A cluster of posts over at FuturePundit show how advances in computing technology are driving the biotechnology revolution. The call for information is strong, and the computing industry is answering it - and then some. This time next decade, we're going to be swimming in so much information about human biochemistry - and so many more people are going to be producing it on demand - that the limit to progress will be our ability to manage all this data. The answers and paths to cures will all be there, waiting to be found by data miners.

New Technology To Lower DNA Synthesis Costs:

Using current methods, programmed synthesis of a typical gene cluster costs thousands of dollars. The system developed by Gao and her partners employs digital chemistry technology similar to that used in making computer chips and thereby reduces cost and time factors drastically. Her group estimates that the new technology will be about one hundred times more cost- and time-efficient than current technologies.

The harnessing of electronic technologies to solve problems in biological science and biotechnology will lower costs and accelerate the rate of advance by orders of magnitude. Both the reading of DNA (sequencing) and the writing (synthesis) will become extremely cheap.

TJ Rodgers Sees Demand For Nanopore DNA Sequencers:

The technology needed] to understand the gene sequence - that's going to go to silicon. There are startups in Silicon Valley coming into our company saying they want us to build holes so small that one DNA molecule will fit in them. They want to watch it fluoresce and find out what it is. And they want millions of chips.

Founder Population Genetic Scans Accelerate:

the most interesting part of the article mentions that Genizon has used improvements gene chip technology to speed up their genetic studies by more than an order of magnitude.

The initial Genizon map, completed in 2004, was created from 1,500 members of the Quebec founder population and had about 81,000 markers. Genizon has now improved its gene hunting capabilities even further, by using a gene chip produced by Illumina, a genetic toolkit company in California, which incorporates markers from both the HapMap and original Quebec map, for a total of more than 350,000 markers per individual. Studies that initially took scientists three months now take just a week

Financial Experts Debate Implications Of Aging Population:

In 1974, it cost $100 million to sequence a gene. Today, it cost $3, and by 2013, it will be 3 cents.

...

I think all the conventional ways to project future increases in life expectancy are greatly underestimating the effects of coming advances in biotechnology. Our knowledge is not simply increasing with the same fixed amount of knowledge added to the sum total of our knowledge every year. Rather, the rate at which we can collect knowledge is increasing. That trend looks set to continue for decades to come.

...

People who do not see this biotechnological revolution in rejuvenation on the horizon are akin to someone in 1965 saying that of course computers must take up whole rooms and that we'll never have desktop computers which are many orders of magnitude faster than 1965 mainframes. We are going to gain the ability to manipulate cells and genes on a level that will allow us to repair our aged bodies. There's nothing about the nature of physical reality that precludes our developing the ability to do this.

These last points should be common wisdom, and we should all do our part to try and make them so. That biotechnology will reach these heights in the next 20 years is something of a foregone conclusion at this point. The real issue is whether these enabling technologies will be used effectively and directly to extend the healthy human life span, rather than simply stumbling forward fixing each problem as it starts to kill large numbers of people, and slowly extending life spans as a side-effect.

We can do better than incidental healthy life extension, but it is not a given that this will happen, nor that it will happen in time to help those suffering age-related degeneration today, tomorrow, or decades from now. That is what we fight for - in the end, it becomes a matter of life and death for all of us.

Technorati tags: activism, biotechnology, life extension

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A conversation, in the wider modern context, is something that wends its way across months of time and hundreds of thousands of minds via blogs, emails, other websites, letters, the spoken word, radio, TV, magazines and newspapers, to name but a few of the possible paths. Branching and joining threads of thought and ideas hop and jump from media to media - but the most recent, internet-era additions to the possible paths of conversation are what really makes it all froth and bubble. Important activities and advocacy coalesce from this conversation as a matter of course; meritous and popular ideas are far more likely to gain the support they deserve when the cost of communication is so low. The MPrize for anti-aging research and the all-volunteer Methuselah Foundation are excellent examples of firm and directed organizations that came from the foam of the internet; spontaneous self-organization in action.

Unfortunately, some topics just can't be discussed well in email, blog and website; they are drowned out by the efforts of those trying to make money. So it is with scientific anti-aging research and the vast sea of static produced by the purveyors of useless, all brand and no cattle "anti-aging" products. Just take a look at what is seen when searching for any sane, non-monetary, responsible discussion of anti-aging science on Google, Google News, Google Blog Search and Technorati - a blizzard of junk and nonsense. It's the same everywhere you look, a storm of short-termist profit seeking that destroys the primary utility of the internet for these concepts, making it impossible for diverse groups to collaborate, exchange ideas and build new organizations as a part of a serious, ongoing cultural conversation on anti-aging science.

So we all lose out - including the short-termists. How's it feel to be contributing to your own demise, you out there with the HGH ads, cherry-picked studies and spam sites?

I briefly set down a few thoughts on the future of branding and discussion last month. Anti-aging is beyond salvage as a term for discussion; we should move on and use other language to describe the technologies of healthy life extension and advanced medicine to extend healthy life spans.

Technorati tags: activism, advocacy, anti-aging, life extension

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As an addendum to the interesting telomerase, mitochondria and oxidative stress research noted at the Longevity Meme, here's another related paper from those posted to sci.life-extension today. This one looks at oxidative stress, the resulting damage to mitochondrial DNA, and its relation to the general state of your tissues:

Mitochondrial DNA (mtDNA) mutations appear to be associated with a wide spectrum of human disorders and proposed to be a potential contributor of aging. However, in an age-dependent increase of the common 4977bp deletion of human mtDNA still many unanswered questions remain.

...

In vitro studies analyzing human normal cells transfected with telomerase (BJ-T) revealed that oxidative stress (OS) - a well accepted promoter of aging - induced 4977bp deletion and point mutations

...

In conclusion, in heart tissue, the amount of the 4977bp deletion increased in an age-dependent manner and it was more detectable after the 4th decade of life, although there was some scatter in the data. Since, apoptosis was induced by the mitochondria-mediated pathway only in transformed cells, the role for apoptosis in normal tissue of the aging heart remains unclear.

This is what exploratory science looks like in a complex field - lots of teams prodding at the knowns and unknowns, and way more loose ends than people to make connections. As shown here, using telomerase on in vitro cell cultures doesn't seem to be a good way to understand what is going on in the body if - as other researchers claim - telomerase greatly influences the workings of oxidative stress and rates of mitochondrial DNA damage.

Still, there's no such thing as useless knowledge; it's all an advance. Yet we already know that technologies to replace damaged mitochondria could plausibly be developed in the same timeframe as the task of understanding what exactly all this biochemistry means. This, in essence, is the difference between engineering approaches and scientific approaches; you don't need full and complete knowledge to achieve a good result. In this case the good result would be healthy, undamaged mitochondria in old age, removing whatever contribution that damage makes to the aging process. While it would be beneficial to completely understand all the biochemistry and processes involved, researchers can achieve important medical goals without that full understanding - and in advance of it.

Technorati tags: aging, science

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A (skeptical) discussion is underway over at the sci.life-extension group on a recent paper that suggests the constant fusion of mitochondria is a challenge to mitochondrial theories of aging. You might want to start with a primer on mitochondrial fusion before going too much further:

Fusion of mitochondria serves to mix and unify mitochondrial compartments. This is of particular importance for the inheritance and maintenance of the mitochondrial genome

...

Ono et al. (2001) established two respiration-deficient HeLa cell lines, each carrying a pathogenic mutation in a different mitochondrial tRNA gene. Hybrids obtained by fusion of these cells showed restoration of normal respiratory activity within a few days.

...

These findings suggest that mitochondrial fusion counteracts the manifestation of [mitochondrial DNA (mtDNA)]-linked diseases. Moreover, it has physiological significance in individuals born with intact mitochondrial genomes. The highly oxidative metabolism of mitochondria increases the risk for mtDNA damage. Thus, lesions and point mutations of mtDNA accumulate during aging and result in the loss of bioenergetic function (Wallace, 1992; Nagley and Wei, 1998; Raha and Robinson, 2000). Fusion of mitochondria might contribute to the maintenance of respiratory activity by allowing trans-complementation of somatic mutations that accumulate in mitochondrial chromosomes over time (Ono et al., 2001), and thus mitochondrial fusion may be a crucial defence mechanism against cellular aging.

But back to the discussion - I'd agree that it doesn't look like a very defensible assertion, but as noted, the theory would have to explain how it all fits together.

In mammalian cells, there is an extensive and continuous exchange of mitochondrial DNA (mtDNA) and its products between mitochondria. This mitochondrial complementation prevents individuals from expression of respiration deficiency caused by mutant mtDNAs. Thus, the presence of mitochondrial complementation does not support the generally accepted mitochondrial theory of aging, which proposes that accumulation of somatic mutations in mtDNA is responsible for age-associated mitochondrial dysfunction. Moreover, the presence of mitochondrial complementation enables gene therapy for mitochondrial diseases using nuclear transplantation of zygotes.

...

