A number of interesting new directions in Alzheimer's research have been emerging over the past few years. There's the choroid plexus connection, and the possibility of repairing the normal mechanisms of amyloid removal, for one. It turns out that amyloid creation and removal are actually very rapid, dynamic processes, and the buildup towards Alzheimer's is a slowly growing imbalance between ongoing creation and removal. Also, the realization that Alzheimer's looks an awful lot like type 2 diabetes at a biochemical level, with all the same lifestyle risk factors relating to exercise, eating and visceral fat. Lastly for this list, there is some form of biochemical connection between Alzheimer's and the inflammatory immune response.

Chronic inflammation crops up everywhere you look in the pathology of aging, and as a risk factor for all the common age-related diseases. More chronic inflammation isn't a good thing, but an age-damaged immune system will give you more of it whether you want it or not. Excess visceral fat will add even more inflammation on top of that.

The latest Alzheimer's science to catch my eye springs from research into inflammation and amyloid plaques, but turns up a result that looks a lot like immune therapy:

Earlier studies had shown that Alzheimer's patients tend to have elevated amounts of TGF-β, which plays a key role in activating immune system response to injury. Some had thought the presence of the molecule was simply an attempt to quiet the inflammatory response caused by a buildup of plaque.

Instead, the team found that as much as 90 percent of the plaques were eliminated from the brains of mice genetically engineered to block TGF-β in the peripheral immune cells.

...

Amyloid plaques are thought to damage brain nerve cells (neurons) and stimulate a response in nearby inflammatory cells called microglia. Theoretically, Alzheimer's might be treated by somehow preventing or removing the plaque buildup and calming the inflammation.

...

When TGF-β was blocked, the immune system seemed to unleash immune cells known as peripheral macrophages. The macrophages passed through the blood-brain barrier and surrounded the neurons and plaques in the brains of mice. "If results from our study in mice engineered to develop Alzheimer's-like dementia are supported by studies in humans, we may be able to develop a drug that could be introduced into the bloodstream to cause peripheral immune cells to target the amyloid plaques."

This wasn't the result researchers were expecting when they engineered these mice. So much of progress comes about through unintentional discoveries in the course of sensible exploration.

Posted by Reason at 6:47 PM
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Aschwin de Wolf continues to republish important writing from the early days of the modern healthy life extension community at Depressed Metabolism. Those were the years of the late 1960s, in which the seeds were laid for the cryonics community on the one hand and pro-longevity supplement and "anti-aging" groups on the other. There's really a deep divide between the two factions in terms of fundamental philosophy: on the one hand aiming a few more years (or decades, as they overoptimistically thought at the time) of healthy life via applied pharmacology, on the other the engineer's path to defeating death completely. Quite different worlds of ambition - and as it turned out, rationality. The cryonicists, with visions of immortality in their sights, were far more correct about the bounds of the possible, given scientific knowledge at the time.

Once vitrified and stored at low temperature, a cryopreserved individual has time and the astounding curve of scientific progress on his side. The laws of physics and our present understanding of brain biochemistry place no obstacles in the path of restoring cryopreserved people - it's a matter of developing the necessary medical technology, and remaining well-stored until that time comes to pass.

Now "immortality" is a much abused term, cast widely and with many colloquial meanings. Linguistic drift has come to put it somewhere between "long-lived" and "ageless but vulnerable to accident" in all but more precisely spoken communities. But it was much used by the early cryonicists in a way closer to the dictionary definition, and that more than anything else I think captures their excitement at having envisioned the scientific doorway out of the trap - a tool that could provide a possible way around death. For example, the early cryonics book "Immortality: Physically, Scientifically, Now" by Ev Cooper, subtitled "A reasonable guarantee of bodily preservation, a general discussion, and research targets":

Though few, if any, cryonicists today can retrace their personal interest in cryonics to Ev Cooper, and despite the broader recognition of Robert Ettinger’s later-published work, “The Prospect of Immortality,” Ev Cooper’s privately published 1962 manuscript, “Immortality: Physically, Scientifically, Now,” represents the first major treatise on what would later become known as cryonics. Soon afterward Ev also started the first cryonics organization, the Life Extension Society (LES), from which several other cryonics societies eventually emerged.

...

