and by 2005, it had risen to 77.9 years, according to the report.

Life expectancy is a subtle statistic - it doesn't measure quite what you might think it measures. But medicine is becoming more effective; we are indeed in an upward trend, the result of massive investment in medical and biotechnological progress.

It's a slow boat of a trend when it comes to additional years of life, however, and people are overly focused on trivial regional and cultural differences - half a year here, a year there. These are meaningless, useless exercises in comparison in the face of what is possible for medical science. We can see paths to extending healthy life by decades, to repairing aging in the very old to give them additional youthful years. Given the necessary support and funding, this technology could be mere decades away.

Ignore the slow trend upwards in health life; that trend is not the one to be watching. Keep an eye instead on the development of a research and funding community centered around real rejuvenation technologies. That is where meaningful healthy life extension will start.

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Understanding Retinal Regeneration
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Researchers continue to decipher the biomechanisms of retinal regeneration that take place throughout life, but fade in old age to cause blindness: "Rod cells make up the majority of photoreceptors in the human eye ... Rod cells contain tiny organelles called the 'outer segment,' which contain about 1,000 flattened discs containing rhodopsin - a visual pigment that absorbs light. Each day, our eyes shed the top 10 percent of these discs, but until now, no one really knew how the retina generated new discs. We believe we have solved that riddle ... There are currently more than 100 retinal eye diseases in human populations, and problems with rhodopsin trafficking or outer segment development are thought to play a role in many of these potentially blinding conditions. In fact, we got interested in this type of research because we knew that breakdowns in rhodopsin trafficking were crucial to a common eye disease, retinitis pigmentosa." Identifying mechanisms is very empowering in this age of biotechnology - it can lead quickly to targeted, effective therapies.

Link: http://news.med.cornell.edu/wcmc/wcmc_2007/09_10c_07.shtml

Eat Less, Live Longer
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KQED's QUEST recently aired a piece on the science of calorie restriction, discussing the past few years of research with scientists working at the Buck Institute for Age Research: "Have we found the fountain of youth? Scientists are discovering ways to make animals live dramatically longer through calorie restriction. While the technique has attracted a small, but devout following, skepticism abounds. ... Alzheimer's, Parkinson's, cancer, stroke, and arthritis have one thing in common: age. By focusing on the connection between aging and disease, scientists at the Buck Institute for Age Research are striving to develop diagnostic tests and treatments that will prevent or delay these conditions." Calorie restriction is not the fountain of youth for us - but it is a helpful way to raise our chances of living to benefit from the real rejuvenation medicine of future years. No fountain of youth exists today, but it is within our power to band together, research, and find out how to build medical technology to repair aging and make the old youthful once more.

Link: http://www.kqed.org/quest/television/view/569

Rejuvenation Research, Volume 10, Number 3
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The latest issue of Rejuvenation Research is up, and it's weighty, bulked out by papers from the Edmonton Aging Symposium held in March. The results presented by LysoSENS researchers funded by the Methuselah Foundation are worth pointing out again:

Engineering Away Lysosomal Junk: Medical Bioremediation:

Atherosclerosis, macular degeneration, and neurodegenerative diseases such as Alzheimer's disease, are associated with the intracellular accumulation of substances that impair cellular function and viability. Reversing this accumulation may be a valuable therapy, but the accumulating substances resist normal cellular catabolism. On the other hand, these substances are naturally degraded in the soil and water by microorganisms. Thus, we propose the concept of “medical bioremediation,” which derives from the successful field of in situ environmental bioremediation of petroleum hydrocarbons. In environmental bioremediation, communities of microorganisms mineralize hydrophobic organics using a series of enzymes. In medical bioremediation, we hope to utilize one or several microbial enzymes to degrade the intracellular accumulators enough that they can be cleared from the affected cells. Here, we present preliminary, but promising results for the bacterial biodegradation of 7-ketocholesterol, the main accumulator of foam cells associated with atherosclerosis. In particular, we report on the isolation of several Nocardia strains able to biodegrade 7-ketocholesterol and as an ester of 7-ketocholoesterol. We also outline key intermediates in the biodegradation pathway, a key step towards identifying the key enzymes that may lead to a therapy.

Medical bioremediation has a great future ahead of it - it's clearly one of those ideas, so obvious in hindsight, whose time has come. You should expect to see companies founded on applications of this technology base a decade from now, just as they are founded today on the application of calorie restriction science.

As an aside, and since we're on the topic of the Edmonton Aging Symposium, you should take a look at the video archive at the Symposium website - it's a great collection of presentations that touches on some of the most promising modern science relevant to aging, longevity, repair and rejuvenation.

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Cancer Stem Cells Drive Metastasis
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From The Scientist: "This is a confirmation of what a lot of people have been talking about, the hypothesis that cancer stem cells are the source of metastasis ... Although the study focused on pancreatic cancer, he noted, it could apply to many other tumors as well ... Recent research has suggested that some tumors, including breast, colon, brain, prostate, and most recently, pancreas, arise from a small subset of stem-like cells called cancer stem cells, which often are marked by the cell surface antigen CD133. These cells induce tumor formation and are often resistant to conventional therapies. Researchers assumed that some segment of these cells also drove metastasis, but this had remained unproven. ... [this] begins to put a definition on the cells responsible for metastasis." Cancer without metastasis would be much less threatening an age-related disease. If we're lucky enough to find that metastasis relies on a small, distinct population of cells, then we can expect significant progress over the next decade.