I don't agree with their proposition. However the [mitochondrial / free radical theory of aging] needs to account for this. The results they are reporting obviously don't seem to be happening in vivo. It does perhaps offer the hope that mitochondria may be reparable.

Mitochondrial fusion has the look of a process that slows the rate at which accumulating damage impares efficiency. Without it, you'd keel over much more rapidly (leaving aside all the other reasons as to why the process is or might be necessary for life), but that doesn't challenge the basic concept of mitochondrial DNA damage as a root cause of aging.

I think that groups have already demonstrated that mitochondria can in principle be repaired, at least by outright replacement of their DNA via protofection.

Technorati tags: aging, life extension, science

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Over at the Paul F. Glenn Laboratories for the Biological Mechanisms of Aging, you'll find details on the upcoming June 5th symposium on the biology of aging. The program is a short list of the present high-fliers in the more conservative mainstream of aging research.

The Glenn Laboratories website is worth a longer look while you are over there:

The Paul F. Glenn Laboratory is dedicated to understanding the mechanisms of normal aging and the development of interventions to delay its onset and progression, thereby extending the healthy years of human life.

...

Seeking to accelerate the pace of research into the molecular mechanisms that govern aging, Harvard Medical School and philanthropist Paul F. Glenn, an alumnus of Harvard Law School and founder of the Glenn Foundation for Medical Research have launched the Paul F. Glenn Laboratories for the Biological Mechanisms of Aging. The new resources will serve as a magnet to attract additional support for the potential creation of a larger Institute for Aging Research at Harvard Medical School.

Thanks to those pushing hard at the wheel of progress, this forward-looking viewpoint is slowly becoming the position of the scientific mainstream. Discussion and debate is gravitating towards fundraising, timescales and methodologies, moving past the hoary old stumbling block of whether or not to aim for healthy life extension through advanced medical technologies.

Technorati tags: aging, gerontology, life extension, science

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The 2006 Regenerate World Congress on Tissue Engineering and Regenerative Medicine is underway in Pittsburgh, with the McGowan Institute for Regenerative Medicine playing host.

The 2006 Regenerate World Congress focuses on tissue engineering/regenerative medicine approaches to restoring the function of damaged or diseased tissues and organs. The event will also concurrently explore the platform/enabling technologies and many of the broader cross-cutting challenges facing this emerging field of biomedicine. The event is designed for those engaged, or interested in, the fields of cellular therapies, medical devices and artificial organs, biomaterials, bioengineering and clinical translation.

Our goal: To advance tissue engineering/regenerative medicine science and foster interactions that may more rapidly result in new technologies that will benefit patients worldwide.

A very interesting, full agenda is online; you should spend some time browsing. So much more is going on than just the highlights that make the popular science pages, and this is a burgeoning, busy field. From the local Pittsburgh press:

"The public doesn't really understand just how far this science has come," said Alan Russell, conference chairman and director of the McGowan Institute for Regenerative Medicine in Hazelwood.

Regenerative medicine - the ability to replace failing and diseased organs - is a vital part of the path to far longer, healthier lives. It isn't the whole path, however: other aspects of degenerative aging must be conquered. It's going to be a big job, but it's possible and plausible; it can be done. Radical life extension through advanced medical technology will happen. The only question is whether we can help it to happen soon enough to benefit those reading this today.

Technorati tags: life extension, regenerative medicine

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Larger donations are starting to roll into the Methuselah Foundation on a semi-regular basis now, a result of the good work done by Foundation volunteers and the tireless efforts of biomedical gerontologist Aubrey de Grey - and of course, a result of the actions of the many people who have stepped up to donate in support of the MPrize for anti-aging research over the past three years. It is the breadth and variety of modest donations, helping hands and expressions of support that illustrates the worth of the Foundation's mission to wealthy philanthropists and funding organizations.

A check for $50,000 for LysoSENS research arrived last week from entrepreneur Jay Walker, and today I have this from Foundation cofounder Dave Gobel:

We are in receipt of a check for $25,000 from the Novogratz Family Foundation :-) The donor wishes the funds to be applied:

- $12,500 to the Rejuvenation Mprize
- $12,500 to SENS Research and administration

Well done all!

If you are new to the Methuselah Foundation and its mission, consider reinforcing this success by joining The Three Hundred. Show your support for the development of real, working methods to eliminate age-related frailty and extend the healthy human life span!

Technorati tags: activism, life extension, MPrize, SENS

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People are chatting more about longevity, aging and the scientific way forward to significant healthy life extension; this is a good thing. I'm of the opinion that living a longer, healthier life is such a compelling proposition - and the common objections so easily demolished - that more widespread conversation can't help but swell the ranks of those who support and act to build a future of working anti-aging medicine.

With that in mind, here are a couple of recent posts that I think are worth a few minutes of your time - starting with one that I think hits the utilitarian spot without even going past the title:

Longevity economically good, worth investing in making more longevity:

It is clear that living longer is good for people and for the economy. It is clear that there is lot more that can be done to raise human life expectancy and life span. We should spend a lot more on pushing technological horizons outward in an aggressive way.

Mark Walker's superlongevity talk for the TTA:

Last night at the University of Toronto's Bahen Centre for Information Technology, Dr. Mark Walker delivered a presentation about the ethics of radical life extension, or as Walker refers to it, 'superlongevity.' The talk was organized by the Toronto Transhumanist Association.

The talk was party adapted from his recent paper, "Universal Superlongevity: Is it Inevitable and is it Good?"

Perpetual Life:

Aubrey de Gray has brought it all front-and-center, suggesting that life extension is no longer out of reach. In our usual chronocentric arrogance, we believe this is all new territory. There are innumerable technical discussions and observations, but the philosophical discussions seem to be brief, and not very interesting.

A: I don't know as I'd want to live to be 150.
B: Yeah, but you might if you had your health.

Or the quasi-theological discussion

A: I'm not sure that it's right
B: Yeah, you religious guys say that about everything. It's fine. Get out of our way.

Not that this last piece is pro-life extension; the author employs an odd looking argument for choosing mortality based on the undesirability of cultural diaspora extended out ad infinitum. Seems a little strawman-ish to me, given the degree of cultural diaspora an earnest person can put under their belt in just a decade or two, but see what you think. The discussion in the comment section is worth investigating - join in if you feel you have a good counterpoint to add that hasn't been used already.

For my money, if the worst you have to complain about two hundred years from now is that you don't really understand 99% of the rest of (post-)humanity, I'd call that a stunning success in overcoming the many challenges ahead. Not dead, not frail, but healthy and engaged in living a growing, vital life.

Technorati tags: blogging, life extension

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I noticed a number of popular health articles on inflammation in the past week or so; current scientific thought on chronic inflammation, fat, and the onset of aging is on its way to widespread awareness. Here is an example of the type:

Controlling Inflammation Should be Part of Your Aging Management Routine

Inflammation, of course, is not all bad. In fact, as part of the typical immune response, it's essential for battling germs and healing wounds. The familiar redness, heat, swelling and pain from, say, a hangnail or a splinter are signs of inflammation at work.

But when the inflammation process fails to shut off after an infection or injury is over, trouble sets in. Many doctors now think persistent, low-level inflammation may pave the way for the chronic diseases of later life.

...

"No one would have thought these things were related," but they are, said Dr. Walter Willett, chairman of the department of nutrition at Harvard School of Public Health. The TNF connection also helps explain why obesity, particularly abdominal obesity, leads to diabetes. "Fat cells used to be thought of as storage depots for energy, as metabolically inactive," said Libby. "Now we know that fat cells are little hotbeds of inflammation - excess fat in the belly is a great source of inflammation."

"Aging management" in the same sense of "sliding down the gravel slope management," of course. There are better ways and worse ways, but it'll all end in tears unless science progresses rapidly enough to save us. Make no mistake, however: wrangling an extra decade of health our of our recalitrant biochemistry is quite possible for most folk. All it takes is the right lifestyle choices. That decade could make the difference between living to see the era of working anti-aging medicine - technologies that can meaningfully repair the biochemical damage caused by aging - or being dead just prior to this medical revolution.

All the science linking chronic inflammation with increased risk for almost any nasty age-related condition that springs to mind provides a very good reason to take better care of the health basics. Inflammation is, in effect, another form of wear on gears and cogs. Why run your machinery down and make your later life much shorter, expensive and more unpleasant when you don't have to?

Technorati tags: health, science

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Ben Best has been running modestly sized surveys of his end of the healthy life extension community and visitors to his website of late. I think that this is an excellent idea. While we all - hopefully - share a common desire to live longer, healthier lives, the community exhibits a wide diversity of viewpoints and goals. As in many smaller cultures, getting anything meaningful accomplished is often a matter of herding cats - so it can't hurt to get a better handle on where the weight of opinion lies in our growing community. So many new supporters and interesting parties have joined and contributed in recent years that the old assumptions and community knowledge are losing their relevance.

