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

Posted by Reason at 4:25 PM
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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

Posted by Reason at 10:37 PM
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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

Posted by Reason at 10:51 PM
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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

Posted by Reason at 10:56 PM
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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

Posted by Reason at 9:38 PM
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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

Posted by Reason at 7:16 PM
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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

Posted by Reason at 9:27 PM
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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

Posted by Reason at 10:07 PM
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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

Posted by Reason at 7:37 PM
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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

Posted by Reason at 10:13 PM
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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

Posted by Reason at 10:04 PM
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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

Posted by Reason at 10:08 PM
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