Link: http://www.the-scientist.com/news/home/53583/

Why Deathism?
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Thoughts from the Frontier Channel: "During the Singularity Summit 2007, one of the most unexpected moments came during a panel session on day one. Peter Voss and Dr. Stephen Omohundro sat down to answer questions from the audience after their own individual presentations. Voss had suggested during his talk that [artificial intelligence] could benefit health and longevity research. An audience member asked, with apparent anger and passion, why anyone would want to extend healthy lifespan and attempt to prevent death. Voss seemed surprised by the question, and asked the audience if anyone really wanted to die. A significant minority raised their hands, cried out, and applauded. A philosophical chasm was then suddenly laid bare, thought it appeared that neither side could wrap their heads around the alternative view. After Voss defended radical life extension, a larger portion of the crowd applauded. Why would anyone defend death, especially with applause?" Casual deathists are everywhere; I bear them no ill will, so long as they're not trying to cut my life short as well.

Link: http://frontierchannel.com/2007/09/12/applauding-death/

Nature Collections: Aging
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Every so often, Nature puts out a free collection of representative papers in a field. This time round, it's aging research over the past couple of years:

The world's population is ageing rapidly. The effects of this change in demographics are predicted to touch on many facets of human life. Not least, because the health of older people deteriorates with time. This Nature collection draws together recent articles on the process of ageing, and the connections that exist between growing older and disease.

Cannily sponsored by Sirtris, you'll note - raising a nine-figure stack of venture capital for the main order of business allows many associated perks along the way. Also worth noting: "free" means you can request a free print copy in addition to reading the papers online.

The biochemistry of calorie restriction, stem cells and cancer as it relates to aging forms the order of the day - a good first-order approximation of the weight of research in mainstream gerontology at present. Go and take a look. The focus is on the mechanical underpinnings of metabolism, and how those mechanisms could be changed to allow for greater longevity - very much the slow road forward, given the immense complexity of our metabolic processes.

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Engineering Stem Cells More Effectively
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Watch the progress of infrastructure technologies and techniques - it is solid improvement in the foundation that enables stunning advances at the top floor of applied biotechnology. Take this for example, published at Cell Stem Cell: "Reprogramming of somatic cells to the pluripotent stem cell state may allow the development of in vitro models of disease and could provide a mechanism for the generation of patient-specific cells of therapeutic interest. Reprogramming of mouse fibroblasts into induced pluripotent stem cells, or iPS cells, has been achieved with overexpression of oct4, sox2, klf4, and c-myc and drug selection for the reactivation of a marker of pluripotency ... Here we show that n-myc can substitute for c-myc and that drug selection is dispensable for reprogramming of fibroblasts to pluripotent stem cells. ... Our findings greatly simplify the method for induction of pluripotency and bring it one step closer to clinical applications." Generating pluripotent cells at will cheaply, quickly and reliably is a vital pillar for the ongoing development of regenerative medicine. The easier it becomes, the faster the field will move.

Link: http://www.cellstemcell.com/content/article/fulltext?uid=PIIS1934590907001270

Another Demonstrated Cancer-Killing Virus
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A number of research groups have demonstrated the use of engineered viruses for the targeted destruction of cancer cells. Here is another, aimed at cancer stem cells this time, via EurekAlert!: "We have shown first in lab experiments and then in stem cell-derived human brain cancer in mice, that we have a tool that can target and eliminate the cells that drive brain tumors ... The virus was tested against the most aggressive brain tumor - glioblastoma multiforme, which originates in the glial cells that surround and support neurons. ... Research has shown that these cancer stem cells are the origin of the tumor, that they resist the chemotherapy and radiation that we give to our patients, and that they drive the renewed growth of the tumor after surgery. So we decided to test Delta-24-RGD against glioma stem cells and tumors grown from them ... Fueyo and colleagues developed Delta-24-RGD to prey on a molecular weakness in tumors and altered the virus so it could not replicate in normal tissue. They showed [in] 2003 that the virus eliminated brain tumors in 60 percent of mice who received injections directly into their tumors. The virus spreads in a wave through the tumors until there are no cancer cells left, then it dies."

Link: http://www.eurekalert.org/pub_releases/2007-09/uotm-cvk090607.php

Timelines for Xenotransplantation
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If you want to replace age-damaged tissue, you have to source the replacement from somewhere. A primary focus in the biotechnology research community is tissue engineering - building new organs from a patient's own cells, controlled and aided by a wide variety of helper technologies. The same underlying tools of biotechnology also make another source of organs available: xenotransplants grown in gene-engineered animals. An article from the UK press puts forward a timeline for clinical use similar to that for tissue engineered complex organs:

British scientists could be breeding designer pigs in just two years that would offer hope to transplant patients. ... Although the work, being carried out at Imperial College London, is still in the early stages, he is confident of producing the first designer pigs within two years. This means organs grown in pigs could be used in human transplants within a decade.

...