Here is Best's latest, via Cryonet:

The "production version" of my Life Extension Values Clarification Survey is now on my website:

http://www.benbest.com/lifeext/LE_Survey.php

I believe that this survey is a good tool for promoting life extension and cryonics by causing people to re-think their assumptions or raise their consciousness about issues they had not considered.

I request/suggest that cryonicists and life extensionists post the survey URL to the relevant (health, life-extension, etc.) newsgroups, discussion lists, chats, websites, etc., and/or send in e-mail messages to acquaintances as a means of raising awareness about life extension and cryonics. If you have not taken one of the earlier surveys you might want to try it, but otherwise there is not much point in doing so again.

This new survey has already been posted to my website for a few weeks and as of this writing has just reached 100 respondents:

http://www.benbest.com/lifeext/Display_LE_Survey.php

The responses can be compared to my earlier surveys of cryonicists

http://www.benbest.com/sandbox/Display_Survey_7.php

http://www.benbest.com/sandbox/Display_Survey_8.php

Jump right on in.

Technorati tags: activism, cryonics, life extension

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The mechanisms governing stem cell differentiation are complex indeed, but deciphering this biochemistry is the key to controlling cells for tissue engineering and regenerative medicine - producing replacement tissue on demand, and eventually creating totipotent stem cells on demand. Here is a selection of recent articles on step by step progress in this area:

Scientists announce stem-cell discovery

The scientists say the imprints, or "signatures," appear near the master genes that control embryonic development and probably coordinate their in the early stages of cell differentiation. Not only do the findings help to unlock the basis for embryonic stem cells' seemingly unlimited potential but the researchers say they also suggest ways to understand why ordinary cells are so limited in their abilities to repair or replace damaged cells.

"This is an entirely new and unexpected discovery," said Brad Bernstein, lead author of the study, an assistant professor at Harvard and a researcher in the Chemical Biology program at the Broad Institute. "It has allowed us to glimpse the molecular strategies that cells use to maintain an almost infinite potential, which will have important applications to our understanding of normal biology and disease."

How embryonic stem cells maintain their identity

The results also add to the team's earlier finding, reported in Cell last year, that a trio of transcription factors--Oct4, Sox2, and nanog--are key regulators of embryonic stem cells' pluripotency and self-renewal," he said. Pluripotency refers to the cell's ability to develop into multiple cell types. The three factors apparently work together to activate pathways critical for stem cell identity, while repressing those leading to differentiation.

Notch Promotes Neural Lineage Entry by Pluripotent Embryonic Stem Cells

Pluripotent [embryonic stem (ES)] cells should be a valuable source of neural cell types for cell biological investigation, neurodegenerative disease modelling, pharmaceutical screening, and possibly even regenerative therapies. If ES cells are to be harnessed effectively for these goals, it will be necessary to develop robust methods for directing neural commitment and suppressing differentiation into other lineages. In this study we have presented evidence for an unsuspected role of the Notch signalling pathway in promoting and directing primary fate choice in ES cell differentiation. Activation of Notch thus emerges as a key tool for steering ES cells toward the neural fate and away from nonneural fates.

If you're up for light scientific literature, the Notch paper above illustrates the real complexity in the study of cellular biochemistry: cells talk to and influence one other. Put a bunch of cells together, and they'll respond in all sorts of interesting, emergent ways to the introduction of biochemical signals of differentiation, signalling between one another all the while.

Furthermore, even at standard cell densities, 5% to 10% of cells still resist differentiation. This is approximately half the number observed for control cultures but nonetheless raises the question why do some ES cells elude neural commitment?

...

In the developing embryo, neighbouring cells must continually communicate with each other to coordinate patterning of tissues. Notch signalling patterns tissues by at least two types of mechanism. Lateral inhibition mechanisms ensure that neighbouring cells follow different fates, so that one single cell type does not dominate within a particular region. Lateral induction, a form of community effect, acts in the opposite way to ensure that cells within a particular region adopt the same fate choice. In the context of neural induction from ES cells, our findings indicate that Notch signalling acts to amplify and consolidate neural specification.

The complexity is enormous; researchers must develop better methodologies to work with very complex situations in order to keep up the rate of progress in biotechnology and medical science.

Technorati tags: biotechnology, stem cell research

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Barron's latest cover article - subscription only, thus ensuring it fails to become widely discussed or relevant to online discussion - takes a look at healthy life extension and the advance of science:

Science is getting closer to winning the war on aging, thanks in part to advances in genetics and nanotechnology -- and the vision of maverick scientists. But how many of us will follow a near-starvation diet to make it to 125?

You can probably infer the tone from that soundbite, but fortunately there are always people who can report more directly. Uglychart has a couple of direct quotes, such as this one from nanotechnology researcher and healthy life extension advocate Robert Freitas:

"There are many, many different components of aging and we are chipping away at all of them," insists Robert Freitas, a senior research fellow at the Institute for Molecular Manufacturing, a nonprofit, nanotechnology group in Palo Alto, Calif. "It will take time and, if you put it in terms of the big developments of modern technology, say the telephone, we are still about 10 years off from Alexander Graham Bell shouting to his assistant through that first device. Still, in the near future, say the next two-to-four decades, the disease of aging will be cured."

More from Mary Robinson at CRON Diary:

This week's issue had [calorie restriction (CR)] on the cover and Aubrey De Grey inside! The long article was about anti-aging research. It was not especially complimentary about either CR or Aubrey.

...

I am curious to see if Aubrey gets any contributors to the mprize from this. When I saw the article at first, I thought this would be a likely result. Rich guys read Barrons. $1000 a year is nothing to them. But, I don't think the article mentioned the mprize. I know Aubrey is very purposefully on a publicity campaign to increase public acceptance of longevity research and curing aging. I think this is a great thing. It's a tough sell though. I don't think Barrons was sold.

Barrons is for investors and pretty much decided that it was too early to think about investing in longevity.

Institutional investors - even the risk takers - are about the most conservative folk you're likely to find. Investing in medicine in the present highly regulated environment is simply not a good deal when compared to most of the other options on the table. Venture capitalists will take on any sort of risk except for political and regulatory risk.

From the very limited perspective of venture or market capital investment, it is pretty early to be looking at investing in anything but the groundwork for longer, healthier lives. From the broader perspective, however, we should all be investing in those organizations that encourage and fund serious longevity research. We are standing at a cusp - the early science is visualized, the infrastructure can be built, the scientists brought on board. But it will take a philanthropic investment in time and resources to get this off the ground.

Technorati tags: investment, life extension, media

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Ronald Bailey gets it (of course):

Earlier this month, some of the world's leading researchers on aging issued an open letter calling for more funding and research directly into the underlying mechanisms of aging and methods for its postponement.

...

Setting aside the question of funding, what makes this letter very important is that it signals the beginning of a shift in the research paradigm from trying to fix the diseases caused by aging to the broader goal of devising therapies to prevent the deterioration of aging in the first place.

The Scientists' Open Letter on Aging Research is at least as big a step forward for the culture of aging research as the Longevity Dividend proposal. This for the reason given by Bailey above, but also because the Open Letter stands as an inspiring example of scientists speaking out about the plausibility of extending the healthy human life span. Public dialog is the way to overcome conservatism in gerontology, overcome conservatism in funding organizations, and turn longevity research from the instant-death third rail of grantsmanship into a viable career choice and well funded field. This is the way to set the stage for the growth of a research infrastructure and community aimed squarely at healthy life extension.

So far, the Open Letter hasn't attracted the press attention it deserves. This is where folk like you and I come in; we all know of at least one journalist who writes on health or scientific research. Find their contact information and send a polite pointer to the Open Letter. Mention that it's a big step forward for aging research - the article practically writes itself.

Technorati tags: activism, aging, gerontology, life extension

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You might recall work published last year that suggested aging, non-responsive stem cells responsible for muscle maintenance and repair could be brought back into operation by suitable biochemical cues. Here is another relevant study:

Satellite-cell pool size does matter: Defining the myogenic potency of aging skeletal muscle

The deteriorating in vivo environment is thought to play a major role in reduced stem cell function with age. The capacity of stem cells to support tissue maintenance depends not only on their response to cues from the surrounding niche, but also on their abundance. Here, we investigate satellite cell (myogenic stem cell) pool size and its potential to participate in muscle maintenance through old age. The numbers and performance of mouse satellite cells have been analyzed using molecular markers that exclusively characterize quiescent satellite cells and their progeny as they transit through proliferation, differentiation and generation of reserve cells. The study establishes that abundance of resident satellite cells declines with age in myofibers from both fast- and slow-twitch muscles. Nevertheless, the inherent myogenic potential of satellite cells does not diminish with age. Furthermore, the aging satellite cell niche retains the capacity to support effective myogenesis upon enrichment of the mitogenic milieu with FGF. Altogether, satellite cell abundance, but not myogenic potential, deteriorates with age. This study suggests that the population of satellite cells that participate in myofiber maintenance during routine muscle utilization is not fully replenished throughout life.

