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.

Technorati tags: economics, life extension

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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.

Technorati tags: aging, inflammation, medical research

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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.

Technorati tags: activism, book, 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.

Technorati tags: life extension

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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.

Technorati tags: cancer research

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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.

Technorati tags: libertarian, medical research, politics

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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.

Technorati tags: aging, biochemistry, medical research

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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.

Technorati tags: conference, life extension, SENS

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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.

Technorati tags: aging, longevity

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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.

Technorati tags: life extension, media, science

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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.

Technorati tags: life expectancy, life extension

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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.

Technorati tags: gerontology, journal, science

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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.

Technorati tags: aging, gerontology, science

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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.

Technorati tags: biotechnology, xenotransplantation

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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.

Technorati tags: biotechnology, tissue engineering

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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.

Technorati tags: calorie restriction, medical research, resveratrol

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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.

Technorati tags: aging, life extension, science, SENS

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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:

• Aubrey de Grey
• Robert Frietas

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.

Technorati tags: life extension, transhumanism

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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.

Technorati tags: life extension, science

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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.

Technorati tags: advocacy, life extension

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