A handful of prophets: H. G. Wells, G. B. Shaw, Jules Verne, Capek, and Tsiolkovsky made some startlingly accurate predictions in the late 19th and early 20th centuries. The more sober members of mankind never held to them seriously, neither then nor now, passing them off as the successes amongst the law of chance. No matter how it came about - and some of these men were of acute scientific understanding and broad perspective - many of the possibilities they spoke of did come to pass: rocket travel, atomic energy, automatons that work in offices and run factories - too many to list.

Now in the last half of the 20th century, to take seriously that physical immortality, here on earth, is scientifically possible is almost as much as dream can encompass, certainly more than sobriety can allow. This is perhaps a necessity, for it is only more absurd to chase after every South Sea bubble. And, ever since prehistoric man first imagined the possibility of life forever, the countless rolling centuries have not given him one shred of material verifiable evidence. Now, however, when some of the scientific possibilities appear on the horizon, someone has to form the question, consider a reversal of the skepticism engendered by centuries of disappointment and prepare the way for the reality of the incredible.

Why was cryonics envisaged as the step directly to immortality? Because, should the plausible outline of the process work, it is a gate to the future of far more capable technology. A future after the biotech revolution, in which our biochemistry does our bidding, aging can be repaired, and molecular manufacturing is in full swing. An age of bioartificial bodies, minds transferred to new and more robust mechanisms, strong artificial intelligences, and indeed, anything you might imagine that the laws of physics permit and enough time has passed to develop.

I'm not going to try to convince you that the future will be a golden, wondrous place: either you accept the implications of the present rate of progress towards what the laws of physics make possible, in which case you've probably thought this all through at some point, or you don't. Life, space travel, AI, the building blocks of matter: we'll have made large inroads into bending it all to our will within another half century. Many of us will live to see it even without the benefits of medical technology to come: growing up in a 1970s urban area will be the new 1900s farmboy youth come 2040; a strange and primitive near-past erased by progress, for all that so many people still alive actually lived it, time travellers in their own lifetimes.

In any case, I think it's interesting to ponder why cryonics is no longer seen quite so stridently as the gate to immortality, despite the fact that cryonics technology has advanced steadily since the 1960s, as has our understanding of our brain's biochemistry. Could it be because that the horizon for successful restoration has pulled in - perhaps as early as the 2040s? Cryonics advocates no longer expect to be restored to a time massively different to our own, because the journey will likely be one of decades rather than centuries.

The vision of immortality can still be conjured just as stridently, should we so wish, but it's somewhat fashionable at the moment to distance oneself from talking about immortality. There are practical aspects too. Now that we have serious, scientific work taking place aimed at the repair of aging, and fundraising for faster progress is an earnest endeavor, one can't afford to be throwing around words that can be easily misconstrued. The path to moderation of the vision is hard to avoid once money starts flowing in.

I started on the path that led to the Longevity Meme and Fight Aging! from the position that immortality was a good thing, and knowing that the laws of physics did not disallow a damn good attempt at actual immortality - the "no death, ever" dictionary definition - or at least a life span of millions of years on the way to that end goal. If that's not long enough to figure out the aspects of the problem that cannot be answered today, I'm not sure what would be. If I'd been born two decades earlier, I'd have been a cryonics advocate and volunteer. As it is, it looks like these first decades of the 21st century are the era in which step one (of thousands, no doubt) of simply remaining alive forever - continuously repairing aging in these bodies of ours - can be achieved.

A philosophy of first things first is a good way to temper visions of steps two through however many thousand, and explains why I spend my time talking about the Strategies for Engineered Negligible Senescence and the biotechnology revolution. If we don't complete the first step, sufficient control over our biochemistry to repair aging, then it's all for nothing.

So, the million year life span: how could that be achieved? The short, and not terribly informative answer is that you get it done by using advancing technology to dramatically reduce your vulnerability to fatal accidents, murder, and the like. If you project out the accident rates for life today, you'll see that an ageless human, sustained by forseeable biotechnologies of cellular and biochemical repair, has a life expectancy in the 1000 to 5000 year range. Sooner or later that piano is going to fall on you hard enough that even advanced medical technology can't fix you up.

Once you start looking at living for 100,000 years in much the same shape as you are today, it becomes apparent that almost any activity bears a level of risk that'll jump up and kill you. Eating, swimming, reading ... breathing. Stretch out the time for long enough and the improbable and fatal will happen to you.

