Stepping Up To Make a Difference
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There's nothing quite like putting your money where your mouth is. It's something that more advocates and volunteers supporting healthy life extension are going to have to do in order to accelerate progress in advocacy, education and public awareness. I'm very pleased to see this initiative on the part of Mark Patterson:

As most of you know I've founded Big Picture Tours for one reason: to fund rejuvenation research. For now, 100% of this focus translates to supporting the Mprize for rejuvenation and longevity research.

Big Picture Tours combines advanced Internet technologies with our own proprietary server-side ClientSmart(TM) technology to deliver bezel to bezel full-screen presentations of unmatched photographic quality. Our server side technology detects the client aspect ratio, connection speed and operating system and then streams a presentation (choosing among 18 versions) best suited for the client.

The result is that businesses and organizations are able to "tell their story" over the Internet in ways never before possible.

Some of you operate your own businesses and could benefit from this technology, others may work for businesses that could benefit. For the first twenty projects referred through contacts on the Mprize list or any Mprize 300 member, Big Picture Tours is offering to donate all revenues above our cost. This will translate to thousands of dollars donated directly to the Mprize. Please contact me at Mark@BigPictureTours.com for further details.

Below is a link to 4 of our recently completed projects so that you can see the quality of our work first hand. Once you've got a show running, right click and select "Full Screen".

http://www.BigPictureTours.com/GreatestHits.aspx

A very good job; that's something for the rest of us to top - and to spread the word about.

Understanding Apoptosis
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Since we're talking about cancer today, it is worth pointing out some new science on apoptosis, the process of programmed cell death. The relationships between aging, cancer and the biochemistry of cellular life span are complex (to say the least), but there is something to be said for starting with the most basic basics and working up to the big picture. "We think this gene will really be a hot spot in research ... The life and death of cells is a complex avalanche of reactions, controlled by a few molecules that sit atop a biochemical 'pyramid.' ... We think these findings are very significant. This is the first enzymatic step that regulates the degradation of proteins that control cell death."

Link: http://www8.utsouthwestern.edu/utsw/cda/dept37389/files/230609.html

More On Cancer Stem Cells
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Cancer is one of the many common age-related conditions that must (and will) be defeated if any healthy life extension technology is to work - there is no sense in living longer only to be riddled with cancers. In many ways, it is the most important of all age-related conditions, since it is so intimately entwined with the biochemical mechanisms of aging and cellular repair. Research into cancer illuminates aging, and vice versa. The discovery of cancer stem cells is a promising step forward in the fight to cure cancer - it will lead to much more effective, efficient therapies with fewer side effects. This Nature article is an example of the sort of progress that can be made with greater understanding.

Link: http://www.nature.com/nature/journal/v435/n7046/full/4351169a.html

Killing Cancer With Progeria
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You may recall that scientists cracked the secrets of Progeria - an accelerated aging disorder - in 2004. This Reuters AlertNet piece details some of the follow-on work: "In 2003, a team of [scientists] found that progeria was caused by mutation in a protein called Lamin A, which lines the nucleus in human cells. ... mutated Lamin A actually disrupted the repair process in cells, thus resulting in accelerated ageing. ... the enzyme Zmpste 24 was responsible in converting prelamin A to functional Lamin A. Zhou's laboratory is now developing inhibitors to Zmpste 24, which he hopes to apply to tumours. These inhibitors should theoretically disrupt Lamin A production, thwart the repair function in cancer cells, and bring on their premature aging and death."

Link: http://www.alertnet.org/thenews/newsdesk/HKG81160.htm

Another Stem Cell Proof Of Concept
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The technological demonstrations in stem cell medicine continue to roll in. Here, Genetic Engineering News reports on the latest from Advanced Cell Technology: "Therapeutic cloning, a technique aimed at producing stem cells for use in tissue replacement therapy to treat human degenerative diseases, will only be successful if the transplanted stem cells are able to survive and multiply over time, and evidence of such long-term survival has now been reported ... Many human diseases such as Parkinson's disease and spinal cord injury reflect loss of function of cells that are not repaired or replaced. This study demonstrates that it will be possible to use cloning to derive replacement cells that are immunologically matched to the patient."

Link: http://www.genengnews.com/news/bnitem.aspx?name=1001768XSL_NEWSML_TO_NEWSML_WEB.xml

Knee-Jerk Skepticism
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Michael Shermer, Scientific American's skeptic-in-residence, has run off a rather sub-par column on Kurzweil and healthy life extension. While I have to agree with him on points relating to supplements and Kurzweil (see some of my previous thoughts, harsh and more forgiving), Shermer makes a number of pronouncements with no basis in anything other than his own opinions. For example:

Two, I question the idea of extrapolating trend lines very far into the future. Human history is highly nonlinear and unpredictable. Plus, in my opinion, the problems of creating artificial intelligence and halting aging are orders of magnitude harder than anyone has anticipated. Machine intelligence of a human nature could be a century away, and immortality is at least a millennium away, if not unattainable altogether.

Personally, I think it's amusing to see someone think that developing general artificial intelligence is 10 times easier than defeating aging! I think that Shermer would benefit greatly from reading the work of Aubrey de Grey, who makes a very compelling case that we a) know more than enough to get going now on serious anti-aging research and b) making meaningful progress in radical life extension is only a matter of a few decades with the right level of funding.