The research, presented at the British Association's Festival of Science in York, centres around tricking the body's immune system to believe that pig organs are human. This is done by creating pigs carrying genes which alter key molecules on the surface of organs, hiding their origin from the human immune system.

...

But EU regulations mean that the researchers have so far been refused permission to breed from the pigs. This, combined with a 13-month delay for Home Office approval to inject the gene into the pigs, means further research may be carried out in the U.S.

So far, the alterations to the pigs' sperm have only been temporary. But within two years, the scientists hope to have been successful in making long-lasting alterations - and in the birth of designer offspring. Many more years of work will then focus on using genes thought to be able to trick the human immune system, and, finally, on testing the technique on people, with human transplants ten to 15 years away.

A familiar story, and familiar ball and chain.

Regulation aside, xenotransplantation is likely to be competitive to tissue engineering for the forseeable future - perhaps right up until the time the two fields begin to blur and overlap. If an aspect of the biology of a different species is clearly superior to that of humans, and biotechnology offers us the ability to make use of that superiority, people will seize the opportunity. Perhaps more pertinently, ever increasing capabilities in biotechnology and molecular nanotechnology will, in decades to come, start to render cell structure, organ form, genes and even being biological a matter of choice. We are machines built upon machines, and soon enough there will be designers, repairmen, new versions and tremendous diversity.

The petty regulation and debate over every new advance in the first years of the 21st century will be seen as a parochial, fearful flight from opportunity by those who benefit from the biotechnologies to come.

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WSJ Review of Ending Aging
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The Wall Street Journal reviews Ending Aging: The Rejuvenation Breakthroughs That Could Reverse Human Aging in Our Lifetime. (If the direct link is blocked by the WSJ subscription wall, you can find a PDF version of the review in the Immortality Institute book discussion): "de Grey opens by explaining his mission: extending the human life span for hundreds of years. If there is a War on Drugs and a War on Terror, then why not a War on Aging, since these days aging kills just about everyone? This idea, he says, draws irrational objections from otherwise smart people. Many believe that aging is not a disease but an inescapable aspect of life, programmed into our bodies. Readers who make it through the book's geeky midsection will come away with a workable understanding of [de Grey's] provocative view: Old age may be only the consequence of lax biological housecleaning. ... He thinks more like an engineer than a scientist: Never mind how the body works, can we fix it to keep it running longer? In the book's final section, he decries the misplaced priorities that have hindered this kind of anti-aging research: Scientists can get millions of dollars to seek cures for Alzheimer's disease that afflicts the elderly, but hardly anyone gets paid to figure out how to keep people from growing old in the first place. Part of the problem is a complacent adherence to the status quo, [de Grey] says, but he also thinks that scientists are afraid to encourage a revolutionary initiative such as rejuvenative biotech research."

Link: http://online.wsj.com/article/SB118919946556720937.html?mod=googlenews_wsj

Talking With Caleb Finch
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The Daily Herald interviews gerontologist Caleb Finch: "In the last 200 years, one year of extra lifespan has been added for about every four years of historical time. Life expectancy has doubled since the industrial revolution, from about 40 years to near 80 years. ... Longer lifespans have been a worldwide phenomenon associated with improvements in hygiene and medical care and reductions in infectious disease. Some have explained this through the reduction of infant mortality. But we're also living longer because we're staying healthier -- kids have fewer infectious diseases to fight with. This reduction of inflammation and infection, along with the improvement of nutrition, has contributed to longevity by slowing many of the diseases of aging. ... It's by no means certain that the life span increases of the last 200 years will continue at the same rate or be available to all people. My own hunch is that life span could increase considerably more, but it may depend on finances and access to top-level medical resources." The conservative public positions of mainstream gerontology are slowly being drawn closer to a more sensible outlook - that we can do a great deal to extend human life span in the next few decades, and we should get working on that right away.

Link: http://www.dailyherald.com/story/?id=33274

The Active Field of Tissue Engineering
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In order to replace age-damage tissue, the medical community must develop the skills and infrastructure to reliably form new, undamaged organs from our own cells and grow tissue to order in situ, inside our bodies. The field of tissue engineering is enjoying the benefits of funding, understanding and widespread support at the present time; research communities are rife with innovation and progress, and practical application of the underlying science is moving rapidly. A few examples of present lines of research:

Stem cells for tissue engineering of articular cartilage:

Tissue engineering is a recently developed science that merges the fields of cell biology, engineering, material science, and surgery to regenerate new functional tissue. Three critical components in tissue engineering of cartilage are as follows: first, sufficient cell numbers within the defect, such as chondrocytes or multipotent stem cells capable of differentiating into chondrocytes; second, access to growth and differentiation factors that modulate these cells to differentiate through the chondrogenic lineage; third, a cell carrier or matrix that fills the defect, delivers the appropriate cells, and supports cell proliferation and differentiation.

Stem Cells In Tendons That Regenerate Tissue Identified In Animal Model:

Clinically, tendon injury is a difficult one to treat, not only for athletes but for patients who suffer from tendinopathy such as tendon rupture or ectopic ossification. This research demonstrates that we can use stem cells to repair tendons. We now know how to collect them from tissue and how to control their formation into tendon cells.

