Scientists are making real inroads into replicating and controlling the cells and mechanisms of our immune system. Producing immune cells, directing their actions, deciphering the biochemistry of pathogens - all these pieces are waiting to be put together as a bioartificial immune system, many times more selective, efficient and resistant to damage than the basic version we're all equipped with. For added effect, it will also slay cancer cells and degrade the buildup of dangerous compounds, such as the amyloid beta associated with Alzheimer's disease.

A large component of age-related frailty stems from decline and malfunction in the immune system - chronic inflammation and loss of function due to overpopulation of memory cells are at the top of the list. But what if your immune system were augmented, pruned, and more controlled? Recurring viruses like CMV dealt with without the resulting bloat of useless memory cells; artificial antigens released as need to vastly improve defenses against invaders; a library of antigens kept in waiting, as large as you need, so that no new invader catches you unaware; hyperefficient destruction of known cancer cell types long before they can become a threat. The list goes on. The present problems of immune system aging could be eliminated, and the immune system made vastly more powerful, by the technologies just one or two steps down the road from what is taking place in laboratories and clinical trials today.

Here's one example of present groundwork:

researchers describe a method that can identify and clone human antibodies specifically tailored to fight infections. The new technology holds the potential to quickly and effectively create new treatments for influenza and a variety of other communicable diseases.

When an infection invades, the immune system goes to work manufacturing antibodies to fight it. Most of the antibodies created will have no effect, but a very few will bond to the invader and replicate to neutralize the enemy.

The new process develops a "smart bomb" for the immune system, using fully human monoclonal antibodies specifically designed to fight the infection without doing any harm to the body.

...

"We can recognize which cells are made and then make antibodies from them directly," Wilson said. "It's a rapid and efficient way to make fully human antibodies."

The key to a superhumanly quick response to pathogens is access to an evolving library of ready-made antibodies. One might imagine the future providers of immune system technology looking a lot like today's providers of anti-virus software for your computers, harvesting information on potential infections and streaming update information to bioartificial antibody manufactories in your bloodstream.

All of this isn't so far away. With the underlying technology in hand, it only takes a decade to build an information and delivery infrastructure like the one I've described above, and I can't imagine it taking more than two decades to complete and commercialize the presently nascent science. The only thing really holding us back is the ball and chain of oppressive regulation in the medical development field.

Posted by Reason at 7:06 PM
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Reason Magazine is running an interview with VC, trader and philanthropic investor Peter Thiel. It's of interest to those who would like more insight into the thinking that leads Thiel to support the activist outgrowth of the transhumanist community - specifically the Singularity Institute (hundred of thousands of dollars focused on development of general artificial intelligence) and the Methuselah Foundation (millions of dollars focused on radical life extension). The interview focuses far more on the former than the latter, but the reasoning is applicable across the board. On the one hand information technology, on the other hand biotechnology, both accelerating hard towards the promise of amazing future technologies:

I think [the Singularity Institute is] a group of really smart people working on an important problem. I think that the basic rule on philanthropy that I have is that I want to donate money to causes that are worthwhile but where there are no market-based mechanisms for them. There is a category of things that would benefit all of humanity but where the benefits are very diffuse and the costs are concentrated. Maybe it’s very long-term. So I focused my philanthropy on things with a 20-, 30-, 40-year horizon. The horizons are too long for a for-profit company to take advantage of, and the government and universities are not pushing things because maybe it’s too unconventional or it doesn’t easily fit into a particular political agenda or vision of the future. Those areas are probably systematically underfunded. It may be the only area of philanthropy that’s underfunded. ... I also have been doing some work on radical life extension, which I think is similarly underfunded.

...

I certainly think living longer is not a generally bad thing. I think that making sure the technology arc is positive rather than negative is not generally a bad thing. I think it probably would be somewhat mistaken to frame it in too narrowly selfish a way. It may be the case that the work being done on life extension is going to benefit people 100 or 200 years from now, but I think it still is a good thing to do it. My own guess is that I will live to age 100 to 120, so I'm frustrated that the technologies aren't going as quickly as they should because of government interference.

...