In addition, I don't think that Shermer grasps the concept of escape velocity in healthy life extension. Even if true physical immortality is a thousand years away - a highly unrealistic thing to say in and of itself - all ("all") we have to do to live that long is to keep adding new medical technologies to extend healthy life span, bit by bit, more rapidly than one year ever year. This is not an unreasonable goal - it is within the capabilities of a large, directed research community. Kurzweil is quite clear about this concept in his writing, and presents it as developing a series of bridges to the future.

The sort of knee-jerk, unfounded skepticism of the sort expressed by Shermer - and millions of other people who think the same way - is one of the many obstacles to widespread support for healthy life extension research. The future is not a conveyor belt, but rather something that is built, brick by brick, by the actions of people. The future is directed, open to change, a road that could go in any direction. Just because something could be done does not mean it will be done: without public support and understanding of healthy life extension and its potential, research will not be funded and science will not move ahead. Skepticism becomes a self-fulfilling prophecy - which may briefly satisfy some folks, but we'll all be just as dead because of it.

Towards Cellular Programming
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A nice piece of news from Nature:

On 24 June, Kevin Eggan of the Harvard Stem Cell Institute told an international scientific meeting that his lab has fused a human embryonic stem cell to an adult skin cell. Eggan showed that the embryonic stem cell 'reprogrammed' the skin cell's nucleus, causing the skin cell to start behaving like a youthful, embryonic stem cell.

The fused cell can't be used for much - but it is a proof of principle for the future of tools that can change the state of cells. Our cells appear to be finite state machines on a level that scientists are beginning to be able to manipulate. Arrangements of genes and proteins determine how a cell behaves - whether it is a stem cell or a normal cell, for example. As biotechnology and medicine advances, scientists will be able to create stem cells - or any other type of cell required for regenerative therapies - as needed. This is a very worthwhile goal, the development of technologies to form a comprehensive biological repair kit capable of tackling a range of age-related disease and damage.

Progress Towards Curing Parkinson's
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Progress towards cures for the main categories of neurodegenerative disease is of great interest to healthy life extension advocates - other organs will be replaceable in years to come, but you certainly can't do that for the brain. All the damage has to be repaired in situ, and repaired well. This SciAm article gives a summary of recent progress in Parkinson's research: "Although much remains unknown about Parkinson's, the genetic and cellular insights that have come to light in just the past few years are highly encouraging. They give new hope for treatments that will combine with existing ones to slow disease progression and improve control of this distressing disorder."

Link: http://www.sciam.com/print_version.cfm?articleID=00078984-3758-12B3-A92783414B7F0000

SciAm: The Future Of Stem Cell Medicine
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A Scientific American special issue focuses on stems cells with a brace of articles and opinion pieces. Good stuff. "Stem cells serve as a biological repair system, with the potential to develop into many types of specialised cells in the body. They can theoretically divide without limit to replenish other cells. When a stem cell divides, each daughter can remain a stem cell or adopt a more specialised role such as a muscle, blood or brain cell ... Controlling this differentiation process is one of the biggest challenges in stem cell research. ... Biologists believe most degenerative diseases are too complex to treat effectively just by giving patients drugs or even gene therapy. Living cells, which produce a far larger number of biologically active molecules, stand a better chance of success."

Link: http://www.sciam.com/print_version.cfm?articleID=000BB369-6D99-12B8-AD9983414B7F0000

The Horrors of Aging
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There are no shortage of horrors in the world: famine, war, inhumanity and plague of a thousand stripes. It is human nature to hunch over and try to believe that it will never happen to us - those of us in the wealthy Western world might even be luckily correct in this belief. But degenerative aging - the result of accumulated, unrepaired damage to the complex machinery of our bodies - brings pain and suffering to best the most malignant disease. Do you think you know what lies ahead? Do you think you have come to terms with it? Read this harrowing account from See Spot CRON! ... read it all the way through. Those ugly details form the future that awaits everyone who is reading this now.

Without action now, your future will be one of pain and suffering, of the slow destruction of your body and mind. Aging is not noble. It is not romantic. It is a slow and increasingly terrible disease - no one goes quietly or with dignity.

But still, we do our best to put this out of our minds. Human nature at work. Yet there is hope - medical science is within decades of developing therapies to prevent and repair the root causes of age-related degeneration. However, the funding to make these therapies a reality will only be deployed in a climate of widespread support for rejuvenation and understanding of the possibilities. It is a matter of will and resources rather than a matter of science - the technological and medical path ahead is clear. The path of fundraising and awareness is not.

By refusing to face an unpleasant future, and thus failing to take the actions that could have saved us, we will doom ourselves to the very thing we feared to confront. We can do better. We can face the realities of aging and do something to make a difference - each and every one of us. The alternative is not pretty.

Stem Cell Technology Advances
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(From Medical News Today). One important portion of scientific research is developing the tools and techniques that will speed further work. The technologies for working with stem cells are improving, step by step: "Investigators from Memorial Sloan-Kettering Cancer Center (MSKCC) have used new techniques in the laboratory that allowed them for the first time to derive unlimited numbers of purified mesenchymal precursor cells from human embryonic stem cells. Mesenchymal precursor cells are capable of giving rise to fat, cartilage, bone, and skeletal muscle cells, and may potentially be used for regenerative stem cell therapy in bone, cartilage, or muscle replacement."