Stem cell research is very much a field of change, like everything touched by modern biotechnology. The influx of new information is rapid indeed, which should mean that any debate that can be solved by learning more will be short and sweet. Can we rejuvenate aging stem cells, or do we just need to replace them? Or both? At the present rate, we'll probably know the detailed answer to that question by the end of 2007 - and possibly the answer to "how do we do it?" as well.

It is interesting to speculate on the sort of cell therapies that will be developed to repair the damage that aging inflicts upon us - intermediary therapies, really, that will be developed and used prior to technologies capable of preventing this damage from occurring, or repairing it in situ as it happens. It is not unreasonable to look at the state of stem cell science, bioinformatics and gene therapy today and predict that medical researchers of 2020 will be culturing new stem cell populations for individuals, correcting age-related damage to genetic and cellular material before returning the new cells to the body.

Technorati tags: stem cell research

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The Immortality Institute community is gearing up to produce a second book of essays, following up on the earlier publication of The Scientific Conquest of Death. The Institute has issued a call for abstracts with a June 30th deadline, and provides some suggested examples for theme and topic:

In 2004, the Immortality Institute, a registered not-for profit, grassroots organisation, published its first book, "The Scientific Conquest of Death", an anthology of essays on the science and philosophy behind a potential drastic extension of lifespan. The book has been a good success for the Institute. After the initial investment was recouped from sales, an electronic version was placed on the web last year, in order to maximise education and outreach potential.

In 2006, the Institute is seeking to publish a second book. Themes that were initiated in the first edition will be pursued further, new issues will be raised and new voices will be heard.

...

The following themes have been identified as of particular interest. However, the themes are strictly suggestions. Authors should feel free to suggest their own ideas.

A. Science, Medicine & Lifestyle

• the first books addressed the scientific life extension strategies of stem cell therapy, nanomedicine, cryonics and neuroimaging. We would like to invite contributions that expand on these topics, while remaining accessible to a lay audience.

• we seek contributions on scientific strategies that were not specifically addressed in the first book, e.g. gene therapy, transplantation, nutrition.

• an essay that critiques the SENS approach as a whole or in an aspect.

• an account of on caloric restriction from the perspective of the practitioner, that addresses the scientific background and the human side of such a diet.

• the scientific conquest of death has sometimes been linked with the assertion that it requires the development of advanced artificial intelligence. Rarely has this link been explained explicitly. We are looking for an essay that explains the relationship.

• an account of the human side of cryonics or an insiders account of cryonics emergency procedures in practice.

• a short essay on survival skills in a modern society.

B. Social Science, Philosophy & Literature

• an essay on the spiritual aspects of the quest for immortality, either as an academic analysis or by giving an overview of a number of "esoteric" alternatives to scientific life extension.

• a short story dealing with life extension, preferably science-fiction but not too far removed from current science and society.

• a historical account of an aspect of life extension, preferably from an author who was present at these events or has talked to witnesses who were.

• a sociological account of the life extension "scene".

• a perspective from a "veteran immortalist" – someone who has been actively interested in the science of radical life extension for 40 years or more.

• an essay that deals with the assertion that life extension will lead to overpopulation. As this is probably the most frequent concern raised in relation to the issue, submissions specifically addressing this issue will be given special consideration.

• an essay that addresses the concern that life extension is only for the rich.

While the Institute is, by its mission statement, in favor of life extension, we specifically and warmly invite all skeptics to contribute. As in the first book, there will be no censorship of critical voices and no rebuttals will be published without the original authors express permission.

The Scientific Conquest of Death was well received, and continues to be a useful tool for raising awareness of a future that includes the technologies of radical life extension. The Immortality Institute film project, Exploring Life Extension, has also proven its worth since its release last year. Based on this record, I expect the Institute volunteers and contributers to turn out another quality product - I recommend involvement to the writers in the audience.

Technorati tags: life extension, writing

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Volume 9 issue 1 of Rejuvenation Research is up for perusal and your general edification - don't forget that the previous issue is presently free and open. Interestingly, the journal publisher is running an ad for Aubrey de Grey's GENcast interview from some weeks back (scroll down on that page to see it). The publisher's overview blurb is becoming more glowing too:

Aubrey de Grey, at the helm of this multidisciplinary peer-reviewed journal, seeks to understand and ultimately defy the mechanisms of aging. He was featured in a recent 60 Minutes segment titled "The Quest for Immortality"; in a cover story on de Grey, MIT's Technology Review said, "His tireless efforts...have put him among the most prominent proponents of antiaging science in the world. ... De Grey has become more than a man; he is a movement."

Dr. de Grey and his outstanding international editorial board have the opportunity to further explore and advance the science, and perhaps achieve the ultimate goal of slowing or reversing the process of aging.

Someone in their marketing group has apparently decided to make this a project. But back to the scientific highlights from the latest issue:

Analysis of Telomere Length and Telomerase Activity in Tree Species of Various Lifespans, and with Age in the Bristlecone Pine Pinus longaeva

Normal somatic cells have a finite replicative capacity, and with each cell division telomeres progressively shorten, unless the telomerase enzyme is present. The bristlecone pine, Pinus longaeva, is the oldest known living eukaryotic organism, with the oldest on record turning 4770 years old in 2005. The results from our study of telomere length and telomerase activity [support the hypothesis] that both increased telomere length and telomerase activity may contribute to the increased lifespan and longevity evident in long-lived pine trees

Mitochondrial Dysfunction and Cell Senescence: Cause or Consequence?

The mitochondrial theory of aging remains to date one of the most popular theories of aging. ... Here, we review evidence supporting the involvement of mitochondria in replicative senescence and a possible link to telomere biology. Moreover, we suggest that this process might be more complex than originally formulated

Immunorejuvenation in the Elderly

Dysregulated T-cell–mediated immunity contributes materially to the increased susceptibility to infectious disease, and possibly cancer, in the elderly. One hallmark of this state of "immunosenescence" in humans is the predominance of large clones of peripheral T cells ... This excess of dysfunctional cells is indirectly immunosuppressive by filling the "immunologic space" and shrinking the T-cell repertoire for new antigens ... Therefore, it is hypothesized that deletion of such accumulations of dysfunctional cells would be beneficial to the individual.

Conjecture: Can Continuous Regeneration Lead to Immortality? Studies in the MRL Mouse

A particular mouse strain, the MRL mouse, has been shown to have unique healing properties that show normal replacement of tissue without scarring. The serendipitous discovery that the MRL mouse has a profound capacity for regeneration in some ways rivaling the classic newt and axolotl species raises the possibility that humans, too, may have an innate regenerative ability. We propose this mouse as a model for continuous regeneration with possible life-extending properties.

MRL mice have been attracting more attention in the past year, and the broader - but still nascent - field interested in recreating lizard-like regeneration is moving forward and getting noticed. Researchers are starting to make progress in understanding and manipulating the processes underlying the serendipitous discovery of regeneration in MRL mice - you can find a little more background back in the Fight Aging! archives. Personally, I'm skeptical that MRL-like (or salamander-like) mechanisms in mammals could on their own net you something approximating physical immortality, as seen in lower animals like the hydra. Mammalian regeneration - even impressive, standout, amazing mammalian regeneration - comes from the actions of stem cell populations, and stem cells in mammals have a sell-by date due to the accumulation of genetic mutations. After a certain point, you're looking at cancer and ever more cancer, no matter how well you can regenerate.

Technorati tags: aging, biotechnology, gerontology, longevity, medical research

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I'll say this for the younger adult crowd in the healthy life extension community: you 30 year olds are too damn optimistic about future timelines for healthy life extension technologies.

The biggest concern for me--right now, anyway--isn't maintaining my body in a youthful state. While this is definitely a concern, I feel able to adequately take steps in this direction, and mainstream society largely facilitates and encourages this behavior with widespread access to information and products aimed at youth restoration and maintenance. While many of these products are dubious, and others have only minor effects, I believe in the bridge hypothesis expounded by Ray Kurzweil, Aubrey de Grey and others: Each generation of life-extending interventions need only keep me alive until the subsequent generation in order for me to have an effectively indefinite lifespan. And given that I'm 29 and as far as I know in good health, I believe that, barring an unfortunate accident, there is a good chance for me to stay biologically youthful for a long period of time. (And yes, as a backup plan I am pursuing cryonics.)

I can't fault Simon Smith - the writer of that piece - for failing to stand up and do something; he has achieved more than I in building a well-trafficked megaphone and watering hole for healthy life extension and other transhumanist ideas. But still, there is the undercurrent of complacency that I see in the writings of many of the younger set - that the future technology is sorted, on the way, and meaningful anti-aging technologies will arrive in time.

I'd be optimistic myself if a scientific healthy life extension infrastructure as dedicated, large and advanced as that for cancer or Alzheimer's research actually existed. But it doesn't, and the scientific and advocacy communities have barely even started on the long road to building such a thing. The process could have been started a generation ago, but it wasn't. It may not get off the ground this generation.