The question's not an abstract question about “Is it desirable for people to live X years?" It's "Is it good to have a cure for this form of cancer? Is it good to do something where your bodies and minds stay younger and healthier for longer than they otherwise would?" The [Leon] Kass approach encourages the rest of the society not to reflect about this. In the United States life is getting longer and longer, but we’re not thinking about it. If we’re actually going to live to age 100, the effect of Kass will be to encourage people to have a very unhealthy last 30 years because they will not have thought about and will not have prepared for it.

The future is what we make of it: either a golden era, realized through foresight and planning, or a wasted opportunity. The more people of influence to realize just how great the potential, the better.

Posted by Reason at 6:38 PM
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The latest issue of Rejuvenation Research is available online, with a strong focus on the mechanisms of Alzheimer's and other neurodegenerative processes. One of the more interesting papers describes the use of DNA vaccines in place of viral vectors in Alzheimer's immunotherapy. From Wikipedia:

DNA vaccines are third generation vaccines, and are made up of a small, circular piece of bacterial DNA (called a plasmid) that has been genetically engineered to produce one or two specific proteins (antigens) from a micro-organism. The vaccine DNA is injected into the cells of the body, where the "inner machinery" of the host cells "reads" the DNA and converts it into pathogenic proteins. Because these proteins are recognised as foreign, they are processed by the host cells and displayed on their surface, to alert the immune system, which then triggers a range of immune responses.

The early days of reprogramming our cells to do our bidding are starting to look quite sophisticated. Most immunotherapies for Alzheimer's disease (AD) seek to draft the immune system into destroying the accumulation of amyloid plaques thought to cause neurodegeneration. From the paper itself:

Although the clinical trials of active vaccination for AD patients were halted due to the development of meningoencephalitis in some patients, from the analysis of the clinical and pathological findings of treated patients, the vaccine therapy is thought to be effective. Based on such information, the vaccines for clinical application of human AD have been improved to control excessive immune reaction. Recently, we have developed non-viral DNA vaccines and obtained substantial [amlyoid beta] reduction in transgenic mice without side effects.

This issue of Rejuvenation Research is a weighty one, a little under twice as big as February's issue, and there's far too much of interest to list it all here. Head on over and take a look.

Posted by Reason at 5:46 PM
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Sirtris Pharmaceuticals is something of a figurehead for the resources flowing into calorie restriction research at all levels over the past few years. As I'm sure you saw in the media, Sitris was recently acquired by GlaxoSmithKline for a fair chunk of change; in an age of oppressive regulation and the enormous investment in time and money required to satisfy that regulation, this is the preferred exit strategy for investors, as it's the only one likely to happen rapidly. Some thoughts from those who watch the industry below:

Sirtris to be acquired by GlaxoSmithKline:

Sirtris has focused on the commercial development of clinically useful sirtuin activators, which are predicted to be useful as anti-diabetic drugs. Data from academic labs have suggested they could be of even wider use, e.g., in increasing exercise tolerance or treating inflammatory disease. Underneath it all, of course, is the knowledge that the the sirtuins were initially identified as longevity assurance genes; the subtext of all discussions of sirtuin activators is that they may mediate their beneficial effects by slowing aspects of the aging process itself.

The acquisition of an small company at a large premium (the offer was more than 80% higher than Sirtris' market cap) by a pharmaceutical giant is one of the first demonstrations that the drug industry is taking seriously the idea that there's money to be made in treating aging per se rather than all of the associated conditions separately

Sirtris, as you'll recall, is centered on the exploration and manipulation of sirtuins such as SIRT1. Ouroboros also provides an overview of what is presently known about the role of SIRT1.

$720 Million Worth of Sirtuin Research:

Of course, Sirtris hasn’t officially been targeting life extension drugs, at least not in the near term. A number of these potential life-extending biochemical pathways are tied up with insulin signaling, which makes sirtuin-targeted drugs a natural for diabetic therapy as well. Sirtris has reported encouraging data for just that indication. If a sirtuin-based drug is going to make it to market, that’s a good bet for how it’ll do it. ... Once one of these drugs is approved, it’ll have the biggest, strangest potential for off-label use that anyone has ever seen. Oh, that’s going to be something to watch. GSK is well aware of this - I’m not saying that it’s part of their business plan, but when you see their head of drug discovery talking to Forbes and tossing the word "transformational" around, you know that they’ve thought beyond a replacement for Avandia.