Link: http://www.eurekalert.org/pub_releases/2005-06/mscc-asf062305.php

Understanding Neurodegeneration
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Understanding of biochemical mechanisms enables faster research paths to targeted, effective therapies. Medical News Today notes progress in knowledge of mechanisms of a range of age-related neurodegenerative conditions: "Many of these diseases are characterised by accumulation, inside nerve cells, of clumps of toxic proteins. ... failure of the dynein system causes the degeneration in a form of motor neuron disease, and that it is also involved in other conditions such as Huntington's disease. [The study] also provided further evidence for the idea [that] a key factor in the severity of these diseases is the rate at which these toxic clumps of protein can be removed. Enhancing the degradation of these protein clumps has the potential to delay the onset of, or even reverse, this group of diseases."

Link: http://www.medicalnewstoday.com/medicalnews.php?newsid=26642

Late Conception, Genetics, Aging
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Randall Parker of FuturePundit comments on recent research into the genetics of women who can conceive at comparatively advanced ages. "One wonders whether the apoptosis genes were regulated to make cell death more or less likely in the late conceiving women. Did their ovary cells manage to avoid death and therefore hang around longer to reproduce? Or did their bad ovary cells more reliably die and thereby eliminate their harmful influence on neighboring cells? ... While women who have babies at late ages might have longer life expectancies there is a more obvious group to investigate for life extending genetic variations: really old people. A comparison of gene expression profiles between 90+ year olds and these late reproducing women might yield some insights into which gene expression profiles are most valuable for longevity."

Link: http://www.futurepundit.com/archives/002855.html

More Thoughts on Open Source / Garage Biotechnology
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A post from Frank at Anti-Aging Science & Medicine (commenting on some nice simulational biotech work at HHMI) made me think again about just how open source development methologies and cultures will shape the future of biotechnology.

What are the implications for garage biotechnology hacking? If bioinformatics was the sole technique, it would seem that anyone could have done this research in their garage with computer access to the genomics database and some know-how. My point is not to downplay the scientist's work but to present the possibilities for the amateur scientist in the light of "open source biotechnology".

Know-how is expensive, of course, but not as expensive as you might think. If the cost of entry is low (a low cost, high power computer, some general smarts, an investment of time) then someone with 1/10 of a high-level professional biotech know-how can produce useful results at 1/10 of the rate and effectiveness of the professionals. If they mess up, then they mess up - in simulation rather than with real genes in real organisms. Experimentation and diversity will be the order of the day when the only cost is the time of dedicated citizen scientists and the only downside is that some of that time will be wasted. Useful progress may be slow for each individual, but many, many people will be qualified to participate.

As I pointed out previously, this breaking down of the priesthood through lowered barriers to entry is how open source development has greatly advanced software development. It will do the same for biotechnology - hard problems requiring large investments in knowledge and resources will still typically be solved by scientific professionals working in traditional organizations, but they won't waste their time working on the easier issues. The much larger number of citizen scientists will be rapidly organizing to accomplish everything they are capable of and freely sharing the results of their work.

One benefit that truly stands out in this future is that research projects ignored by mainstream funding organizations stand a strong chance of making headway. One such presently ignored project is serious anti-aging research, work to find ways to prevent and reverse age-related damage - and soon. As biotech advances and computers become more capable, we activists are going to move from talking, educating and raising money to all that plus performing scientific research using the tools of open source biotechnology.

This is still some years ahead, however - the first generation tools, standards and platforms are still under evolving and under construction. See for example, to pick two quick, illustrative organizations at random, BIOS and the Open Bioinformatics Foundation. This process will accelerate the further it goes, and a large number of smart people are working on it. It's a bright future if the history of software development to date is anything to go by.

More Investment In Stem Cell Research
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The political climate seems to have calmed enough to encourage private investors to put money into developing stem cell therapies, as noted at Today's Stem Cell News. Patent filing statistics leads to the following conclusion: "The message from this report seems to be simple: biotech companies are undeterred by the hostile research environment that currently governs the stem cell sector. The market is aware that there is potentially a huge revenue stream from stem cell research - the world market value currently stands at $2.7 billion and is set to grow significantly over the next few years." If you want something done, let people get on and do it - enough with the threats of legislation and regulation already.

Link: http://www.stemnews.com/archives/000957.html

Dangerous "Anti-Aging" Nonsense
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The less reputable end of the "anti-aging" marketplace - which includes Revlon and other large makers of useless cremes and potions - is mostly concerned with peddling junk that is only going to harm your wallet. However, dangerous procedures and services surface at the intersection of the "anti-aging" marketplace and the practice of medicine. In particular, the present hype over stem cells is leading to some very unethical, unsafe, overhyped procedures from those who consider the desperate and credible to be cash cows. Medicine is as finance - if someone is promising amazing returns on investment, then they're either stupid or a crook. Either way, it's buyer beware: do your research, make smart decisions and be a late adopter.