Design of Tissue Engineering Scaffolds as Delivery Devices for Mechanical and Mechanically Modulated Signals:

Defining tissue template specifications to mimic the environment of the condensed mesenchyme during development allows for exploitation of tissue scaffolds as delivery devices for extrinsic cues, including biochemical and mechanical signals, to drive the fate of mesenchymal stem cells seeded within. ... As the range of mechanical signals conducive to guiding cell fate in situ is further elucidated, these refined design criteria can be integrated into the general optimization rubric, providing a technological platform to exploit nature's endogenous tissue engineering strategies for targeted tissue generation in the lab or the clinic.

Concepts of scaffold-based tissue engineering-the rationale to use solid free-form fabrication techniques

A paradigm shift is taking place in orthopaedic and reconstructive surgery from using medical devices and tissue grafts to a tissue engineering approach that uses biodegradable scaffolds combined with cells or biological molecules to repair and/or regenerate tissues. One of the potential benefits offered by solid free-form fabrication technology (SFF) is the ability to create scaffolds with highly reproducible architecture and compositional variation across the entire scaffold, due to its tightly controlled computer-driven fabrication.

Reconstruction of functional tissues with cell sheet engineering:

We have developed an approach that uses culture surfaces grafted with the temperature-responsive polymer [that] allows for controlled attachment and detachment of living cells via simple temperature changes. Using cultured cell sheets harvested from temperature-responsive surfaces, we have established cell sheet engineering to create functional tissue sheets to treat a wide range of diseases from corneal dysfunction to esophageal cancer, tracheal resection, and cardiac failure. Additionally, by exploiting the unique ability of cell sheets to generate three-dimensional tissues composed of only cultured cells and their deposited extracellular matrix, we have also developed methods to create thick vascularized tissues as well as organ-like systems for the heart and liver.

Building anything is "just" a matter of moving the right molecules to the right place - today a matter of understanding how to put blood vessels into grown segments of heart tissue, tomorrow building a complete kidney from scratch, nanostructures all complete and in the right place. Present trends in biotechnology and other branches of applied science see us becoming ever better at these tasks in the years ahead. Remember that medicine is a form of engineering; the repair, refit and replacement of biological systems is one important path to the future of longer, healthier lives.

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Aging, Ghrelin and the Thymus
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Calorie restriction practitioners might find this piece from EurekAlert! (and the accompanying full text PDF) interesting: "The deterioration in immune function that occurs as an individual ages is thought to occur because the thymus involutes with age, causing a dramatic decrease in T cell output. New data [suggest] that in mice, thymic involution is caused by a decrease upon aging in thymic expression of both a hormone that is better known as a stimulator of food intake (ghrelin) and its receptor. ... harnessing this pathway might provide a new approach to boost immune function in individuals who are elderly or immunocompromised. ... infusion of ghrelin into old, but not young, mice markedly increased thymic mass, improved thymic architecture, and increased thymocyte and thymic epithelial cell numbers. These changes were associated with increased T cell output and increased diversity of the TCR repertoire of the peripheral T cell population. Consistent with these observations, age-associated thymic involution was accelerated in mice lacking either ghrelin or its receptor." It's far too early to be suggesting connections between the increased release of ghrelin with hunger and positive effects over the years of being hungry more often, but it is an intriguing line of thought.

Link: http://www.eurekalert.org/pub_releases/2007-09/joci-hhf083007.php

Towards 1,000 Year Life Expectancies
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The Times Online looks at the work of Aubrey de Grey: "Dr de Grey is trying to end human ageing. End it, or, as he describes his mission, 'to engineer huge gains in human life span'. Huge gains as in a 1,000-year life span, and a healthy 1,000 years at that. Huge gains as in the reversal of ageing in those already considered old. Huge gains as in the end of cancer, heart disease, stroke, diabetes and Alzheimer's. ... People really go into a sort of pro-ageing trance when you start talking about radically extending life. It's as if they'd rather defend something they think they know – that life span is finite – than deal with ageing itself as a disease and as something to be defeated. Isn't that amazing? Can you believe it? ... He has just published a book, Ending Aging, which has earned good marks from some of his peers. He is constantly on the road, speaking far and wide to large audiences. This week he is holding his third conference on what he calls SENS, or 'strategically engineered negligible senescence', in Cambridge; it will be attended by some of the leading lights of modern gerontology, pathology and cell biology. ... Last year Peter Thiel, the American founder of PayPal, the money transfer service, committed himself to a $3 million matching donation. The Methuselah Prize, that de Grey started a few years ago to reward anyone who could double the life span of a laboratory mouse, now stands at $4.4 million."

Link: http://www.timesonline.co.uk/tol/life_and_style/health/features/article2400692.ece

Glancing at Ongoing Resveratrol Research
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The Annals of the New York Academy of Science has a paper in preprint (abstract and full PDF) on the mechanisms by which resveratrol might induce health and longevity benefits similar to those of calorie restriction in mammals. In particular, this research suggests that resveratrol doesn't act directly through sirtuins, such as SIRT1:

The natural polyphenol resveratrol stimulates sirtuins and extends lifespan. Here resveratrol inhibited expression of replicative senescence marker INK4a in human dermal fibroblasts and 47 out of 19,000 genes from microarray experiments were differentially expressed. These included genes for growth, cell division, cell signaling, apoptosis and transcription. Genes involved in Ras and ubiquitin pathways, Ras-GRF1, RAC3 and UBE2D3, were downregulated. The changes suggest resveratrol might alter sirtuin-regulated downstream pathways, rather than sirtuin activity. Serum deprivation and high confluency caused nuclear translocation of the SIRT1-regulated transcription factor FOXO3a. Our data indicate resveratrol's actions might cause FOXO recruitment to the nucleus.