The answer is to change the shape you are. Getting past step one, the repair of aging, gives you a few hundred years of comparative statistical safety. I can't imagine that much of the technology needed for step two will remain beyond the human civilization of the 2200s. Your step two will no doubt vary, but I would get my neurons replaced (slowly, one at a time over time, to ensure continuity of the self) with some form of much more robust, easily maintained nanomachinery. That allows these sorts of engineering possibilities:

• Swapping out the body for whatever machinery of transport and support best minimizes risk
• Moving most of the business of life into simulation
• Physically separating my neurons while still remaining alive, conscious and active

It's that last point that's key, as physical locations have the same sort of issues with time, probability and bad events as people do. Meteorites happen, as do landslides, earthquakes and volcanoes. The way to reduce your risk function dramatically is to spread out. You can imagine a wireless brain (using whatever the most robust communications technology of the time happens to be be) scattered in a thousand separate locations across a continent, or the whole planet.

That should be good for 10,000 years of falling pianos of various types. However, once you start digging back into the geological and astrophysical history of the solar system, it's clear that spreading out over an entire planet still leaves you at risk on longer timescales. Probably not from impacts: I'll be surprised if we can't solve that problem within few centuries from now. There's always war, nearby supernovae, massive unexpected solar flares, and other unpleasant items, however. The supernovae are the biggest of the known concerns, given that I expect it'll be a long, long time before preventing them is a practical and ongoing business for the civilizations that follow man.

Spreading out is an option again: boost up the size of your components and neuromachinery for worst-case-scenario radiation projections, provide them with the means to move about the solar system, and become a spacefaring entity, spread out over a sizeable selection of orbits. By that point in time, your physical presence resembles a small country of nanomachinery, automation and delegation. The trade-off for spreading out and further greatly reducing your long-term risk of death is that you slow down. The speed of thought is determined by the speed of communication between neurons in components in different orbits. If your brain is light hours wide, you will live very slowly indeed - but for so long, that you come out ahead.

There are other paths forward, of course, with varying degrees of risk and invention. I haven't touched living very fast in simulation by running your brain on faster hardware, for example. The practicality and possibilities as determined by the laws of physics and what we have invented to date have been debated well over the past decades of the transhumanist community; if you head out there online to look, you'll find a wealth of fascinating material.

Is immortality impractical? Given the risk functions and uncertainty in the timeline for completing the repair of aging, it might be unlikely for most of us alive today because we won't get past step one. But it's far too early to say whether immortality, the "no death, ever" version, is actually impossible for all of us. Give it a million years and ask me again. The slope of technology and possibility is curving up ahead of us to great heights, and it'll be a wild ride either way.

Posted by Reason at 4:39 PM
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A stem cell niche is an environment within the body where a specific variety of stem cell is nurtured:

Stem-cell populations are established in 'niches' - specific anatomic locations that regulate how they participate in tissue generation, maintenance and repair. The niche saves stem cells from depletion, while protecting the host from over-exuberant stem-cell proliferation. It constitutes a basic unit of tissue physiology, integrating signals that mediate the balanced response of stem cells to the needs of organisms. Yet the niche may also induce pathologies by imposing aberrant function on stem cells or other targets. The interplay between stem cells and their niche creates the dynamic system necessary for sustaining tissues, and for the ultimate design of stem-cell therapeutics ... The simple location of stem cells is not sufficient to define a niche. The niche must have both anatomic and functional dimensions.

Niches age with the rest of your tissue, and for much the same reasons; an accumulation of a variety of types of cellular and biochemical damage. The machine gathers faults and rust over the years, and gradually moves towards serious failure.

There has been some debate over the past few years as to whether the well-known decline in function of stem cell populations with age occurs because of changes in the stem cells, or because of changes in their niches. It seems that the consensus is presently leaning towards the niche explanation:

Adult stem cells provide the basis for regeneration of aging tissue. Their dual ability for self-renewal and multilineage differentiation is controlled by direct interaction with a specific microenvironment - the so called "stem cell niche".

Hematopoietic stem cells (HSC) reside in the bone marrow. It is still under debate if HSC can rejuvenate infinitively or if they do not possess "true" self-renewal and undergo replicative senescence such as any other somatic cell. Furthermore, the question arises to what extent age-related changes in HSC are due to intrinsic factors or regulated by external stimuli. There is growing evidence, that the stem cell niche is most important for the regulation of cellular aging in adult stem cells.