Link: http://www.cnsnews.com/news/viewstory.asp?Page=%5CForeignBureaus%5Carchive%5C200506%5CFOR20050624a.html

Stress And Aging
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From FortWayne.com, an article that examines the relationship between the physiological effects of stress and the rate of aging. Like inflammation, stress causes changes that can be considered as "running the engine hot" or as a form of cellular damage. As the Reliability Theory of aging tells us, either of those things are likely to reduce our life span and make us less healthy as time goes on. You should skip over the flawed discussion of an upper limit to life span, however - Reliability Theory suggests that there is no such thing (aging is a consequence of accumulated damage), and even if aspects of aging turn out to be programmed into to your genes then future biotechnology will be developed to do something about that programming.

Link: http://www.fortwayne.com/mld/journalgazette/living/11985302.htm

Mprize For Rejuvenation Research Continues to Grow
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If you haven't dropped by the Mprize website recently, you sould certainly do so.

The Methuselah Mouse Prize is the premiere effort of The Methuselah Foundation; a scientific competition designed to draw attention to the ability of new technologies to slow and even reverse the damage of the aging process, preserving health and wisdom in a world that sorely needs it.

The pledge total for the Rejuvenation and Longevity research prize fund has passed $1.3 million, and more than 50 people are now members of The Three Hundred organization. The number of endorsing organizations continues to grow and the news articles roll in. In short, things are moving forward; good progress is being made thanks to the many generous donors and volunteers who have stepped forward to date. Reinforce success in advocacy for the fight to cure aging and make your pledge today!

InfoAging on Mitochondria
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While wandering the wilds of the world wide web, I noticed that InfoAging (a very useful online project funded by the American Federation for Aging Research) updated their section on mitochondria and age-related degeneration just a few months ago.

Mitochondria are the cells' energy converters. We need them to transform nutrients into the energy we need to live. Mitochondria also produce damaging oxidant - free radical molecules produced by the metabolism of oxygen - that can wreak havoc on cells and their DNA. As the source of these toxic products, mitochondria are also their first potential victims. Their proximity to the free radicals they produce, combined with their exceedingly intricate structure, make them particularly vulnerable to injury over time. Not surprisingly, researchers are seeking to understand this injury as a critical part of the aging process, and perhaps a cause of a host of age-related diseases.

Since InfoAging is an excellent resource for the layman who wants to know about current aging research and the conservative scientific consensus on aging, and since I've been talking about mitochondrial research of late, I thought I would point this out.

A Larger Stem Cell Conference
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(From SFGate). The health of a field can be measured by the size of its conferences - and judging by the latest yearly conference of the International Society of Stem Cell Research, things are going well for the still-young field of stem cell medicine. "The record turnout represents a 50 percent increase from a similar conference last year ... The very fact that 2,100 people are here says a lot. As far as we know, it's the most in history for the stem cell field." Scientists are trying to use these events to dampen media hype to sensible levels - "managing expectations" as it's known in business. A representative comment: "I am not pessimistic about the future, but I think this will take a very long time."

Link: http://www.sfgate.com/cgi-bin/article.cgi?f=/c/a/2005/06/24/BAGV9DE8I41.DTL

Cultivating Adult Stem Cells
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The field of stem cell research, while very promising, is still in its first stages - akin to gene therapy a decade ago. The cultivation of stem cells in the lab is still in the process of exploration and standardization even as researchers are pushing forward with trials for first generation therapies. Here, the Post-Gazette reports on a new step forward in the basics: "Stem cells obtained from adult muscle can multiply as often as stem cells from embryos, indicating that adult-derived cells could be cultivated for treatment purposes. ... Cells that had doubled 200 times seemed as 'fresh,' in Huard's words, as those from 50 doublings. They still carried the markers of stem cells and were able to repair muscle fibers in transplanted mice."

Link: http://www.post-gazette.com/pg/05175/527726.stm

How Much Would You Pay To Live Forever?
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No, really, how much would you pay to live forever?

Think of it this way: What is your willingness to pay to live forever? I'd happily pay all my earnings in excess of $10,000 in perpetuity - a present value of millions of dollars.

OK, but what is your willingness to pay for a bottle of medicine that a spammer says will let you live forever? I wouldn't pay a penny.

Are doctors no more credible than spammers? That's going too far. But the bottom line is that life is precious, but at least on average, medicine is not.

Those interested in healthy life extension should also be interested in the economics of medicine, research and life itself. Attaining an understanding of the basics and the subtleties is well worth it (and a good start would be to add the Ludwig von Mises Institute daily articles and blog to your reading list). Understanding the whys and hows of cost - in the wider sense of the word - is key to understanding how a society of individuals works (or doesn't work) in order to advance medical technology. Thus it is also key to understanding what efforts are likely to help the development of working longevity medicine after the SENS model. Economic thinking is a good thing: embrace it.

A Clever Application
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Medical News Today reports on a clever application of new knowledge and capabilities related to controlling cells: "We used the brain's own signaling molecules to guide the genetically modified monocytes along a concentration gradient to the degenerating brain cells ... We showed that improvement of the disease was directly related to the amount of genetically modified monocytes reaching the degenerating brain cells. The improvement was clearly linked to the ability of the corrected neurons to break down excess GM1 with the enzyme delivered by the monocytes." While this was not aimed at an age-related neurodegenerative disease, we can expect to see many more similarly clever therapies as the knowledge base grows.