...

we propose that resveratrol does not allosterically activate SIRT1, but rather stimulates interaction of SIRT1 with FOXO3a by inducing FOXO3a nuclear localization through the downregulation of Ras activity. Therefore, an increase in FOXO3a transcriptional activity by resveratrol might quickly decrease cellular damage, so leading to a decrease in INK4a expression, and consequently attenuate replicative senescence. Given that INK4a is induced by Ras overexpression as a tumor-suppressor mechanism the decrease in INK4a expression would be due directly to a reduction in Ras pathway activity.

Chronic resveratrol treatment did not increase the time required to reach replicative senescence, despite likely beneficial effects of resveratrol in reducing cellular damage, as judged by the reduction in INK4a it induced. On the other hand, reduced cellular p16ink4a should have a favorable effect on physiological function at the organismal level, unrelated to its effect on lifespan of fibroblasts. Effects on other cell types could, moreover, be quite different.

It's a good indicator of the complexity of metabolism: this tiny part of the whole is a dynamic dance of many different mechanisms, all feeding back into one another, their interactions poorly understood at this time. I give it another five to ten years before the scientific community has enough of calorie restriction biology nailed down to the point of being able to safely, knowingly manipulate it by means other than food intake.

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Pictures From the Three Hundred Dinner
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Members of the Methuselah Foundation's Three Hundred, generous donors and forward-looking philanthropists all, gathered for their second dinner on the evening before the SENS 3 conference. You'll find pictures at the Methuselah Foundation blog: "I'm told a good time was had by all. David Chambers, Foundation COO, smuggled out some pictures of the event: here they are, capturing our generous donors, Foundation volunteers, a good dinner and numerous signed copies of Ending Aging." The book on the Strategies for Engineered Negligible Senescence (SENS) we've all been waiting for is out, the SENS 3 conference on rejuvenation science and the repair of aging is underway, and the Methuselah Foundation moves from strength to strength thanks to the many volunteers and donors who continue to step forward. Good times - we're making real progress along this first leg of the road to building a scientific community with the will and resources to seriously tackle degenerative aging. It's hard work, but it's happening.

Link: http://blog.methuselahfoundation.org/2007/09/at_the_three_hundred_member_di.html

Cartilage From Embryonic Stem Cells
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EurekAlert! reports on continued progress in generating new cartilage to replace damaged or age-worn tissue: "Because native cartilage is unable to heal itself, researchers have long looked for ways to grow replacement cartilage in the lab that could be used to surgically repair injuries. This research offers a novel approach for producing cartilage-like cells from embryonic stem cells ... Using a series of stimuli, the researchers developed a method of converting the stem cells into cartilage cells. Building upon this work, the researchers then developed a process for using the cartilage cells to make cartilage tissue. The results show that cartilages can be generated that mimic the different types of cartilage found in the human body, such as hyaline articular cartilage -- the type of cartilage found in all joints -- and fibrocartilage -- a type found in the knee meniscus and the jaw joint. Athanasiou said the results are exciting, as they suggest that similar methods may be used to convert the stem cell-derived cartilage cells into robust cartilage sections that can be of clinical usefulness."

Link: http://www.eurekalert.org/pub_releases/2007-09/ru-esc090607.php

Ending Aging Around the Blogosphere
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A few reactions to the newly published "Ending Aging: The Rejuvenation Breakthroughs That Could Reverse Human Aging in Our Lifetime" for you today, starting with a thoughtful post from ShrinkWrapped:

two things struck me about these exceptional men (and a few women of science) to whom we owe so much. One was their passionate dedication to understanding the world around them. ... The second thing that struck me and stayed with me was how fleeting their time was. ... all these men, even Galileo who lived to be 78, died at an age that nowadays we would consider far too young.

...

[Aubrey] de Grey does an excellent job of making the research, which can seem (and is) exceptionally complex, understandable and approachable. But here is his key insight: there is nothing about these problems that is resistant to understanding and remediation given enough scientific time, energy, and money. In other words, researchers are already working on the problems (although often without explicitly working on "curing" aging) and none of the problems appear to be impossible to solve!

There is a very human desire to minimize disappointment. Almost everyone at one time or another has fantasized about living forever. Human beings from time immemorial have searched for the Fountain of Youth. To imagine we could actually be approaching such a resolution would be too painful for many; the possibility would be rejected as preferable to having hopes dashed. Yet by building on the life's work of the brilliant and persistent men and women of the last 500 years, we are indeed approaching the threshold of astounding advances in all areas of information technology and biology is increasingly becoming an information science.