It is the stem cell niche that (i) maintains HSC in a quiescent state that reduces DNA damage as well as replicative senescence, (ii) protects from radicals and toxic compounds, (iii) regulates cell intrinsic signal cascades and (iv) modulates gene expression and epigenetic modifications in HSC. Thus, the interplay with the stem cell niche controls HSC function including the aging process of the hematopoiesis.

As accumulating age-related damage causes the cells and processes of the niche to malfunction, the stem cells it supports suffer. One consequence of the dominance of the aging niche is the direction taken in order to develop the next generation of stem cell therapies. Clearly it's not enough to gain far better control over stem cells if the damaged niche then sabotages your efforts.

I believe that this will likely see the large and well-funded regenerative medicine industry start down the path of trying to rejuvenate and repair stem cell niches. I don't know when that will start in earnest, but it will be a tremendous opportunity for those of us interested in the success of more general strategies for biochemical repair throughout the body - a chance to apply large-scale funding and a large research community to specific challenges in repairing the damage of aging.

Posted by Reason at 6:24 PM
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Insulin-like growth factor 1, IGF-1, is one of a number of items of great interest for the mainstream of gerontology, those researchers focused on the workings and manipulation of metabolism. It also remains an area of uncertainty at this time, with apparently contradictory results abounding:

it has become apparent that single gene mutations in the insulin and insulin-like growth-factor signalling pathways can lengthen lifespan in worms, flies and mice, implying evolutionary conservation of mechanisms. Importantly, this research has also shown that these mutations can keep the animals healthy and disease-free for longer and can alleviate specific ageing-related pathologies. These findings are striking in view of the negative effects that disruption of these signalling pathways can also produce. ... The underscored passage brings up an issue that we've discussed here previously: Why is it that IGF-I pathway mutations can confer long healthy lives on organisms, even though supplementation with IGF-I is often quite beneficial, and depletion of IGF-I is often bad for individual organ systems? Indeed, according to another recent study, low doses of IGF-I appear to protect the mitochondria in aging rodents - why then do completely IGF-I-deficient animals enjoy extended and healthy lives?

Adding more IGF-1 in an unmodified metabolism seems to be good, but modifying metabolism to completely remove it seems to be much better. To add to these results in animals, an improved testing methodology for humans shows that more IGF-1 activity is apparently better in the elderly:

Elderly men with higher activity of the hormone IGF-1 - or insulin-growth factor 1 - appear to have greater life expectancy and reduced cardiovascular risk

...

In this study, researchers evaluated 376 healthy elderly men between the ages of 73 and 94 years. A serum sample was taken from each subject at the beginning of the study and researchers were contacted about the status of the participants over a period of eight years.

Subjects with the lowest IGF-1 function had a significantly higher mortality rate than subjects with the highest IGF-1 bioactivity. These results were especially significant in individuals who have a high risk to die from cardiovascular complications.

These new findings come as a result of a new form of testing for IGF-bioactivity. Researchers in this study used a new method, a bioassay, to measure the function of IGF-1 in the blood. Compared to commonly used methods to measure IGF-1, the IGF-1 bioassay gives more information about the actual function (bioactivity) of circulating IGF-1 in the body.

What this doesn't tell us is whether IGF-1 activity is a cart or a horse in this correlation - cause, consequence, or a little of both? I suspect that levels of IGF-1 activity are greatly influenced by obesity, metabolic syndrome, diabetes, general aerobic fitness, risk of atherosclerosis, levels of oxidative stress, and other line items of biochemical damage and poor choice that correlate with a lowered life expectancy.

So eating yourself into an early grave and hoping to dig your way out with hormone supplementation is not the way to go, as always. Neither life nor your metabolism works that way.

Posted by Reason at 6:07 PM
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Incentives matter in all areas of human endeavor. When people gather to develop and deploy new medicines, for example, they are more incentized by the prospect of personal gains - reputation, profit, feeling good by doing good, and so forth - than by the benefits brought to people they have never met. This is simple, hardwired human behavior. Exceptions are few and far between.