...

That’s the truth, all right, and it’s going to be fascinating to watch things develop. As I was saying here the other day, a drug for aging is a perfect example of something the FDA has absolutely no idea of how to approach. Well, it’s not just the FDA, come to think of it: how on earth would you design a Phase II trial for life extension? How long would it take? What’s your clinical endpoint? And further on, how long will you want to monitor your Phase III patients (recall Pfizer’s recent follow-up of Exubera trial participants? How long will it take before you could be sure that some horrible bargain wasn’t struck along the way?

Notice that the largest problem for the future of longevity medicine in the established research and development community is the FDA and its heavy-duty, risk averse structure of trials after trials after trials. The cost is immense, and in most cases utterly out of proportion to any rational cost-benefit analysis of a new medical technology. So those technologies simply aren't commercialized, joining the vast sea of wasted potential that attends all imposition of regulatory cost.

The simple answer to the questions in the quote above is that you don't run a Phase II trial for life extension strategies. It doesn't make sense to talk about these structures and strategies rigidly applied to this case, but the present weight of regulation doesn't allow for the sort of free competition and innovation under pressure that always produces working, practical answers.

Since the FDA will never approve an intervention into the aging process - as aging is not recognized as a disease, and the FDA only approves treatments for disease - the underlying technologies are not applied to that end. No-one invests in medicine that cannot be sold due to government prohibition. Instead, the promising science is diverted into the same old process of patching up the very end results of age-related damage. It's that simple and that wasteful.

Absent a very overdue revolution, change to this sorry state of affairs will be slow and expensive, a matter of lining the pockets of politicians to re-order some of the destruction they've caused. A part of that long change process is the assimilation of potential new longevity science into organizations large enough to influence the FDA's mandate. Here, we see one of the first acts in that play.

Posted by Reason at 6:27 PM
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A review paper I noticed today reminded me of the relationship between body temperature and longevity. Calorie restriction leads to lowered body temperature - as well as extended healthy life - in mice, but unrelated methods of lowering body temperature over the long run also seem to extend longevity to some degree. For example, see this research from a couple of years ago:

Was calorie restriction itself responsible for longer lifespan, with reduced body temperature simply a consequence? Or was the reduction of core body temperature a key contributor to the beneficial effects of calorie restriction? Conti and colleagues wanted to find out. To tackle the problem, the scientists decided to try to lower core body temperature directly, without restricting food intake.

...

Conti and colleagues decided to focus their efforts on the preoptic area of the hypothalamus, a structure in the brain that acts as the body’s thermostat and is crucial to temperature regulation. Just as holding something warm near the thermostat in a room can fool it into thinking that the entire room is hotter so that the air conditioning turns on, the Scripps Research team reasoned that they could reset the brain’s thermostat by producing heat nearby.

To do so, they created a mouse model that produced large quantities of uncoupling protein 2 in hypocretin neurons in the lateral hypothalamus, which is near the preoptic area. The action of uncoupling protein 2 produced heat, which diffused to other brain structures, including the preoptic area. And, indeed, the extra heat worked to induce a continuous reduction of the core body temperature of the mice, lowering it from 0.3 to 0.5 degrees Celsius.

The scientists were then able to measure the effect of lowered core body temperature on lifespan, finding that the mice with lowered core body temperature had significantly longer median lifespan than those that didn’t. While this effect was observed in both males and females, in this study the change was more pronounced in females - median lifespan was extended about 20 percent in females and about 12 percent in males.

Some researchers would like to pin temperature-dependent longevity on the rate of chemical reactions in the body (reaction speeds generally being proportional to temperature), but I suspect that's too simplistic. An alteration in the rate at which mitochondrial processes generate damaging free radicals sounds more plausible, driven by some temperature-sensitive signaling and control process.