My point here is that widespread complacency will be an undoing for us all - it's a common failure mode for those who look towards a better future, but never manage to engineer it. Massive assignment of time and resources is required for the goal of healthy life extension in our lifetimes. Engineering this use of resources is a huge task in and of itself. But supporters become enthusiastic, overestimate the degree of progress and the number of people helping make a better future, and stop making their own contributions. That scenario repeated en mass would mean that no progress is made - that healthy life extension technologies will not become effective enough to reach actuarial escape velocity within our lifetimes. Thus, game over; oblivion or taking your chances with cryonics.

We have a chance, a shot at radical life extension. We have to contribute, all of us, or it will slip from between our fingers.

Technorati tags: activism, life extension

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The Toronto Transhumanist Association recently hosted a talk on cryonics, the practice of low-temperature storage of the body and brain after death. Cryonics is an educated gamble on the capabilities of future medicine, and the only sensible, scientific chance at a longer life for all too many people who will not live to see the coming era of working anti-aging medicine. You'll find details and an MP3 of the event at Sentient Developments, and some follow-on thoughts at Betterhumans:

Another issue brought up at the meeting was the 'right to death' issue. While on the outside it might seem antithetical for a hopeful cryonaut to endorse voluntary euthanasia, it is in fact an issue that is very pertinent.

Suppose you come down with Alzheimer's. As someone who hopes to preserve their brain in the most pristine manner possible, the thought of undergoing an illness that rots away at your most precious resource should be frightening to say the least. Consequently, it could be argued that it should be within your rights to commit suicide prior to the point where Alzheimer's irrevocably starts to damage your brain.

So, as I've argued before, fight for your right to die.

I've discussed this before; cryonics requires the freedom that comes with strong property rights, including the right to do as you see fit with your most fundamental possession - your body. Sadly, none of us really have that right today:

For example, it is extremely difficult to choose the time and method of your own death, even under the most compelling circumstances. Assisted suicide is illegal in many countries, leaving terminal stage patients - who often endure intolerable pain and loss of dignity - with no options other than to suffer. Cryonics patients often want to die in a time and manner of their choosing, in order to best preserve their brain for cryosuspension. The US legal system prevented a patient with a terminal brain tumor from being cryosuspended before the tumor could damage his brain beyond repair. I am at a loss to explain why courts, laws, and plain old other people should have any say in these matters. If you don't own your body and your life, what do you own?

It is unfortunate that we live in a society in which people serve laws, as opposed to the other way around.

Changing gears, an interesting and positive profile of an Alcor member showed up online in the past few days:

According to the company, the cryogenic process is expensive, starting at $80,000 for the preservation of a brain and jumping to $150,000 for a whole body. Clients usually start a life insurance policy that, when it matures, gives money to Alcor rather than to family members.

Marshall Reaves, a 21-year-old ASU student, is in the process of taking out such a policy, which he says will cost him between $10 and $20 a month.

"For the price of a few drinks from Starbucks every month, I can potentially prevent myself from dying," Reaves says. "It's a matter of priorities."

...

"No offense to anyone else," he says. "But having my body frozen for the possibility of resuscitation doesn't seem any weirder to me than being burned or buried in a wooden box six feet underground."

...

"At this point in my life, I can't imagine ever wanting to die," he says. "When there are so many problems in the world, why wouldn't you want to have time to try and help solve them? Maybe my point of view will change over time, but I don't know. There's so much I want to do, and I'd be upset if I missed out on any of it."

That would be about right. Personally, I'd like to avoid the requirement of cryopreservation if possible - just as any sensible person would rather avoid suffering prolonged incapacity, no matter how reversible - but it's an infinitely better option than oblivion.

Technorati tags: cryonics

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A recent note in SAGE KE speaks for those scientists who, by the sound of it, would rather that the cut and thrust of unpleasant reality and conflicting viewpoints did not intrude upon their ivory tower. The unpleasant reality in this case is the mass suffering and death caused by aging, and the conflicting viewpoints are those debating whether more than 100,000 age-related deaths each and every day provides an imperative worth shaking things up over.

The second Strategies for Engineered Negligible Senescence conference (SENS II) featured some very provocative ideas. The explicit objective of extending human life span indefinitely has opened a large rift between the meeting's organizer and those who believe he is acting unscientifically, perhaps recklessly. Two SENS conference participants present their views on the divisive nature of SENS.

...

The legitimacy of the SENS approach and the media-friendly face provided by its originator came under attack once again in a multiauthored critique in EMBO Reports. Positing that the SENS agenda is "so far from plausible that it commands no respect at all within the informed scientific community," these authors wish to "dissociate themselves from the cadre of those impressed by de Grey's ideas in their present state." This statement is both forceful and ambiguous. It can be read as the relatively benign wish to be placed in a nonoverlapping circle on the Venn diagram of who believes what in aging-related research, or it can be read as a more sinister threat of shunning the apostates. If the authors intended the latter, what are the requirements for admission into the shunned cadre? It could not be attendance at one SENS conference, for some of the signatories have attended. Would attendance at both suffice? Further, is it not possible to express interest in or contribute to some of the scientific objectives of SENS without being judged a SENS acolyte? The objective of eliminating insoluble cellular waste using a bioremediation approach is novel and may have merit in ameliorating the undesirable consequences of aging.

...

The TR SENS Challenge is frequently mentioned by Aubrey de Grey (indeed he has devoted an editorial to it in Rejuvenation Research, the journal of which he is editor). Half of the wager on offer in the $20,000 TR SENS Challenge derives from the Methuselah Mouse Foundation (which de Grey chairs), and whereas the TR Challenge and the Methuselah Mouse Prize (see "Rewarding Research") both offer cash prizes drawn from a common source, that is where the similarity would appear to end. They are both public relations gambits, but the mouse prize was designed to be won, the TR Challenge to be lost (where the definition of "lost," as determined by de Grey, would encompass situations in which the SENS concept withstood a scientific critique or was simply left uncontested). The mouse prize is without question a clever way of attracting public interest to aging-related research, and by extending the mouse life span its winner will have made a contribution to knowledge. The TR Challenge serves no purpose but to attract attention to Aubrey de Grey and the increasingly bitter dispute with his detractors. Although it allows him to taunt them (baselessly, given the way in which the criteria have been set), it is hard to imagine how this could be a positive thing for future SENS conferences, which are likely to become increasingly populated by media in search of controversial sound bites from its organizer. From all indications, they are likely to come away satisfied. Whether the same will still be said for attending scientists remains to be seen.

This misrepresents the purpose of the $20,000 SENS Challenge, but is indicative of the knee-jerk - and usually justified - hostility that many scientists have towards any sort of debate that falls outside the bounds of tradition. But better tactics than adherence to tradition are needed when the old guard turtles up and refuses to debate, the most effective of traditional tactics for defending intellectual vestment in a field undergoing rapid cultural or scientific change. Human nature is human nature, but no-one should feel entitled to a peace of mind that costs lives.

We've already established that quietly and politely advancing knowledge just isn't going to cut it when it comes to getting mainstream gerontology into gear - I for one feel no qualms about disrupting the quietude of an ivory tower or three in order to speed progress towards working anti-aging medicine. If the culture of biomedical and aging research was already up for getting on with finding a cure for aging post-haste, using the best possible methods available, then it wouldn't need the shock treatment. What is the point of advancing knowledge about aging and longevity in the absence of intention and urgency to use it to alleviate human suffering and death?

The scientific method will not suffer for groups making their points forcefully and in public. No-one here is bypassing peer review or advancing crank theories. What we do have is an excellent example of the sort of fight that takes place over lifting the self-imposed blindness to the horrors of aging. Once you are forced to confront the reality of tens of millions of deaths each year, you are forced to confront the ethical imperative to do something about it - and do it as fast and as well as is possible.

Technorati tags: advocacy, gerontology, life extension, science

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There's nothing like a catchy headline: "Increased antioxidant capacity reverses some effects of aging". Reading the article shows that nothing of the sort is going on, of course. Antioxidants are indeed involved, but this is no more than the normal byplay of scientists attempting to figure out just a little more of mammalian biochemistry as it relates to aging:

The study is one of the first experiments to assess memory performance among aging mice genetically engineered with an abundance of an antioxidant enzyme called extra cellular superoxide dismutase. As this group of mice aged, they performed better on memory tasks and demonstrated cellular improvements in the hippocampus, a part of the brain required for memory.

Conversely, the same experiments in younger mice showed that high levels of the antioxidant were detrimental to memory function.

Previous studies have concluded that oxidative stress contributes to aging and aging-related impairments in memory. Klann conjectures that high antioxidant levels, within reason, could promote longevity and reduce the risk of dementia associated with normal aging and neurodegenerative disorders such as Alzheimer's disease.