That we instinctively work to improve our own lot first is why progress for all happens so much faster in free, open marketplaces under the rule of law. There, everyone can trade to make themselves better off: specialization and comparative advantage means that trade benefits both sides. Trade is not zero-sum; we grow the whole pie by specializing and trading the results of our work. You go off and work to make the medicine I want, and many people like myself give some our our resources to purchase the end result. Both sides benefit, exchanging - what is for them - lesser value to receive greater value.

There is no open marketplace for medical technology in the developed world, however. Instead, we see a very different set of incentives dominating the state of research and development. Regulatory bodies like the FDA have every incentive to stop the release of new medicine: the government employees involved suffer far more from bad press for an approved medical technology than they do from the largely unexamined consequences of heavy regulation. These consequences go far beyond the obvious and announced disapproval of specific medical technologies: the far greater cost lies in all the research, innovation and development that was never undertaken because regulatory burdens ensure there would be no profit for the developer. Personal gain for the regulator is thus to destroy the gains of people they will never meet, the exact opposite of what occurs in an open marketplace.

An article that looks at one small part of the destruction caused by the FDA caught my attention, and particularly these snippets:

Since 2005 the FDA has approved 18 new cancer drugs, many of them breakthrough products. But the pipeline contains hundreds more that will never get to market because corporate developers aren't able, or willing, to come up with the money, time, and patients necessary to establish acceptable data.

...

The clinical trial process now is a three-part, years-long effort that effectively kills off all but a handful of once-promising drugs.

...

It would have been the first new drug for prostate cancer in 20 years

Twenty years! Just stop a moment and think about how far and fast biotechnology and medical science has moved in the past twenty years. Think about what the far less regulated computing industry has achieved in the same timeframe. We live in the early years of the biotechnology revolution, with something amazing and new demonstrated in laboratories every week. Yet the dominant regulatory body for one of the most advanced regions of the world has managed to stop the clock at 1988 for a major disease, the subject of research in a hundred laboratories worldwide.

This sitation exists in every field of medicine, and all participants labor under the crushing burdens imposed by regulators incentivized to stop progress from happening. The same will be true of the future of longevity medicine, unless we do something about it.

The insanity of this all is quite staggering - that people largely accept and defend the need for regulation that achieves this sort of result, that is. I have heard it said that the failure of libertarianism, of the urge to freedom and personal responsibility, is a failure of imagination on the part of those who have been brought up knowing nothing other than government and regulation on a massive scale. The majority cannot make the leap to see an unregulated marketplace for medical development that works in the same way as the unregulated marketplace for computers - enormous choice, low barriers to innovation, efficiency and low cost, competing review organizations, accountable sellers, rapid progress and responsiveness to customers driven by fierce competition, and so forth.

What is, is, and to propose another way is already an uphill battle regardless of merits. That is also hardwired into the human condition. But the present dismal state of affairs must be changed if we are to see the defeat of degenerative aging in our lifetime - nothing short of a revolution is called for, given just how far in the hole we find ourselves. The technologies needed to repair aging will take only a few decades to develop, and indeed some already exist in prototype, but the present regulatory burden placed upon medical technology will ensure we are all dead and buried, that wondrous potential squandered.

Posted by Reason at 5:13 PM
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Over at the Electric Pulse, you'll find a good introduction to the Strategies for Engineered Negligible Senescence, aimed at those folk completely unfamiliar with longevity science and the work of scientists like Aubrey de Grey:

Japanese women now have a life expectancy of 85 years. In other words, a Japanese woman who died at 82 would have passed "before her time." As a society, we’ve slowly become more accustomed to the decreasing relevance of age, whether that be Madonna dancing in cut-offs at 50, or John McCain seeking to be the oldest elected president. This societal change is a reflection of statistics. Over the past 100 years, the average American has gained two years of life expectancy every decade. This pace, however, will soon be eclipsed as science effectively ends aging. The unquestioned leader in this drive is Dr. Aubrey de Grey.

Dr. de Grey came up with SENS: Strategies for Engineering Negligible Senescence. In layman’s terms, de Grey wants to keep us from becoming frail and dying. How we get old is relatively simple and uncontroversial. As a by-product of being alive, our bodies start to build up damage, and eventually this damage causes disease.

...