The interesting question with regard to this is what proportion of calorie restriction benefits stem from this mechanism - as opposed to, say, the loss of visceral fat, changes in metabolic control pathways, increased autophagy, other regulatory changes in cells, and so forth. None? A tenth? A third? What? As we look at ongoing work to produce calorie restriction mimetic drugs, based on manipulating the biochemical pathways researchers discovered through research into calorie restriction, how much benefit will these mimetics provide for people who still have visceral fat and a high body temperature?

Posted by Reason at 6:21 PM
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As I mentioned over at the Longevity Meme, SAGE Crossroads seems to be putting forth new material on policy and longevity science once more. Looking at some of the podcasts uploaded this year, I notice one on the Longevity Dividend initiative with Daniel Perry of political advocacy groups Alliance for Aging Research and CAMR, amongst others.

#35-Longevity Science-Setting the stage, the longevity dividend:

All you have to do is go into any bookstore in this country and go to the health section and you’ll see lots of titles about ending aging or immortality or stopping aging in its tracks. I think there is a lot of debate over whether that’s conceivable, but I think there is an emerging belief that we can slow down the processes of aging and make real achievements within a reasonable period of time, the next 10-15 years, that could buy back for people now living 5-7 years of healthy, productive life. As one gerontologist said, it ought to take 80 years to get to 60. Now that may be a bit more ambitious that what I’m talking about. I’m talking about seven years not 20 years, but there is a growing feeling among leading scientific authorities that based upon what we know works in laboratory animals, including apparently based on recent data, rhesus monkeys, a very close cousin to human beings. It could be possible that we could engineer healthier, more vital, more satisfying life for people in their 70s, 80s, and 90s in our lifetime.

Institutional outlooks are usually incrementalist, aiming for the smallest set of changes possible under present circumstances, as the incentives within institutions discourage any other course. In that respect, the Longevity Dividend is the output of institutional thinkers. What you see above this is more or less the view from inside the government funding monolith, where suggesting even a modest target for increasing healthy life span is a major advance, hurdle and negotiation.

Meanwhile, outside the institutional gates is where you'll find the serious attempts to create revolutionary change in the aging research community and develop disruptive technologies from the latest longevity science. As I said at the time the Longevity Dividend was first put forward:

this proposal is late to the party, fails to acknowledge those who have been advocating similar approaches for some years, and touts a target for gains in healthy life span that is somewhat less than the actuaries and system biologists think will be attained in the next 10 to 20 years by present trends and research directions.

...

The Longevity Dividend proposal is primarily a political position - which should instantly explain most of its deficiencies to those who follow the way in which funding politics works. It's the first step in a long engagement with large-scale government funding sources (such as the National Institute on Aging) in an attempt to steer future funds into the sorts of moderate programs supported by its authors. That Miller, et al, are doing this at all illustrates, amongst many other things, a concern that future funding will dry up in favor of groups presently moving to advocate healthy life extension - such as those system biologists, or supporters of the Strategies for Engineered Negligible Senescence.

My prediction for the next decade: the trail to radical life extension, and to increasing public understanding and support for medicines to repair aging, will be blazed by philanthropic and private venture funding.

Posted by Reason at 7:35 PM
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I've been meaning to mention that molecular biologist and healthy life extension advocate Attila Chordash is in the midst of blogging the construction of his PhD thesis. His long term interest is in what he calls partial immortalization (or, alternately, systemic regenerative medicine) - as much healthy life extension as possible attained through period replacement of organs and vital cell populations, as well as via manipulation of stem cells in situ. I have been varyingly skeptical of the degree to which this alone is sufficient for radical life extension:

• Regeneration Is Not Rejuvenation
• Inserting Repair of Aging Into Tissue Engineering

But it is still an interesting concept, and will clealry be explored in the years ahead, given the massive levels of funding and research interest justifiably directed towards stem cell science.

But back to the thesis, which is a good insight for those interested in what is presently going on down in the trenches of the research community:

During my PhD work I’ve done various stem cell transplantations (local and systemic) into brain, heart, muscle tissues using different stem cell sources, just like freshly isolated bone marrow derived cells (hematopoietic, mesenchymal stem cells), murine embryonic stem cells, cultured hematopoietic stem cells. And I was heavily involved in the mechanisms by which exogenous stem cells can contribute to host tissues and the way these exogenous cells and lesion models can motilize the built in endogenuous stem and progenitor cell populations.