Link: http://www.medicalnewstoday.com/medicalnews.php?newsid=26473

Gene Expression And Aging
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An article from Genomics & Proteomics takes a broad look at changes in gene expression with aging - and hints of ways in which to intervene in the process. Interestingly, there is mention of developing biomarkers for physiological age: "We just now have molecular markers for aging in the kidney. If I did the same thing, we could have molecular markers for aging in the muscle, liver, or skin. These markers don't tell how many years you've lived; they tell your relative health. You could turn these into terrific clinical markers, and you would know whether someone is 40 and looks like they're on a bad trajectory, or if they're 80 and you could treat them as a 40-year-old." The current absence of meaningful biomarkers makes it difficult to usefully discuss the results of therapies.

Link: http://www.genpromag.com/ShowPR~PUBCODE~018~ACCT~1800000100~ISSUE~0506~RELTYPE~GPF~PRODCODE~00000000~PRODLETT~W.html

An Interview With James Thompson
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You folks may find this of interest: a long MSNBC interview with biologist James Thompson on topics relating to stem cell research. Some of the more interesting items:

Q: How do you respond to the claim that we have these other sources of stem cells - adult stem cells or cord blood - and there's no need to turn to embryonic cells?

A: We don't. The most studied cell in the whole body, in terms of stem cells, is the hematopoietic stem cell. It can't be grown. So what you do when you do a bone marrow transplant is you take some bone marrow out of you - actually, we do peripheral blood - and we put in another patient without expanding it. There's a clinical need for that expansion step, but it can't be done right now. And hundreds of labs for 30 years have studied that adult stem cell, and that's the one we know the most about.

...

And again, getting back to the basic science thing: If we study the embryonic stem cells, we learn the basic science. That knowledge is just as likely to be applied to adult stem cells as to the embryonic stem cells. The knowledge goes back and forth. And in the case of the blood, people have failed at growing that cell for three decades. Well, studying that lineage with embryonic stem cells, we might learn the clues to make it growable, and it might be that we still want to use adult stem cells to do that because there are a lot of advantages to that, but the knowledge might come from embryonic stem cells.

Stem cell research really all boils down to a matter of trying to fully understanding and controlling our cells. If researchers can learn to do that, then opportunities to develop cures for aspects of degenerative aging simply fall out of the process.

Q: What are some of those guesses about other technologies?

A: Well, if you take a nucleus and you put it into an oocyte [egg cell], the oocyte knows how to reprogram things. That's a problem that we can study, to understand how that happens. We don't really have a lot of information about how that works, so it's hard to predict how long it's going to take to solve that problem. I'd be surprised if within 10 years we didn't have another way to solve the problem, but it could be that it's a very, very hard problem and it's going to take a long time to do it.

Q: To find a way for a normal cell to reprogram itself?

A: Right. The message of Dolly is less about cloning, that we can clone Dolly or we can clone people or even do nuclear transfer to make embryonic stem cells; it's that the differentiated state is in principle reversible. And while that was known for a lot of model organisms, and there was even some evidence for that in mammals, Dolly really drove the message home that it was simply a question of time before we understood how to do that.

There's much more; it's well worth reading.

Finding New Stem Cell Sources
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Over the past year, researchers have been finding more new sources of potentially useful adult stem cells. Here, a Newswise press release details some of the latest research: "Researchers at Wake Forest University School of Medicine have successfully isolated stem cells from human skin, expanded them in the laboratory and coaxed them into becoming fat, muscle and bone cells. The study [is] one of the first studies to show the ability of a single adult stem cell to become multiple tissue types ... The research team grew mesenchymal stem cells, a type of stem cell normally found in bone marrow. ... Compared to bone marrow, a skin biopsy is easy to take, so it offers advantages for clinical use. The cells can be obtained from any small sample of human skin."

Link: http://www.newswise.com/articles/view/512694/

EMBO Reports Interviews Aubrey De Grey
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A pleasant midweek piece from EMBO Reports: a focused, sensible interview with biomedical gerontologist Aubrey de Grey. "There is a consensus within society that ageing is not a disease and therefore not an appropriate target for the biomedical approach. That's the problem. ... We define ageing as undesirable, that is what it comes down to. I consider myself a biomedical gerontologist - someone who is interested in developing technologies that do something about ageing. I distinguish myself from biogerontologists, who are mainly interested in understanding ageing but not necessarily in doing anything about it ... The reason that voters think curing ageing is a pipe dream is because television only shows my colleagues talking about what they can get funded."

Link: http://www.nature.com/embor/journal/v6/n3/full/7400354.html

Keeping Up With the Times
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A change in focus is announced over at Betterhumans, historically a good source of healthy life extension news:

Today, for the first time, users of Betterhumans.com can submit news directly for approval by an editor. It wasn't easy to make this decision, but for several reasons I think that it's for the best. And it reflects a significant change in my thinking about the site.

Betterhumans is doing a good job of straddling the line between old style and new style online media; they're effectively the online face of moderate transhumanism, a news and opinions venture with quite a respectable readership. But the reality of online publishing, as Simon points out, is that it's a place for those who love to do it - not for those who want to make money.

The healthy life extension community has a strong voice; many good writers are blogging and speaking out because they want to, not because they're chasing dollars. If Betterhumans can provide a silver-edge frame (and tens of thousands of page views) for the many folks who can write a silver-edged article (worthy of tens of thousands of page views), then more power to all involved.