The difference between us and cars is that we know everything there is to know about repairing cars. Just as a Ferrari would have been impossibly complex to build two hundred years ago, so is the body today. The difference is that biology is quickly becoming an information science. As loyal readers of this column know, information technologies increase at an exponential rate. Just like computers, biotechnology such as DNA sequencing or fMRI imaging roughly doubles in capability every year.

We will soon be able to deal with the nanoscale devices that make up the human machine and fix the damage that occur to them.

This is a great piece to send to friends and relatives who don't follow scientific progress at the Methuselah Foundation, and don't know about relevant new research out in the wider life science community - indeed, to anyone you know who doesn't spend much time thinking about aging at all. The article is simple and to the point, framing aging as the consequence of known forms of biochemical damage, presenting the best path forward as the development of therapies to repair that damage.

The biggest hurdle to the future of healthy life extension not the science, but rather that most people in the world take aging and its degenerations as writ in stone, an immutable fact of life. Only when many more folk appreciate that aging can be defeated - and defeated within our lifetimes - will we see rapid progress, large-scale funding, and the growth of a large research community to get the job done. That's something we can all help to bring about by talking more often about real science and real prospects for engineered longevity.

Posted by Reason at 8:26 PM
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Michael Anissimov is back to writing on the topic of healthy life extension once more, and a good thing too. As more writers craft works of common sense on aging and advocacy for longevity science, it becomes easier to raise significant funding for research and development aimed at repairing the damage of aging. Raising the tide of awareness to float the boats of endeavor is a labor in and of itself - but it must happen if we are to succeed.

You'll find Anissimov's latest piece hosted at the Immortality Institute:

Age-defying creams and lotions, esoteric herbs and elixirs, botox and plastic surgery, what do they all have in common?

None of them will actually increase your lifespan. Usually, they're snake oil. At best, they improve external appearance without actually extending life. We deserve better, and we'll need it if we want to live longer than the typical four score and ten years.

...

Enter Dr. Aubrey de Grey, a biogerontologist from the UK, and his "strategies for engineered negligible senescence" (SENS) plan. Instead of exclusively studying the complex biochemical processes of aging in detail, as in gerontology, or ameliorating the worst symptoms of age-related decline, as in geriatrics, de Grey and his supporters advocate an "engineering approach" to aging, which asks: what are the main categories of age-related biochemical damage, and how can we fix them? The idea is not to eliminate the sources of age-related damage, but fix the damage fast enough that it doesn't accumulate to cause health problems. This is far easier than deciphering all the intricacies of the biochemistry of aging.

Go and read the whole thing. One of the pleasant aspects of this new publishing paradigm we've engineered for ourselves on the web is that there is less of a need to forge your work, complete in every aspect, prior to presenting it. One can publish early and iterate the publication often, which I think tends to lead to a better result. In that vein, Anissimov is soliciting constructive criticism for the next iteration:

Check it out, and let me know if there’s any way it might be improved or modified.

Aging sucks! Let’s end this terrible disease, and let people live as long as they desire.

Posted by Reason at 6:56 PM
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You'll recall the arctic quahog - a species of bivalve clam - has a maximum lifespan somewhere north of 400 years. Other bivalve species fall into the 30 to 100 year range, with a fair degree of uncertainty. While you can age a bivalve by the growth rings in its shell, there are a lot of different species, and not that many people out there performing a rigorous analysis of growth rings. The range of 30 to 400 years is not out of line with the range of life spans in mammals, and one might expect to see similar biochemical reasons for differences in life span between bivalve species. In mammals, it appears to have a lot to do with mitochondria:

In animal cells, mitochondria are semiautonomous organelles [with] their own code and genome (mtDNA). The semiautonomy and restricted resources could result in occasional 'conflicts of interests' with other cellular components, in which mitochondria have greater chances to be 'the weakest link,' thus limiting longevity. ... (1) to what extent the mammalian maximum life span (MLS) is associated with mtDNA base composition? (2) Does mtDNA base composition correlate with another important mitochondria-associated variable - resting metabolic rate (RMR) - and whether they complement each other in determination of MLS? ... Analysis of 140 mammalian species revealed significant correlations ... To the authors' knowledge, it is the highest coefficient of MLS determination that has ever been reported for a comparable sample size. Taking into account substantial errors in estimation of MLS and RMR, it could mean that [this explains] most of the MLS biological variation. [This leads us to] mitochondria as a primary object for longevity-promoting interventions

Back to the bivalves: you can do more with growth rings than count them, as this research paper demonstrates. Growth rings contain a record of some aspects of the biochemistry of the clam over its life:

The ocean quahog Arctica islandica is the longest-lived of all bivalve and molluscan species on earth. Animals close to 400 years are common and reported maximum live span around Iceland is close to 400 years.