Oxidative stress shows up as a part of the biochemistry of a wide range of neurodegenerative conditions - it follows that damping down that stress should help slow the progression of symptoms by slowing the destruction of cells. Slow is not reverse, however. In addition, this sort of approach doesn't actually address underlying causes at all, as recent research into Alzheimer's illustrates:

Dr. Atamna believes that the combination of functional heme deficiency, which harms mitochondria needed to produce energy, together with the increase in oxidative damage caused by the peroxidase, is what eventually kills the cell.

Increased oxidative damage to neurons - through increased activity of reactive oxygen species, or increased vulnerability to the same - is quite far down the chain of damage, failures and consequences.

There's nothing wrong with promoting your research, research that usefully adds to our knowledge of neurodegenerative conditions and their biochemistry, but keep it responsible. There is little chance that this sort of work will lead to any more than "finger in the widening crack in the dam" approaches to treating age-related neurogeneration - the old school approach of pumping chemicals into our systems to try and address end results of underlying damage is not the way forward. The new approaches of metabolic tinkering and optimization to minimize ongoing damage are not much better.

We must put more effort into addressing the underlying biochemical damage of aging - not just slowing its accumulation by tweaking the processes that cause damage, but actually stepping in to repair damage. This is a much more plausibly efficient way forward, whatever the details of its implementation - strike at the root, not the branches.

Technorati tags: life extension, medical research, SENS

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A conversation on concepts and views of radical life extension - and the steps to get us there - is underway over at one of Catallarchy's opposite days:

Shaky analogies seem to abound. [Radical life extension] is not like a ladder to the moon, because there's demand for it - once you've admitted that it's a tractable engineering problem and that people would pay a lot to get it, you're basically only quibbling over the timeline. [Radical life extension] is also not like [general artificial intelligence], because our understanding of intelligence is nowhere near our understanding of cellular biology - and I think you'd be hard pressed to contend that the former isn't a much harder problem than the latter.

In any case, you put the question correctly, almost: "whether we know enough now about human biology ... and have the technology or some outline of a possible realistic future technology to 'defeat' mortality." The only thing that's wrong with this is that last part. We don't need to "defeat" mortality in the next 60 years, just push it back far enough that some people alive now will then live long enough to see the day when it is effectively "defeated." It's perfectly reasonable to be skeptical that this will happen for people alive today, but it's also unreasonable to dismiss the possibility out of hand.

Make sure you read the lengthy comments, and feel free to dive in with your own thoughts on the matter. It is very gratifying to see more people intelligently discussing actuarial escape velocity, squashing the ever-dreadful Tithonus error along the way. As more folk talk around the issue, knee-jerk, mistaken viewpoints will fade and diminish as obstacles to advocates and fundraisers. Education is important for efforts to generate large-scale funding for anti-aging research, and like almost all important things, it works so much more effectively as a distributed, self-organizing process.

I rather look forward to the day when the cultural conversation on healthy life extension has grown so large and enthused that I could lay down this keyboard and no-one would really notice. We've a way to go yet, but that day is much closer than it was even a few short years ago.

Technorati tags: advocacy, life extension

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More coverage of the 4th annual Calorie Restriction (CR) Society conference is up in various locations around the web, including some from local media outlets. There will be more from the CR blogosphere to come later, no doubt, once people have had a chance to return home and wind down. Some excerpts are below, but there's too much to quote effectively; you should go and read the sources.

A first report from Mike Linksvayer

Conference co-organizer Robert Krikorian said he thought attendees expected less from calorie restriction, at least in terms of life extension, than did attendees at the first conference, held in 2001.

...

Luigi Fontana gave an update on human CR studies in progress that show CR practicioners have extremely low markers for cancer and heart disease risk and noted one study in which raw foodists had markers in some (but not all) areas as good as CR practicioners suggests that protein restriction may be something to study.

...

Aubrey de Grey suggested that the CR effect is mostly absolute and will not effectively scale for long lived organisms due to famines lasting a similar amount of time for organisms regardless of lifespan, resulting in only two or three years' increase in life span for CR'd humans.

Mary Robinson on CR research:

The amount of research is really very small, considering the potential value of CR. Funding is very hard to get. There is a lot of bias against longevity research.

The evidence from studies to date is pretty sketchy and inconclusive. You can interpret it many different ways. Several of the researchers there had a strong belief bias towards the hypothesis that they have invested considerable career resources in. I felt very agnostic compared to all of them. There was a lot of interesting debate.

...

To me there was a big gap between the "pathway" people and the old-style biologists. The "pathway" people were very systems-oriented and seemed comfortable with the complexity presented by the human body. They had ways to deal with it. The old-style people are just poking sticks at things to see what happens. Too, too slow. Too, too simple. However, two of the "non-pathway" people, Josh Mittledorf and Aubrey De Grey are pretty out of the box thinkers. They force people to re-examine their ideas. A very good thing.

UPDATE: More good stuff from Mary Robinson

Aging theorists (Aubrey De Grey, Josh Mitteldorf, Ed Masoro, Steve Austad) are not sure that CR will extend life in humans the way it does in other animals. It might - it might not. The animal evidence is complicated and somewhat contradictory. Traditional experiments on animals are somewhat "blunt instruments" - the results are so dependent on laboratory conditions and the animal's genetics. Evolutionary biology is so theoretical at this point, it can support many different conflicting hypotheses about human life extension.

...

I think the evidence strongly implies that CR will work in humans to extend life (disagreeing with Aubrey ). For it to have a short term effect - of only one season or two - as Aubrey De Grey suggested in his talk - he assumed that the CR effect would "turn off" after a year or two. Luigi's testing shows that it does not. His test results were remarkably consistent for people of many different ages and genetic backgrounds, on different diets, and on CR for different amounts of time. He claims that if you give him a blood test results for someone and he knows their age, he can say definitively whether they are on CR or not. There is no evidence that it turns off - even after a decade or more. And, the kind of gene expression changes in rats appear to be echoed in humans. The only question is whether there is something in humans that makes these changes ineffective in extending life.

CR Society members follow variations on regimen

"A large percentage of people enjoy the diet, but a lot of people would trade the diet for a pill," Calorie Restrictive Society president Brian M. Delaney said.

Restricted-calorie society finds better living through less eating

The society's philosophy — that slashing calories will lead to a longer, healthier life — has been supported by numerous scientific studies on rats and mice, which consistently show an extended lifespan when put on a diet of 30 to 50 percent fewer calories. A study sponsored by the National Institute on Aging published this week in The Journal of the American Medical Association also showed that reducing calories in 48 people for six months led to decreases in both body temperature and insulin levels, typically considered signs of longevity.

...

"A lot of the misery and decrepitude of old age is disease, conditions like Type II diabetes and cardiovascular disease," CR Society president Brian M. Delaney said. "A lot of people not on this diet at 58 absolutely would start getting Type II diabetes. We want to start promoting more research into how to implement the diet, or if an alternative can be created."

The evidence for calorie restriction as the best thing most of us could presently be doing for our long term health is overwhelming. CR is small potatoes in the grand scheme of what is possible through future medical science, however. This is even more reason to practice CR - it greatly increases your chances of living to see a future of working anti-aging medicine.

The debate over the degree of human healthy life extension provided by calorie restriction will no doubt continue into the era in which it doesn't matter anymore, unless a clever and widely accepted method of extrapolating the effects of CR on human longevity is developed first. The demonstrated, proven benefits to human health and resistance to age-related degeneration should be more than enough to convince you to give it a try, however.

Technorati tags: calorie restriction, life extension

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Two good articles from Ronald Bailey - author of Liberation Biology - have reached the press in the past couple of days; I recommend that you read both.

Anyone for tennis, at the age of 150?

By the end of this century, the typical European may attend a family reunion in which five generations are playing together. Great-great-great grandma, at 150 years old, will be as vital, with muscle tone as firm and supple, skin as elastic and glowing, as her 30-year-old great-great-granddaughter with whom she's playing tennis.

After the game, while enjoying a plate of vegetables filled with not only a solid day's worth of nutrients but medicines she needs to repair damage to her ageing cells, she'll be able to chat about some academic discipline she studied in the 1980s with as much acuity and memory as her 50-year-old great-grandson, who is studying it now.

...

The highest expression of human nature and dignity is to strive to overcome the limitations imposed on us by our genes, our evolution and our environment. Future generations will look back at the beginning of the 21st century with astonishment that some well-meaning and intelligent people actually wanted to stop biomedical research just to protect their cramped and limited vision of human nature. Our descendants will look back, I predict, and thank us for making their world of longer, healthier lives possible.

The Research Imperative

Americans, by their purchases in the marketplace and their advocacy in the halls of Congress for setting budget priorities, have already answered Callahan's question about the appropriate goals of medicine—full speed ahead with biomedical research! Americans are supportive of research aimed at curing the diseases of old age precisely because more of us get to our golden years. In fact, dying before age 75 is now considered by most Americans to be "premature." Even young people favor research because they realize that they will one day be old, so cures developed for old people now will be available for them when they need them. (Not to mention that some young people may actually like to avoid having their parents and grandparents disappear into the undiscovered country.) Also, spending on biomedical research, both private and public, enjoys widespread public support because health is something we, as members of a liberal pluralist society, can all agree is an essential precondition for anyone to pursue any of the diverse ends they think make for a good life.