So for me the unifying concept behind is a kind of systemic approach, that is to collect many stem cell data from various tissues, organs, compare them to each other and derive some unifying principles from them that could be adapted to other tissue environments too.

Chordash is not the only person engaged in online thesis building in the regenerative medicine space. I view this as a facet of the overall trend in scientific work towards more open access, meritocratic open review, a gift economy of information, and incremental publication by release. The present information infrastructure in the scientific community - much of it still geared to and informed by an era of paper libraries and hand-delivered mail - isn't up to the task of enabling efficient management and utilization of data at scale. Change is underway, and must go a lot further if the pace of research is to keep up with the pace of data generation. As Chordash puts it:

after all, scientists should conduct nice experiments and publish their results in short, inforich and accessible research papers in order to share it ASAP with the research community, not in book-length, otherwise unaccessible PDFs

The ideal infrastructure would look - from above the API layer - something like a vast distributed and cross-referenced database, constantly updated and constantly accessible to automated discovery and correlation agents, raw data neatly split out from conclusions and theories about that data. As even small fields grow far beyond the ability of one researcher - or one small team - to encompass and understand, automation of the time-consuming parts of academic research will become increasingly necessary.

Posted by Reason at 5:26 PM
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Every once in a blue moon, I'll participate in a blogmeme. Blink and you'll miss it, right back to longevity science and advocacy the next day. This is a small one put forward by Michael Graham Richard:

Here are 7 questions that I would like to ask to the following people: Michael Anissimov, Jamais Cascio, Tom McCabe, George Dvorsky, Steven Smithee, Randall Parker, and Reason of Fight Aging.

1. What would you nominate as the best idea that anybody has ever had? Why?

From a utilitarian point of view, the formalization of the scientific method that produced the present long-surviving community able to sift and preserve truth from the great foaming sea of lies and mere belief. This is more than a matter of the method, but also the way in which the method is presented, and the way in which scientific communities govern and propagate themselves. We'll put Francis Bacon forward as the figurehead originator for the modern world, though it was an idea whose time had come (once again) in his lifetime.

Men have sought to make a world from their own conception and to draw from their own minds all the material which they employed, but if, instead of doing so, they had consulted experience and observation, they would have the facts and not opinions to reason about, and might have ultimately arrived at the knowledge of the laws which govern the material world.

Imagine a world in which a community as devoted to the practice and protection of the scientific method had emerged and sustained itself as early as seems possible, say perhaps 2,000 to 3,000 years ago in China. How much further could we have advanced by now?

2. What non-fiction book do you think everybody should read? Why?

Anything that provides a solid, readable overview of the Austrian school of economics as it applies to everyday life, modern democracies and the choices we make. Widespread and profound economic ignorance - meaning ignorance of the way in which our world really works, leading to an inability to identify and address the many problems and evils that exist - is at the root of the yawning chasm between what is and what might be.

The very advanced class should go straight to the online edition of Mises' Human Action, while everyone else might consider starting with the very readable and recently released "The Revolution: a Manifesto" by Ron Paul, or perhaps Economics for Real People.

3. What fiction book do you think everybody should read? Why?

Atlas Shrugged - though I imagine that if you're were ever going to read it, you probably have already. Still, put aside anything you know about the author and read it as a work in isolation. The most important lessons in life revolve around the following triad: that choices matter deeply, self-knowledge is power, and hard, honest work is required to attain any goal worth having. Rand's writing will make you think about these things, and you will be the better for it.

4. What technology has most changed your life in the past 10 years and why? What technology do you think will have the biggest impact on your life in the next 10 years and why?