...

it occurred to me that all of these great men and women who came before me died too soon, their work unfinished. I suspect most of us, even now the beneficiaries of anti-aging science (after all, what are anti-hypertensives and statins, if not anti-aging medications) do not wish to suffer the same way. No one wants to die with their work here unfinished.

Very true. The search for longevity is the quest to give people a choice presently lacking - to live another day, and take on the next challenge, should you so desire. Aging is no different than any other limit imposed upon us by the accidents of fate and evolution: we will overcome it, as we have overcome so many other limitations of the human condition of ages past, and remember the tragedy of those who had to live and die before that milestone was achieved.

Moving on, I'm pleased to note that the folk at the Speculist are enjoying their copies:

Phil got his hands on an advanced copy and has promised a review. ... This is the book that those of us who have followed life extension closely have been eagerly awaiting.


...

You must get this book.

Economist Arnold Kling is threatening a review:

I just finished Aubrey de Grey's Ending Aging. I think that anyone who likes reading science books for pleasure would enjoy it. I'll have more to say later.

Finally, a piece on Aubrey de Grey and Ending Aging from the Daily Galaxy:

Like Francis Bacon, de Grey has never stationed himself at a laboratory bench to attempt a ­single hands-on experiment, at least not in human biology. He is a computer scientist who has taught himself natural science, and has set himself toward the goal of transforming the basis of what it means to be human.

Dr. de Grey, who holds a rare University of Cambridge degree on this basis of publications rather than classwork, believes that the key biomedical technology required to eliminate aging-derived debilitation and death entirely is now within reach - technology that would not only slow but periodically reverse age-related physiological decay, leaving us biologically young into an indefinite future.

De Grey is an administrative and theoretical scientist; he has formulated the Strategies for Engineered Negligible Senesence, published extensively in scientific journals, is editor-in-chief for for the journal Rejuvenation Research, speaks at conferences around the world, and presently directs research aimed at repairing aging through the Methuselah Foundation and in collaborative work with biomedical researchers. More pertinently, he is the epitome of direct action: starting from scratch, he has made himself into a force for change in aging research and, by extension, all our futures.

Get out there and buy the book in which Aubrey de Grey and Michael Rae explain, as best we know based on the biotechnology and scientific knowledge of today, how we can band together, build a mighty research infrastructure, and greatly extend our healthy life spans soon enough to matter.

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The Consensus on Aging and Cancer
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A high level review of the consensus position on the dynamic, evolutionary relationship between aging and cancer: "Ageing is due to the accumulation of damage, which arises because of evolved limitations in mechanisms for maintenance and repair. Accumulated damage may cause genomic instability, which in organisms with renewable tissues may result in cancer. To keep cancer at bay, two different tumour suppression mechanisms evolved: caretakers and gatekeepers. Caretakers protect the genome against mutations, while gatekeepers induce cell death or cell cycle arrest of potentially tumourigenic cells. It has been hypothesised that decreased activity of a caretaker may reduce life span, by increasing cancer risk, while the effects of increased activity of a gatekeeper on cancer risk and life span may be antagonistically pleiotropic. Apoptosis and senescence will promote early-life survival by curtailing the development of cancer, but may eventually limit longevity. This article reviews the evidence for this hypothesis. We conclude that several different findings indeed hint at an important role for gatekeeper mediated processes in ageing and its related pathologies. The relative contribution of apoptosis and senescence in specific age-related pathologies remains to be established."

Link: http://www.ncbi.nlm.nih.gov/pubmed/17764928

More Opinions On Calorie Restriction Longevity
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Everyone's willing to hazard an estimate on the longevity induced by the practice of calorie restriction these days, it seems. The Advertiser interviews one of the scientists behind a paper I noted recently: "Calorie restriction prolongs life. There's no question about this effect. That is true in the rat and it's also true in the mouse. In a human it's another matter. Human beings can live to 100 years so you have to run a longer study ... a range of shorter studies on humans [show] calorie reduction leads to a reduction in risk factors for major killer diseases .. One study showed that if there are no risk factors for cardiovascular disease and diabetes when a man is 50, then 55 per cent of those men will live to 85. Another showed that if no risk factors are present at 50, 65 per cent of women and 50 per cent of men will live to 85. Based on these and other studies, Dr Everitt estimates lifelong calorie reduction would extend life by between five and 10 years." The studies strongly suggest that extended life would be much healthier, on average.

Link: http://www.news.com.au/adelaidenow/story/0,22606,22369321-2682,00.html

Pointing Out the People Database Project Blog
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I linked to a transcript of an Aubrey de Grey presentation at the People Database project blog a few days ago, but I feel I should direct your attention to the whole rather than pieces. The blog is one of the Accelerating Future initiatives, and author Jeriaska is doing a great job in pulling together video and transcripts of noteworthy transhumanist advocates, entrepreneurs and activists. Amongst those people are ardent supporters of healthy life extension research, folk working hard to advance medical science and grow the funding pool for serious attempts to repair aging. A couple of examples from the People Database project blog:

Both names well known to readers here, I don't doubt. Surrounding those are posts on experts and advocates for the development of artificial intelligence, molecular manufacturing, and other transformative technologies to help liberate us from the confines of the human condition as it presently exists.

All in all a worthwhile and useful resource. Go and take a look.