Callahan despairs that the more healthy life Americans enjoy, the more we want. He inveighs against this "abolition of fatalism," nostalgically noting, "In the past we reconciled ourselves to aging and death because we could do nothing." He adds, "It seems to me that the whole trajectory of modern medical research has been basically to treat [death] as if it were an accident. As far as I know, there are no fatal diseases that the NIH (National Institutes of Health) finds acceptable. The NIH is not in favor of immortality, at least officially, but there are no diseases that kill people that it is prepared to tolerate."

Sounds about right to me.

There are any number of unsavory types in the world willing to tell you what you can and can't do with your own life - up to and including mandating the time and manner of your death. The misguided - and, frankly, evil - people who oppose progress towards healthy life extension will undoubtably lose. Eventually. Luddites are always overwhelmed by research and reality. Eventually. However, attempts to hold back progress can cause very real damage by slowing things down. In this modern age, this means enlisting risk-averse Western government, bioethics and related anti-progress movements to throw as many roadblocks in the way as possible. In the case of healthy life extension research, a day of delay means another day in which more than 100,000 people die and hundreds of millions more suffer the pain and disability of age-related conditions.

Many people in the transhumanist and futurist communities see radical life extension as inevitable. It is indeed inevitable given present rates of technological development - but not necessarily soon enough for those reading this post in 2006. We must work hard to ensure that our future includes access to effective anti-aging technologies, to ensure that the first healthy life extension medicine is developed in time to help us overcome age-related frailty, suffering and death.

The future is what you make of it. If you want to live a much longer, healthier life, then you must step up and do something to support and encourage appropriate medical research today.

Technorati tags: activism, life extension

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You'll find a brace of posts at the Scientist reporting on the Keystone meeting on stem cells held at the end of last month.

Stem cells: Ethics before science

Her conclusion? That stem cell scientists are not ethicists, but they have more knowledge about stem cell science, and therefore a duty to explain what they are doing to the general public.

Sending stem cells back in time

Scientists at the University of Central Florida have devised a creative way to obtain stem cells with embryonic properties -- by coaxing mesenchymal stem cells (MSCs) to return to their roots, and display embryonic qualities.

More reprogramming clues - maybe

One of the biggest holy grails in biology involves finding a means to generate pluripotent and infinitely replicating stem cells without generating an embryo. One Japanese team presented some potent clues last night at the Keystone conference on stem cell biology -- but stem cell researchers will need a few more bread crumbs before they can put this potentially exciting information to use.

Using the liver to make the pancreas

A series of experiments appeared to suggest that it might be possible to convert liver cells into pancreas cells using Pdx-1, which is essential for the formation of the pancreas. The researchers administered Pdx-1 to mice, and discovered little clusters in the liver that looked like beta cells, at which point they "got very excited," Slack said. However, they soon found similar clusters in the biliary system of untreated mice, which made things even more exciting -- it presented what they believe is the first evidence that mice may carry naturally-occurring beta cells outside of the pancreas.

Epi-embryonic stem cells?

Ursula Manuelpillai at the Monash Institute of Medical Research in Victoria, Australia presented a poster in which they detail the potential of human amniotic epithelial cells (HAECs) in the inner membrane that protects the fetus during pregnancy.

The researchers exposed HAECs to factors that nudge them to differentiate into cell types. Indeed, the cells displayed markers that suggest they differentiated into a variety of cells, such as astrocytes, neurons, hepatocytes, and pancreatic cells. "I'm not saying the cells are pluripotent, but they certainly have the markers of pluripotency," Manuelpillai told me.

Glimpses of stem cell medicine

In a study involving nearly 200 people blinded after burns depleted their stores of limbal stem cells, stem cell transplants corrected the vision of the majority of patients, even several years after the operation. Another man with epidermolysis bullosa (EB), a disease in which the slightest trauma causes major damage to the skin, received transplants of his own genetically corrected epidermal stem cells, and experienced major improvements in the areas that received the transplant.

...

Ronald McKay from the National Institutes of Health estimated that as early as within the next several months, researchers might obtain dopamine neurons from human embryonic stem cells -- a potentially major advance for people diagnosed with Parkinson's disease.

Interesting stuff, and good that the blogs were not put behind the great wall of paid registration when the gates closed once more.

Technorati tags: stem cell research, regenerative medicine

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With calorie restriction bubbling forth here, there and everywhere since the recent CALERIE study publications, the ever voluble MPrize volunteer April Smith is blogging the 4th annual Calorie Restriction Society Conference in Tucson, Arizona.

The night before:

I'm so excited to be going to the conference. It's 80 degrees in Tucson, lots of my friends will be there, the magnificent Aubrey de Grey will be in attendance, and my CR needs some rejuvenation.

Day one:

We shared a cab with Aubrey and legendary CR researcher Luigi Fontana and arrived just as the welcoming reception was going into full swing. It was wonderful to catch up with all my old friends from last time and also to meet new friends.

...

The thing I find most inspiring about the CR Conferences is that everyone here is enjoying life so much that they want to keep living, and are willing to do what it takes to do so. We're feeling great now, and we plan to keep on feeling great. We're looking forward to the dawn of radical bio-aging biomedicine, but we're taking control of our lives and health in the meantime. As Aubrey said, "The party is already starting."

The Calorie Restriction Society conferences are one of the more visible signs of collaboration and mutual support between the scientific and calorie restriction communities - the two sides coming together to get things done and make progress more effectively than either could alone. May it continue.

Technorati tags: calorie restriction

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The Singularity Summit at Stanford is coming up next month:

What, then, is the singularity? It's a future period during which the pace of technological change will be so rapid, its impact so deep, that human life will be irreversibly transformed. Although neither utopian or dystopian, this epoch will transform the concepts that we rely on to give meaning to our lives, from our business models to the cycle of human life, including death itself. Understanding the singularity will alter our perspective on the significance of our past and the ramifications for our future. To truly understand it inherently changes one's view of life in general and one's own particular life.

The Singularity Institute is the principal driving force behind the event, and as such you can expect a strong focus on general artificial intelligence (GAI) and Vingean or Kurzweilian views of the technological singularity. The interest here is, at root, in methologies for overcoming limits to exponential growth that result from the limits of the human mind. This is all of little direct relevance to the near future of healthy life extension and advancing medical technology - as it will take place while the development of GAI is still in its earliest stages - but it is of great relevance to the mid- and long-term future of all human endeavors. Tools that improve our ability to manage complexity will greatly speed the advance of biotechnology, a science that is already bumping up against the limits imposed by our ability to manage and understand vast datasets and complex biological systems.

The Singularity Institute is worth a closer look by those interested in successful advocacy for a cause. Their transformation from a force-of-will personal venture to professional advocacy and position group has been quite impressive since Tyler Emerson took the reins, culminating in acquiring Peter Thiel as an advisor and patron. I can't overemphasis the cachet that brings in monied circles; Thiel is widely regarded as having an excellent sense of what to invest in and where the technology world will be going next. Don't let that obscure the small, important details for you, however - take some time to watch how the Institute does things if you're interested in getting ahead in advocacy.

UPDATE: Tyler Emerson emails to note:

You wrote, "The Singularity Institute is the principal driving force behind the event,..." While that's partially accurate, this isn't an SIAI event -- it's a Stanford event organized by the Symbolic Systems Program, and co-sponsored by the Singularity Institute, KurzweilAI.net, and the Stanford Transhumanist Association.

You might note that Thiel became involved in part because he was very impressed by our vision and objectives, and especially by Yudkowsky's work. As it stands, the post could be interpreted as if I were solely responsible for Thiel's involvement, which isn't accurate.

The Singularity Institute seems set to successfully emulate the Foresight model in bringing interest and investment into their field, and the best of luck to them. Now if we could just garner a few more organizations like that for the healthy life extension cause to complement and compete with the Methuselah Foundation...

Technorati tags: advocacy, AI, singularity

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A thought from Glenn Reynolds:

people once looked to supernatural sources for such now-mundane things as cures for baldness or impotence, only to find those desires satisfied, instead, by modern pharmacology. Yet that hardly makes those who place their faith in pharmacology members of a religion -- or, if it does, it makes them members of a religion that is distinguishable from those dependent on the supernatural. ... How do we know that people want the kinds of things that advanced technology is supposed to offer? Because they've been trying to get them through non-technological means for all of recorded history.

Reynolds was discussing a Kurzweilian technological singularity - and a sudden surge in folks making the invalid comparison of serious futurism with religious belief - rather than radical life extension, but it's all very applicable. New technology is the way that you accomplish things you were previously incapable of accomplishing. Religion and myth are reflections of what most people want to accomplish, or find attractive. We should expect the near future that we build to echo our most fundamental desires; the only reason the present falls short is our lack of ability.