In both cases, the communication and computation infrastructure that sustains the internet; it opens up myriad opportunities and economic niches that were impractical in earlier ages. Bandwidth and information density in component peripherals matters, which is why, I imagine, that the mobile communication revolution hasn't really changed matters for me all that much. The next interesting phase transition, for people like me at least, will occur when you can carry the all the function and utility of a home office and high bandwidth connection in your pocket for a reasonable amount of money. This is more a matter of sorting out the peripherals than the bandwidth, or at least it looks like the peripherals have further to go, but at that point a truly nomadic lifestyle is quite plausible once again for a significant section of the populace.

5. What piece of music would you want with you on a desert island (that has a functioning stereo, of course)?

A spoken word piece on how to build a decent transmitter from the components of a stereo. For the rescue request. It can be set to sparse drum and flute accompanyment if you like.

6. What is the most interesting thing you are working on/reading about/writing about these days?

In terms of what I am watching from the sidelines, even more than the advancing science of longevity, I think it is the ongoing cultural upheaval in the gerontology community that is most engaging. We are witnessing a sea change of paradigm and transfer of influence, from a community that dared not even talk about extending healthy life span, to a vocal and engaged community that now spars in public over how best to do it, and how long it will take.

This is of great importance. The science is just work and money - large amounts of both, of course, but that can always be found if the will to progress exists. The real battle is over whether the science will be turned to the purpose of longevity in any significant way at all.

7. Looking ahead, are you an optimist or a pessimist? Why?

One has to be an optimist about the progress of science and technological capabilities. It's a fast uphill ride, and the next three decades will see the advent of powerful technologies like molecular manufacturing, affordable orbital lift capacity, enormously powerful computers for the cost of sand, organ regrowth and the absolute control of human cells.

I am very pessimistic about the influence of dominant forms of political organization in the developed world and the corrosive influence upon culture that follows - the vanishment of ambition, education, self-sufficiency, responsibility and accountability. Progress will be hindered and shackled, especially in the world of medicine. All the incentives are horribly misaligned, towards stagnation and poverty of service, and - short a long overdue revolution - will only get worse.

Posted by Reason at 2:59 PM
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You can compare and contrast the views of biomedical gerontologist Aubrey de Grey (chair of the Methuselah Foundation, originator of the Strategies for Engineered Negligible Senescence) and gerontologist Robert Butler (president of the International Longevity Center and one of the folk behind the Longevity Dividend initiative) in a series of short videos available at Big Think. A small sampler can be found at the Big Think blog:

What is the point of knowing your own genetic code? For many scientists, the genomic era promises to entail the ultimate type of "preventive medicine," preventing not only biological disease, but aging itself. [Biomedical gerontologist] Aubrey de Grey suggests that an ending to aging would limit suffering since "aging just doesn’t kill people. It kills them horribly." It’s something we may not quite be prepared to deal with "because aging has been considered inevitable for so many millennia."

Dr. Robert Butler too believes that in a hundred years, we’ll be living much longer, better.

The rest of their video segments can be found elsewhere in the site:

• Aubrey de Grey's videos
• Robert Butler's videos

Aging to death is a terrible fate, but human ingenuity and application of the scientific method have banished many other horrible fates from most lives in past decades. We live in an age of revolution and accelerating prowess in computation, biotechnology and medicine. So much is possible today that could not even have been planned two decades ago. Scientists know more than enough now to work to prevent and repair the root causes of age-related suffering, degeneration and frailty - all that's needed is the public support and will to move forward, to seek a cure for degenerative aging.

Posted by Reason at 7:50 PM
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You might recall that mice engineered not to express the protein p66Shc live 30% longer, but it's not entirely settled as to why this is the case. The protein p66Shc is required for some methods of programmed cell death in response to damage and failing function, so removing it lowers the rate at which cells destroy themselves in response to stresses:

Free radicals (a category that includes reactive oxygen species) lead to oxidative stress, a term for damage caused to cellular mechanisms by these chemicals. Cells destroy themselves via apoptosis in response to excess oxidative stress, a process initiated in the mitochondria, so as to prevent their own failing mechanisms causing further damage to the body - but the processes of identifying just when is most advantageous to do so are quite varied and complex. The protein p66Shc [is] an important part of one scheme by which a cell starts in on destroying itself.