High and stable antioxidant capacities are a possible strategy to slow senescence and extend lifespan and this study has investigated several antioxidant parameters and a mitochondrial marker enzyme in a lifetime range spanning from 4-200 years in the Iceland quahog.

In gill and mantle tissues of 4-192 year old A. islandica, catalase, citrate synthase activity and glutathione concentration declined rapidly within the first 25 years, covering the transitional phase of rapid somatic growth and sexual maturation to the outgrown mature stages ( approximately 32 years). Thereafter all three parameters kept rather stable levels for > 150 years. In contrast, superoxide dismutase activities maintained high levels throughout life time.

These findings support the 'Free Radical-Rate of Living theory', antioxidant capacities of A.islandica are extraordinarily high and thus may explain the species long life span.

A little explanation here:

• Mitochondria churn out damaging free radicals as a side-effect of their job as the cell's power plants. The chain of biochemical events that follows on from this fact is a major component of age-related damage, disease and degeneration. You can look back into the Fight Aging! archives for an introduction to that topic.

• It has been demonstrated that soaking up the free radicals produced by mitochondria right at the source extends life span. This has been achieved by means of antioxidants like catalase, targeted to the mitochondria by gene therapy or other bioengineering means. This is quite different from taking antioxidants as a supplement, I should add; those don't go anywhere near your mitochondria, and thus don't do much good.

• So it's reasonable to theorize that if you happen to be a member of a species that naturally generates a lot of antioxidants around the mitochondria, you're going to live longer than members of another, similar species with worse luck in the antioxidant stakes.

It remains to be seen if this is enough to explain all of the disparity in bivalve life spans. Certainly, researchers are aiming in that direction to explain the ninefold difference in life span between naked mole-rats and other rodents of similar size, so it seems at plausible at this point in time. Personally, I hope that researchers demonstrate that mitochondrial biochemistry accounts for a very large chunk of aging and relative life span, given that the medical technology needed to repair and upgrade our own mitochondria is right around the corner.

Posted by Reason at 3:23 PM
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The goal of the more activist end of the healthy life extension community is nothing less than to engineer the defeat of degenerative aging: to develop medical technologies that make it possible to live in good health with no ticking clock driving you ever closer to suffering and death. This has been the case across decades of the modern community, from pre-internet years through to present day Methuselah Foundation initiatives, online collaborations and cryonics industry. Over at Depressed Metabolism, Aschwin de Wolf has republished a fine discovery from the late 1960s:

Aging is a biologic phenomenon. It involves basic changes that occur within living cells. The key to halting or reversing the aging process is our understanding of the life processes. It is most encouraging, therefore, to discover that we are beginning to understand the precise manner in which our bodies function.

The most spectacular advances in the past decade [the 1960s] have been in biology. With the use of equipment like the electron microscope and techniques such as X-ray crystallography, scientists have been able to examine the structure and workings of living cells on a molecular level. Light has been shed upon the mechanism by which genetic information is transferred from cell to cell, and simple types of DNA & RNA, the master chemicals involved in the process, have been duplicated in the laboratory.

As our understanding of the life processes increases, it is reasonable to assume that it will become possible to devise bio-engineering techniques to modify the aging process.

But this is all in the future. How far in the future depends upon us. It is common to hear people say that they believe that someday it will become possible to extend the human life span. This kind of prediction is misleading.

The problems involved in conquering aging have not been solved. They will never be solved unless people decide that they want to conquer aging - that they want to extend their lives. History has shown that man is capable of solving monumental problems once he sets his mind to it. At the turn of the century heavier-than-air flight was believed to be impossible, but the Wright brothers wanted to fly; just a few years ago rocket travel to the moon was looked upon as a fantasy, but scientists such as Werner Von Braun wanted to go to the moon. If we truly want to extend our lives - to maintain youth, vigor, and vitality indefinitely, we must become emotionally involved in the project.