It's common in business circles to find that people say one thing in your surveys and then go on to do quite another, but the rich history of effort and expenditure in search of ways to prolong the healthy human life span shows that those first to market with working, demonstrated, effective anti-aging medicine will be well rewarded. That incentive, not altruism, is the bottom line driving any group towards achieving this goal - so we should be glad that the underlying will and desire is so broad, even if it is oftimes filtered through ignorance, confusion and distraction.

Technorati tags: life extension, singularity

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The processes of inflammation are a potent source of age-related cellular damage, as this first article reminds us:

Chronic inflammation spurred by an immune system run amok appears to play a role in medical evils from arthritis to Alzheimer's, diabetes to heart disease. There's no grand proof of this "theory of everything." But doctors say it's compelling enough that we should act as if it were true -- which means eating an "anti-inflammatory diet," getting lots of physical activity, and losing the dangerous, internal belly fat that pumps out the chemicals that drive inflammation

...

Chronic inflammation is so similar in different diseases, Libby said, that when he lectures, he uses many of the same slides, whether he's talking about diseases of the heart, kidneys, joints, lung, or other tissues.

Only a few years ago, heart attacks were explained as a plumbing problem -- blood vessels that became clogged with atherosclerotic plaque as "bad" (LDL) cholesterol was deposited on vessel walls. Now, doctors know that this bad cholesterol gets embedded inside artery walls as well, where the immune system "sees" it as an invader to be attacked. The ongoing inflammation in arteries, essentially a revved up immune response, can eventually damage arteries and cause "vulnerable" plaque to burst. It is because inflammation is now seen as such a hallmark of heart disease that many doctors use a test for inflammation called CRP to help assess a person's cardiac risk.

It's long been known that type 1 diabetes is linked to inflammation -- the body's immune system attacks the cells that make insulin. Now, new research is suggesting that type 2 diabetes, the kind that generally sets in in adulthood, often begins with insulin resistance, in which cells stop responding properly to insulin. Doctors now know that during chronic inflammation, one of the chemicals released is TNF, or tumor necrosis factor, which makes cells more resistant to insulin.

""No one would have thought these things were related," but they are, said Dr. Walter Willett, chairman of the department of nutrition at the Harvard School of Public Health. The TNF connection also helps explain why obesity, particularly abdominal obesity, leads to diabetes. "Fat cells used to be thought of as storage depots for energy, as metabolically inactive," said Libby. "Now we know that fat cells are little hotbeds of inflammation. Excess fat in the belly is a great source of inflammation."

Autoimmune diseases like rheumatoid arthritis are also believed to be linked to inflammation. In arthritis, for instance, inflammatory cells called cytokines lead to the production of enzymes that break down cartilage in joints.

Inflammation also plays some role in Alzheimer's disease, said Linda Van Eldik, a neurobiologist at the Northwestern University Feinberg School of Medicine.

Whenever the brain is injured or infected, cells in the brain called glia pump out cytokines. Normally, this response shuts down when the injury or infection is over.

"But in chronic neurodegenerative diseases like Alzheimer's, these glial cells are activated too high or too long or both," Van Eldik said. The plaques and tangles in patients' brains attract the attention of glial cells, making them pump out even more cytokines to try to repair this damage and creating chronic inflammation.

Age-related diseases are the final breakdown of a system that has suffered a great deal of cellular, genetic and biochemical damage. Just like any complex machinery, it will break down more rapidly if subject to a higher rate of ongoing wear - such as that provided by inflammatory processes. As scientists uncover and catalogue ever more of our biochemistry, common sense health advice (exercise, stay trim, eat a good diet, take supplements) generally turns out to minimise exposure to chronic inflammation - especially losing the excess fat.

Technorati tags: health

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It seems Mary Ann Liebert, Inc. has noticed that one of their journal editors is getting a fair amount of press attention of late - it never hurts to get in on the act when you're in the publishing business. I had missed the opening of the December 2005 issue of Rejuvenation Research to all for free; you should take the time and have a look. Some highlights:

From the Editorial (PDF):

For the past five years, I have been refining and promoting an approach to life extension termed "Strategies for Engineered Negligible Senescence" (SENS). SENS differs from other approaches (such as antioxidants, hormesis, or calorie restriction mimetics) in two main ways: firstly it is an approach to reversal (repair) of eventually pathogenic age-related changes ("damage"), as opposed to the retardation of their further accumulation, and secondly it is a piecemeal approach, in which the various types of such damage are addressed individually, rather than being simultaneously combated by the downstream effects of a single "magic bullet." Most biogerontologists appreciate that aging is bad for you and should be postponed as much as possible, as soon as possible, just like any disease. They are as aware as anyone of the scale of the sociopolitical consequences of even modest success in this, but they possess the sense of proportion so lacking in society at large on this matter and conclude that we should save lives first and deal with the consequences as they arise, just as when we almost eliminated infant mortality a century ago.

NANOG Changes in Mouse Kidneys with Age:

NANOG is essential for mouse and human embryonic stem cell (ESC) pluripotency and selfrenewal. ... These data suggest that the kidney has its own cells expressing NANOG, and loss of NANOG expression occurs in an age-dependent manner in the kidney, either due to developmental factors or aging, particularly in renal papillary tissue.

Reviewing "Ten Good Questions" (PDF):

Belshaw's arguments, then, would only be persuasive to someone unfamiliar with the Epicurean position. His failure to undermine this position, however, illuminates something interesting about it that might be overlooked. I mentioned earlier that if death was not a harm this might reduce the reasons one had for developing life extension technologies. Yet it now transpires that even if death is not a harm one still might have good reason to pursue such technologies, given that the extra life that they would provide would be enjoyable to those who experience it. The issue of death's goodness or badness to the one who dies, then, is orthogonal to the question of whether one should pursue such technologies.

Reporting on the 11th IABG Congress (PDF):

How far, then, are we from serious life extension in mammals and eventually in humans - and in particular, how far are we from life extension that merits the term "biomedical" by virtue of being applicable to those who are already on the slippery aging slope? IABG11's organizers are well known to be skeptical of my views of how, how much, and how soon aging can be postponed, so I was grateful for the invitation to outline my position in the last session of the conference, which was gratifyingly well attended despite occurring on the morning after the excellent conference banquet. I was able to draw attention to the just-announced SENS Challenge and was suitably pleased to see no one volunteering to submit an attempt to win the $20,000 on offer. If it is still unwon by the time of IABG12, in Greece in 2007, I suspect the skeptics will by then be fewer in number.

Technorati tags: aging, gerontology, life extension

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A discussion on the prospects for various age-groups making it into the era of actuarial escape velocity and radical life extension is presently underway at the revamped Betterhumans. This should be a topic near and dear to anyone with an interest in long-term health; what new medical technologies and capabilities will come onto the market in the decades ahead, and how will this affect our longevity? Investments in research are made and withheld on the basis of this sort of elementary futurism, and therein lies a feedback loop that we can influence to the benefit of all. Some highlights:

I believe Transhumanism is infused with a great deal of focus on the matter of self-preservation of the individual at all costs (some consider this highly selfish) and the painful reality may very well be that our generation was simply born too early and we will be among the last to fall before the Grim Reaper of our presently very limited biology.

What are our odds of making it??

...

I don't think there is any way to estimate "our chances" as a group. I think that different individuals have varying "chances" of making it, determined by the variables of their individual lives. I think it's highly probable that someone presently in their thirties, somewhere in the world, will achieve an extremely long life -- much longer than 120 years.

...

I am in my 30's and we live in a world of increasing technological progress. My grandfather lived in a farmhouse and did not have central heating, used gas lanterns for light and before he died at 91 in 2001, he used ATM machines, credit cards, had central air conditioning, and used a VCR.

I do not know if I will make immortality, but I am (perhaps overly) oppomistic that we will make key advances that allow our generation to live longer and better than our grandparents and parents.

...

If you for one instant don't think a caloric restriction memetic will be on the market within 40 years... you are OVERLY pessamistic.

Its all about bridges. Stem cells, gene therapy, life extension drugs all keep up from the grim reaper.

In those 20 years, more breakthrus will take place. and I might get another 20 years. And again, and again.

...

I hate to demolish your comforting illusions, but to save anyone alive, every member of this community needs to work very hard, starting now, and be very lucky on top of that.

This last point is closer to the mark. We must not passively wait to see what happens - that's a very good way to wind up in the sort of future you don't want to see, suffering from age-related conditions that could have been cured. "If only" is poor help after the time to act has passed, and it is by no means certain that the right investments in research will be made in the years ahead. Right now, for example, nearly all of the very modest funding for relevant research goes to comparatively ineffective ways forward.

What are the odds? Better to ask how we can shape the odds - the future is what we make it to be. In these early years of the biotech century, folk like you and I can make a great deal of difference to the future of meaningful anti-aging research. We can write about it, talk about it, raise awareness and educate our peers, support forward-looking advocacy, encourage scientists towards better research strategies and set the first rocks in the avalanche on their way downslope.

Technorati tags: activism, advocacy, life extension

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