...

p66Shc knockout mice exhibit higher catalase activity [and] removing p66Shc extends life - but is this because of a lowered rate of apoptosis with oxidative stress, or is it in fact the higher levels of catalase, an antioxidant that helps soak up the free radicals before they break things? As I'm sure regular readers recall, engineering mice to have more catalase in their mitochondria is good for a 20-30% boost in life span.

There's more on the mechanisms of p66Shc over at ScienceDaily today:

Activated by cellular stress, four p66Shc molecules form a stabile complex via Cystein-Cystein interactions. Only this complex can introduce the controlled cell death by causing the mitochondria to burst. The p66Shc activity can be arrested by the Glutathione and Thioredoxin cellular protective systems, which are capable of breaking down stress damages, substances that cause stress and the activated p66Shc complex. "p66Shc acts in this capacity as a stress sensor", explains Dr. Steegborn.

"The cell's suicide program is apparently only started when these protective systems can no longer handle the cellular stress, and are subsequently also no long capable of deactivating p66Shc that has already been activated."

...

Mice in which the gene for p66Shc, which is closely related to the human equivalent, has been removed do in fact live some 30% longer than normal mice, but the suspicion is that this gain in lifespan is achieved at the expense of correct function; i.e., that the organism is more susceptible to malfunctions due to cell damage.

Which is interesting, but my money is still on the catalase theory.

Posted by Reason at 6:47 PM
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It's a matter of common sense that putting your skin out in the sun is not good for its longevity. As it turns out, the way in which the sun damages your skin is more subtle than a blunt effect of direct radiation. Here's a look at one part of the way in which that happens:

Cutaneous aging occurs through 2 biologically distinct processes: intrinsic and extrinsic aging. The first is a naturally occurring process that results from slow tissue degeneration. In human dermis, intrinsic aging is characterized by 3 features: atrophy of the dermis due to loss of collagen, degeneration in the elastic fiber network, and loss of hydration.

In contrast to intrinsic aging, extrinsic aging is due to environmental factors. Since ultraviolet (UV) exposure is the principal cause of extrinsic aging, it is often referred to as photoaging. At the microscopic level, the distinguishing feature of photoaging is a massive accumulation of elastotic material in the upper and middle dermis, a process termed solar elastosis. Using recombinant DNA technology, it has become possible to demonstrate that UV radiation can activate the human elastin promoter. This provides a mechanism for enhanced elastin biosynthesis, which contributes to the clinical and morphologic changes observed in photoaged skin.

In other words, solar radiation changes the way skin is programmed to form and repair itself - for the worse. So much of aging is caused by malfunctions in the signal and control mechanisms of the body, processes necessary to the normal function of tissue run awry or amok, causing damage or - as in this case - changes in the structure of tissue that reduce its ability to function. Inflammation in the skin brought on by solar radiation is another example that contributes to aging of the dermis; necessary mechanisms subverted to set damaging processes in motion.

Posted by Reason at 5:53 PM
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Longevity science advocate Barbara Logan has organized an evening with biomedical gerontologist Aubrey de Grey at the Orlando Science Center in Florida this May 12th, sponsored by the Millard Foundation, and boasting a slick mini-website. Good work - I'm always pleased to see hardworking members of the healthy life extension community doing more to move matters forward:

Engineering an End to Aging, an evening with Dr. Aubrey de Grey

Find out why MIT's Technology Review, the New York Times, the Economist, Fortune Magazine, Popular Science, Barbara Walters, 60 Minutes, even Stephen Colbert think Dr. Aubrey de Grey may have found the way to end aging.

If you're in Florida this May, this is an excellent chance to hear de Grey speak and ask your questions about his Strategies for Engineered Negligible Senescence, the longevity science book Ending Aging and the ongoing research funded by the Methuselah Foundation.

Enjoy Dr. de Grey's engaging and entertaining speaking style. Get a chance to talk to this pioneer in the world of longevity research. Learn about the latest breakthroughs in life extension. Network with influential individuals interested in the future of bio-tech here in central Florida.

You'll find PDF fliers and a press release at the website for the Orlando event. If you live in that part of the world, do your part and pass the promotional material along to those who would be interested.