So if you blog or write on the topic of healthy life extension, consider making a submission to Betterhumans every now and again. After all, the very worst that could happen is that ten thousand people will have a chance to listen to your point of view and critique your ideas.

More On Aging And Stem Cells
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A short piece from Forbes is illustrative of what scientists are thinking about stem cells and aging these days: "In older mice, bone marrow stem cells that create new blood cells produce fewer immune cells. That means the bodies of older mice are less able to fight infection. As well as producing fewer immune cells, the aging blood-forming stem cells use genes known to be involved in leukemia - cancers that affect blood cells. This may be one reason why older people have an increased risk of developing certain kinds of leukemia ... Aging results in a diminished capacity of the body to maintain tissue and organ function. Since we know the cells mediating this maintenance are stem cells, it doesn't take a great leap of faith to think that stem cells are at the heart of that failure."

Link: http://www.forbes.com/lifestyle/health/feeds/hscout/2005/06/21/hscout526401.html

The Methodical March
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SAGE Crossroads outlines the "Methodical March to Immortality," a good summary of the polar opposite of SENS in gerontology. Where Aubrey de Grey makes a good case that we know more than enough to begin the war on aging now, the methodical march crew want to move slowly, completely, genome by genome, five year project by five year project. The first, "funded by the Ellison Medical Foundation, [will] begin by scouring the entire yeast genome for genes that regulate longevity. The researchers will then take these life-extending genes and search for their counterparts in worms and mice." There is a time and place for completeness in science, but it isn't fast - and we need rapid development if we are to avoid the age-related disease, degeneration and suffering that has befallen every human to date.

Link: http://www.sagecrossroads.net/Default.aspx?TabID=28&newsType=ArticleView&articleId=120

Alzheimer's Predictor Developed
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Randall Parker of FuturePundit reports on new research into predicting Alzheimer's: "Researchers have developed a brain scan-based computer program that quickly and accurately measures metabolic activity in a key region of the brain affected in the early stages of Alzheimer's disease. Applying the program, they demonstrated that reductions in brain metabolism in healthy individuals were associated with the later development of the memory robbing disease." As he notes, "the greater value of this finding is in research on methods to prevent or delay the onset of Alzheimer's Disease." The next step is to understand the biochemical mechanisms of early Alzheimer's development that make this predictor possible.

Link: http://www.futurepundit.com/archives/002842.html

Inflammation Isn't Good Either
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Chronic inflammation has been identified as a risk factor for numerous age-related diseases and shorter, less healthy lives. In effect, inflammation acts as a source of damage to the complex biological machines that are our bodies - one reason why the defeat of common chronic disease has lengthened life spans. This item from EurekAlert links yet another age-related condition to inflammation: "A new study of dementia in identical twins suggests that exposure to inflammation early in life quadruples one's risk of developing Alzheimer's disease. ... The surveys included questions about loose or missing teeth. Gatz and colleagues used the answers to build a crude indicator of periodontal disease. ... The conclusion is not that good oral health can prevent Alzheimer's, but that an inflammatory burden early in life, as represented by chronic gum disease, may have severe consequences later."

Link: http://www.eurekalert.org/pub_releases/2005-06/uosc-adl061605.php

More on the A4M - Olshansky Lawsuit
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I'll start by saying that I've talked on this topic before, so you should probably head back into the archives to get the background. (I should probably note that I'm far less down on S. Jay Olshansky than I was in October of last year, but my thoughts on A4M are much the same now as then). You can see a summary of the latest press at The Raw Story:

The defamation case is an almost unheard-of attempt to punish academics for comments made in their professional capacity, said experts on libel law and academic freedom. Although UIC is not a defendant in the suit, officials there said they are so concerned about protecting scholarly speech that the school is picking up Olshansky's legal bills.

...

The plaintiffs, osteopathic physicians Ronald Klatz and Robert Goldman, say the 1st Amendment's free speech protections do not cover the actions of Olshansky and co-defendant Dr. Thomas Perls of Boston University. Klatz and Goldman blame the defendants' criticism for a series of recent professional setbacks, including cancellation of an anti-aging conference to have been held this month in Singapore, and termination of a contract to develop anti-aging products that could have been worth $20 million.

I will say that I think it's quite right to be calling out A4M if we feel - as many do - that they are doing just what they accuse obvious frauds in the "anti-aging" marketplace of doing: putting money before ethics and scientific backing, or promoting dubious claims. A4M is a business, and a business with the potential to do a great deal of good for the healthy life extension cause. If they are not living up to that potential, then we as consumers need to stand up and make sure we are being heard - getting businesses to act responsibly is a great deal easier than getting politicians to do the same, after all:

Even those for-profits that cater largely to other businesses - such as A4M - are a great deal more responsive to public opinion (as expressed in dollars and page views) than anything else you might find out there. You can pass on your opinion loud and clear by being an educated, aware, vocal customer. Vote with your wallet; don't buy products branded as "anti-aging." Write outraged letters to businesses that are clearly jumping on the "anti-aging" bandwagon and insulting your intelligence. Support medical research and organizations that take a responsible attitude towards longevity and aging research. Talk loudly about your choices as a consumer and why you are making them - ultimately, those business ventures that succeed determine the look of an entire market. We - people like you and I - decide which business ventures succeed via our choice of where to spend our time and money.
Obesity Is Bad, Part XIV
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Newsweek cuts right to the chase in this article on obesity and health: "Whatever the exact relationship between obesity and mortality, there is no question that excess weight can ruin your health. Obesity can foster diseases ranging from cancer to heart failure, and it's a clear factor in the country's growing epidemic of type 2 diabetes. ... So don't place too much stock in the latest mortality figures. If you value your legs and your eyesight, warding off type 2 diabetes should still be a priority. ... Diabetes is the quintessential lifestyle disease. But lifestyle diseases have lifestyle cures, and the only side effects are good ones." If you don't want to suffer crippling - and ultimately fatal - age-related diseases as a result of excess weight, the solution is fairly clear.

Link: http://msnbc.msn.com/id/8270739/site/newsweek/

More Engineered Blood Vessel Progress
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(From Newswise). In an important step forward for tissue engineering, scientists have grown muscle mass complete with an embedded blood vessel system and implanted it in a mouse. "Until now, most scientists have not attempted to provide engineered tissue with its own blood supply. Instead, they have implanted the new tissue into the body and waited for the body itself to infiltrate the tissue with blood vessels. ... The different cells quickly organized themselves on the scaffold, with the myoblast cells transforming into aligned and elongated muscle fiber tubes and the endothelial cells organizing themselves in tubes nestled between the myoblasts." Clever stuff - getting the blood vessels right has been a stumbling point for growing larger tissue masses.

Link: http://www.newswise.com/articles/view/512602/

Frontiers of Aging
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Aubrey de Grey pointed me to an Australian ABC Radio National show on religion and radical life extension. Here is the summary:

Living longer fascinates us today as much as it ever did. The modern elixirs of life are the special foods and fad diets while the cosmetics industry profits more than ever from our desire to look young. Scientists too, are in on the act as they always have been, though now they have a new weapon - genetic engineering - which promises to be able to cure and prevent the processes in our cells that lead to ageing and death - and to increase our life-spans dramatically. Like magic and alchemy before it, modern science may be on the verge of solving the long quest for immortality. But what if it's our mortality that makes us human? Encounter this week explores the frontiers of ageing.

The RealPlayer audio file can be downloaded here. I'm sure we all know where I stand on the "mortality that makes us human" point - so far as I'm concerned all that mortality makes us is dead. It's hard to be human, or much of anything for that matter, when you're dead. I have nothing against people who want to age and die, but please respect our right to engineer longer, healthier lives for those who want them!

Stem Cell Research Funding Emerges
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Private funding for stem cell research is starting to pick up now that the political climate is merely unsettled (an improvement from dire and threatening). From Medical News Today we hear that Columbia University Medical Center is "halfway toward realizing the first phase of a multi-year campaign ... the $50 million goal for the first stage of the campaign, $25 million has been raised from the private sector, specifically for diabetes and neural stem cell research. ... The initial $50 million for the Columbia Stem Cell Initiative will enable Columbia to outfit a new stem cell center, construct a state-of-the-art facility to produce cells for experimental and therapeutic use, and establish a separate laboratory dedicated to growing new human embryonic stem cells for new studies."

Link: http://www.medicalnewstoday.com/medicalnews.php?newsid=26217

Immortality Institute Conference
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Betterhumans reminds us that the Immortality Institute Conference takes place in November in Atlanta, Georgia - and offers a discount on conference registration to Betterhumans premium members. Bruce Klein of the Institute has a simply amazing network of connections in the transhumanist and healthy life extension communities - this is reflected in the list of speakers, which includes Aubrey de Grey and Ralph Merkle. For good measure, "a screening of of the Immortality Institute's documentary film Exploring Life Extension will also take place during the conference." If you haven't yet experienced the Immortality Institute forum - an energetic place if ever there was one - now would be the time to dive in.

Link: http://www.betterhumans.com/Events/Event/tabid/87/Event/160/Default.aspx

Reporting on Aubrey de Grey at Stanford
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Mike Linksvayer reports on the recent presentations given by Aubrey de Grey at Stanford University:

The second talk, apparently more intended for biologists, was a repeat of the first to a disappointing extent. I was prepared to understand very little, but de Grey only spoke for awhile on one of his proposed solutions to one of the seven types of damage - extracellular junk. The solution takes a cue from bioremediation: find microbes that break down the extracellular junk. Where? Human remains of course. From Appropriating microbial catabolism: a proposal to treat and prevent neurodegeneration:

"Soil microbes display astonishing catabolic diversity, something exploited for decades in the bioremediation industry. Environments enriched in human remains impose selective pressure on the microbial population to evolve the ability to degrade any recalcitrant, energy-rich human material. Thus, microbes may exist that can degrade these lysosomal toxins. If so, it should be possible to isolate the genes responsible and modify them for therapeutic activity in the mammalian lysosome."

Neat idea. Later de Grey said that this idea is the easiest to explain to non-specialists and that the others that he has personally worked on would have required far longer to introduce than the hour lecture format allowed.

de Grey is attempting to jump start anti-aging interventions with the Methuselah Mouse Prize[s] for extending the lifespan of mice, inspired by the X Prize. His "engineering" approach sounds good to me and I wholly endorse the goal of defeating aging. I will donate more once more information is provided about the participating scientists and their mice - not much is available at this point.