This is just as true today, and it will continue to be true in the years ahead, right up until ongoing Strategies for Engineered Negligible Senescence (SENS) and related research mature into a grand scientific community and the first working technologies of rejuvenation. That will happen when enough people want it to happen, and are willing to devote their time and resources to the quest. The gathering of those people is going very well today, but many more are needed, and a road of decades lies ahead.

We know far, far more today about the aging process than the biologists of the 60s; specifically we have a good idea as to what aging is at the cellular and molecular level, and how we can repair it. The tools of biotechnology are many magnitudes more effective; a single laboratory can accomplish far more than the entire research community of four decades past. The initial era of basic discovery in aging biochemistry is done: now is the time to work hard to produce the first rejuvenation therapies and round out the gaps in knowledge.

Posted by Reason at 6:51 PM
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Publicity and volunteer work is gearing up for Aging 2008 at UCLA in late June. The event is a combination of free public symposium and scientific conference on developing the means to repair the cellular and molecular damage of aging. The symposium is one in a series of planned events to raise awareness and educate the public as to the real potential of longevity science:

On Friday June 27th, leading scientists and thinkers in stem cell research and regenerative medicine will gather in Los Angeles at UCLA for Aging 2008 to explain how their work can combat human aging, and the sociological implications of developing rejuvenation therapies.

...

• Dr. Bruce Ames, Professor of Biochemistry and Molecular Biology at UC Berkeley
• G. Steven Burrill, Chairman of Pharmasset and Chairman of Campaign for Medical Research
• Dr. Aubrey de Grey, Chairman and CSO of Methuselah Foundation and author of Ending Aging
• Dr. William Haseltine, Chairman of Haseltine Global Health
• Daniel Perry, Executive Director of Alliance for Aging Research
• Bernard Siegel, Executive Director of Genetics Policy Institute
• Dr. Gregory Stock, Director of Program on Medicine, Technology & Society at UCLA School of Medicine
• Dr. Michael West, CEO of BioTime and Adjunct Professor of Bioengineering at UC Berkeley

...

The speakers at Aging 2008 will argue that the near-term consequences of intense research into regenerative medicine could be the development of therapies that extend healthy human life by decades, even if the therapies are applied in middle age. Peter Thiel, president of Clarium Capital, initial investor in Facebook, and lead sponsor of Aging 2008, said, "The time has come to challenge the inevitability of aging. This forum will provide an excellent opportunity to look at the scientific barriers that must be overcome to substantially extend healthy human life, as well as the ethical implications of doing so."

We're all invited, so make your plans accordingly:

The Methuselah Foundation invites you to attend the FREE symposium:     Regenerative medicine may eventually deliver the genuine defeat of aging. How do you and your loved ones stand to benefit from the coming biomedical revolution? Are you prepared? Is society prepared? At Aging 2008 you will engage with top scientists and advocates as they present their findings and advice, and learn what you can do to help accelerate progress toward a cure for the disease and suffering of aging. To learn more, see our press release. Aging 2008 also serves as the opening session for the technically focused Understanding Aging Conference (learn more), running June 28th-29th at UCLA.

The Methuselah Foundation is looking for additional volunteers to help make this event a resounding success:

We need your help to prepare for and publicize these events - especially the June 27th symposium, when we have to fill Royce Hall with 1,800 people. Here's how you can immediately help to publicize this event:

1) Blog about Aging 2008; if you do, let us know and we'll add you to the Aging 2008 Blogroll

2) Put up a banner or button, and send banners/buttons to others:

http://mfoundation.org/aging2008/promote/

3) Send the May 18th press release to your network and media contacts:

http://mfoundation.org/aging2008/promote/Aging2008PressRelease.pdf

4) Promote through social networks, Twitter, and mailing lists

5) Put up/hand out flyers and postcards at colleges, bookstores, etc. in L.A. and surrounding regions:

http://mfoundation.org/aging2008/promote/#flyers

6) Help us get pre-event coverage: online, print, radio, and TV

7) Share Aubrey's videos (TEDTalk, Colbert Report, etc.) by putting them on your blog or sending them to friends:

http://mfoundation.org/aging2008/promote/#video

There's something for everyone - invite any friends that can help volunteer too! We need to tell the world that the aging process is an approachable challenge with the technologies we have at hand. Regenerative medicine is still in its infancy, and we can work to make the defeat of aging a key goal for this emerging field.