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Taking Cancer Seriously Enough to Really Cure It
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I'd missed the second Google presentation given by Aubrey de Grey this year, entitled "WILT: taking cancer seriously enough to really cure it." Here, Russell Whitaker points us in the right direction: "Eight weeks ago, I hosted Dr. Aubrey de Grey for his second talk at Google in Mountain View, California, a follow-up to his earlier Google talk in the SENS series ... The intrinsic genetic instability of cancer cells makes age-related cancers harder to postpone or treat than any other aspect of aging. Any therapy that a cancer can resist by activating or inactivating specific genes is unlikely to succeed long-term, because pre-existing cancer cells with the necessary gene expression pattern will withstand the therapy and proliferate. WILT (Whole-body Interdiction of Lengthening of Telomeres) seeks to pre-empt this problem by deleting from as many of our cells as possible the genes needed for telomere elongation. Cancers lacking these genes can never reach a life-threatening stage by altering gene expression, only by acquiring new genes, which is far more unlikely. Continuously-renewing tissues can be maintained by periodic reseeding with telomere elongation-incompetent stem cells that have had their telomeres lengthened in vitro with exogenous telomerase. I will describe why WILT may become a uniquely comprehensive anti-cancer modality, and the practicalities of performing it and avoiding side-effects."

Link: http://www.survivalarts.com/archives/001445.html

From Around the Web
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As I'm sure you all noticed, Ending Aging is launched and heading for the shelves - get thee hence and get a copy if you haven't already. If you'd like to learn more about the research funded by the Methuselah Foundation, and a realistic basis for radical life extension, then this is the book for you.

Meanwhile, at the "but what can I do now?" end of the spectrum, CBS ran a piece on calorie restriction (CR) today - hauling out the obligatory dietician ignorant of the science behind CR to act as the "balance" in the article. Journalism 101: find someone, anyone, who has a contrary opinion to the main thrust of the article. That this is standard practice is a great argument for the ongoing decentralization of media; let the people who are knowledgeable talk about their fields, should they be so inclined.

Restricting calories in laboratory animals has been shown to affect cell behavior that may be involved in age-related diseases such as Alzheimer's, heart disease, and cancer, Senay points out. What's more, it's been shown to increase lifespan: Mice lived 30 percent longer than usual on calorie-restricted diets.

But dietician Elisa Zied, a spokesperson for the American Dietetic Association, says Calorie Restriction is too severe, and the animal research can't easily be translated to humans' health.

Notes Zied, "We have no clinical data in humans to supports calorie restriction to have all these benefits. So, I think people really need to read between the lines, and I don't think, in our lifetime, we're ever going to really see that Calorie Restriction is the fountain of youth."

"No clinical data" is nonsense, of course - there's more than enough of it to be going on with. A fair number of research groups are running human studies, and have been publishing results for years. Check out the links on the Longevity Meme calorie restriction page for starters - like this one from 2004:

It's very clear that calorie restriction has a powerful, protective effect against diseases associated with aging.

Moving on, FuturePundit notices a good example of scientific optimism on timelines for regenerative medicine: I can't imagine that this particular instance takes regulatory barriers into account.

British scientist Simon Hoeurstrup and heart surgeon Magdi Yacoub claim that in 3 to 5 years they will be able to grow replacement heart valves from a patient's own bone marrow stem cells.

Lastly, with the SENS3 conference on healthy life extension research right around the corner, researcher Attila Chordash picks out his favored presentations to attend:

John Schloendorn is one out of the new wave of researchers and life scientists who can perfectly fit their scientific drive and skills with his serious life extension commitment. In fact, I dare to say that John would not be involved in life sciences if he did not have the chance to explore a healthy life extension technology.

...

Medical bioremediation is the proposal to utilize the catabolic diversity of environmental microbes to treat all conditions associated to catabolic insufficiency in aging humans. Here we report on our progress towards medical bioremediation. We have isolated several bacteria degrading 7-ketocholesterol and other oxysterols implicated in atherosclerosis. We also present a method to determine the early steps in the biochemical pathway of 7-ketocholesterol degradation, which may be used to screen different species for therapeutically interesting reactions. We have also recently begun work on other targets, such as lipofuscin components and advanced glycation end-products.

Bioremediation will be a growth field in the years ahead; the opportunities are self-evident. The ability to safely degrade compounds involved in age-related degeneration will be a very big deal indeed, is eminently plausible, and merits far greater funding than exists at present.

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"Ending Aging" Published Today
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As noted at KurzweilAI.net: "Aubrey de Grey's much-anticipated book, Ending Aging: The Rejuvenation Breakthroughs That Could Reverse Human Aging in Our Lifetime, co-authored by Michael Rae, was published today by St. Martin's Press. Dr. de Grey believes that the key biomedical technology required to eliminate aging-derived debilitation and death entirely - technology that would not only slow but periodically reverse age-related physiological decay, leaving us biologically young into an indefinite future - is now within reach. The authors explain that the aging of the human body, just like the aging of man-made machines, results from an accumulation of various types of damage. As with man-made machines, this damage can periodically be repaired, leading to indefinite extension of the machine's fully functional lifetime, just as is routinely done with classic cars. We already know what types of damage accumulate in the human body, and we are moving rapidly toward the comprehensive development of technologies to remove that damage. By demystifying aging and its postponement for the nonspecialist reader, de Grey and Rae systematically dismantle the fatalist presumption that aging will forever defeat the efforts of medical science."

Link: http://www.kurzweilai.net/news/frame.html?main=/news/news_single.html?id%3D7212

Predicting Vanishment For the Tithonus Error
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This short article on corporate strategy has been circulating over the past couple of days; I found it interesting:

Campbell Soup Company is expecting a major shift in the market, which will affect the way products are developed and marketed.

According to Chor San Khoo, the firm's vice president of global nutrition and health, longevity will be the next big trend to hit the industry.

"Wellness is a huge market, and is growing at double digit rates. But the way consumers consider wellness is changing, and we predict there will be great changes in the market over the next ten years, which will impact how we develop products, how we market them, and possibly how we regulate them," she said.

"When the health and wellness market first emerged, the focus was on foods with health benefits. Now it is on a better quality of life. In the future, consumers will want to live longer."

According to Khoo, the major factors affecting the health and wellness market are an ageing population, increasing obesity, nutrition individualization, and higher numbers of working women.

"We're getting older and fatter. Obesity is the cross point to multiple disease conditions. In the next ten years, I predict we won't use the term 'wellness' anymore, we'll use 'live longer' as a basis for how we market products," she said.

As I've no doubt mentioned once or twice, the best way to cut through the blather and see what people really think about the future is to listen to those who (a) have have money at stake, and (b) are accountable for failure. That isn't to say that individuals or factions within that group will be right, but the wisdom of this crowd is the best you're likely to find.

What is most interesting to me here is not that you'll find people who care deeply about perceptions of health and life span at the Campbell Soup Company - you'll find them in any large company that addresses health markets - but the belief that the Tithonus Error will vanish. It would be a sea change indeed for the person on the street in 2017 to hear "live longer" in the same way as "wellness" is heard today: a wholly beneficial term, with the accepted, implicit and internalized assumption that those extra years of life are vigorous and healthy.

This is an interesting experiment: find any random person you know and ask them what the downside would be to using better medicine to live for 150 years. Nine times out of ten, I'll wager, your friend will tell you that living for so long would be terrible because a person would spend most of his or her life decrepit, increasingly crippled by age-related conditions. In otherwords, your random friend thinks that "healthy life extension" means "being aged for longer."

This preconception about the way in which healthy life extension works is known as the Tithonus Error. It is widespread to the point of ubiquity, unfortunately. Most people dismiss healthy life extension out of hand precisely because they see no attraction in being - as they assume - increasingly aged and debilitated.

The Tithonus Error is one of a number of significant hurdles to attaining widespread support for longevity research. I'd be pleased to see the messaging resources of corporate giants working to overturn this mistaken belief in the course of doing business.

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SENS As Precursor to Cryonic Revival
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Here's a transcript of a talk given last year by Aubrey de Grey on SENS, cryonics and selling the ideas, put together at the People Database project blog: "It seems to me that the technical feasibility of cryonics is hard to sell, because real people out there don't like arguments along the lines of 'It doesn't matter how hard it is, because we've got arbitrarily long.' ... Not for any good reason, you understand. Arguments involving small numbers like '2+2=4' are altogether more effective it seems. ... Ultimately we are talking about four different concepts here: rejuvenating the body, rejuvenating the brain, reviving the body from cryostasis, and reviving the brain from cryostasis. If rejuvenating the body isn't much harder than rejuvenating the brain, then that probably means that we can get from reviving the body from cryostasis to reviving the brain from cryostasis. The difference in difficulty there will be similar. If we can get from rejuvenation, the sort of thing that I work on, keeping people's organs going by maintenance when they're still functioning to reviving those organs from cryostasis, if that's not a terribly big leap, then perhaps it can be done for the brain. ... Similarly, if cryobiology is a legitimate, even admirable field, including cryopreservation and resuscitation of organs, then we shouldn't really have too much difficulty in believing that cryonics is technically feasible in the foreseeable future. I find that this argument works rather well."

Link: http://www.acceleratingfuture.com/people-blog/?p=130

Calorie Restriction at SFGate
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SFGate interviews calorie restriction (CR) practitioners and looks at the science behind CR: "Some of the first willing research subjects were volunteers from the Calorie Restriction Society, who in 2002 offered themselves as subjects for an ongoing study at Washington University School of Medicine. Researchers there have measured markers of health and aging, and their findings, published by the National Academies of Sciences in 2002, say CR led to 'profound and sustained beneficial effects.' These included lowered cholesterol and blood pressure, less body fat and reduced levels of a protein known to cause inflammation, which is believed to be a factor in diseases. ... We used to be considered a bunch of extremist wackos who were starving ourselves to live longer. But now most any major university that does research is doing some on CR ... My friends that I have coffee with in the morning, one has three or four stents in him and has diabetes. Another one has two or three stents and has gout. They are in their late 50s and early 60s and they shouldn't be having these troubles. They watch me every day and they can see the price they are paying."

Link: http://www.sfgate.com/cgi-bin/article.cgi?f=/c/a/2007/09/02/CM0CRASBE.DTL