I'll take that as a sign that we volunteers need to put more effort into obtaining information from the Mprize competitors and potential competitors - as anyone who works in science knows, getting usefully formatted information out of busy scientists is hard work in and of itself. However, donors who are invested in the march towards healthy life extension technologies (which would be all of them, I hope) need to see progress in order to validate their donations - I know I feel that way about the use of my money. So, more effort needed!

More on Open Source Biotechnology
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After my recent posts on the future of open source biotechnology, I received an email from Ray Van De Walker to provide a contrary viewpoint:

Briefly, my credentials:

I have seven years of experience developing biomedical software. Several products have achieved FDA and CE approvals, and are in mass-produced use by patients.

Here's the problems:

1. The market itself does not tolerate design defects. The established standard is less than one unanticipated risk per billion patient hours, and the evidence trail has to hold up in court or sellers will be successfully sued by patients for whom the therapy failed.

2. In the U.S., to advertise or sell a therapy, the FDA requires evidence of safety and effectiveness. The European union just requires evidence of safety; effectiveness is left to doctors and patients.

a) Therefore the therapy has to have traceable continuity in testing or safety engineering, including maintenance of test results at an agency or person that can be held liable by the FDA or (in the case of the EU) a government's regulatory agency. Most organizations and sane people will not accept liability without an income stream to pay for the liability insurance, which of course is extremely expensive for medical therapies.

b) To meet effectiveness requirements in the U.S. there must be patient trials to prove the therapy. The patient trials are extremely expensive, because the doctors, hospital time, etc. are expensive (Most do not work pro-bono). I.e. close to quarter billion dollars for a major drug using a new metabolic pathway to be certified. Medical devices (much cheaper) only cost 25 to a 100 million if the therapy they perform is not experimental.

Contrast that with open-source software, which basically says that if there's a defect, then it's up to the user to fix it or live with it.

Production would not be a problem, I think. The market selling open source therapies could be much like that for generic drugs. The producers would have to have certified quality organizations, but generic producers already do that.

For my part, I have to say that agree with these two central points:

  • Centralized regulation kills open source approaches to development for exactly the same reasons it damages the market - imagine the consequences of centralized regulation of server software. We'd still be paying $50,000 for 200MHz machines and hand-testing factory RAM for errors.

  • Many medical applications require a level of reliability that traditional-model open source groups do not approach. The same is true of many software applications.

I do think that we can fairly quickly point to a large swathe of medicine and medical science that could benefit from improvements in lower-reliability methodologies. The practice of neurosurgery will probably not be a part of this swathe - but I'm willing to bet that most in vitro and simulational medical research certainly will be.

A larger range of medicine would also benefit from lower-reliability methods in the absence of centralized, monolithic, risk-averse regulation - say, with distributed, competitive, accountable review instead, allowing individuals to adopt risk levels as they feel appropriate, just as in all other walks of life. Most applications of medicine and most basic medical research does not need the fault tolerance expected of air traffic control or rocketry systems ... or neurosurgery for that matter.

Relationships Between Cancer And Aging
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A report from the LEF News concisely notes the ways in which cancer and aging are thought to be related: "Adult stem cells are responsible for tissue renewal and exhaustion of their replicative capacity may contribute to tissue aging. Loss of unlimited proliferative capacity in some of the adult stem cells and/or their progenitors may have involved the evolutionary trade-off: senescence prevents cancer but may promote aging. Embryonic stem cells exhibit unlimited self-renewal capacity due to the expression of telomerase. Although they possess some cancer cell characteristics, embryonic stem cells exhibit a remarkable resistance to genomic instability and malignant transformation. Understanding the tumor suppressive mechanisms employed by embryonic stem cells may contribute to the development of novel cancer treatments and safe cell-based therapies for age-related diseases."

Link: http://www.lef.org/news/LefDailyNews.htm?NewsID=2339&Section=AGING

Progress In Growing Blood Vessels
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(From MSNBC). Growing blood vessels is something of a sticking point in the tissue engineering of organs or even modestly sized masses of tissue - so it is good to hear that progress is continuing in this area. "Scientist have grown human blood vessels from cells taken from elderly patients in a ground-breaking experiment that could lead to new treatments for heart disease within the next decade.
... Growing new blood vessels from a patient's own cells would enable doctors to bypass clogged arteries in patients whose own vessels are not suitable. ... The scientists, who reported their research in The Lancet medical journal, grew blood vessels in the laboratory from cells taken from four men aged 47-74 who were having coronary bypass surgery."

Link: http://www.msnbc.msn.com/id/8243078/

Rafal Smigrodzki's Research into Mitochondria
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Researcher Rafal Smigrodski was kind enough to post a preview of a forthcoming Rejuvenation Research paper to the ExI Chat List today:

A few months ago I promised to post an article on mitochondria and aging which I was writing with Shaharyar Khan, and finally I can keep my promise. "Mitochondrial microheteroplasmy and a theory of aging and age-related disease" will be published in Rejuvenation Research in August. Here is the text (without figures) and I can send the pdf to anyone interested.

...

We implicate a recently described form of mitochondrial mutation, mitochondrial microheteroplasmy, as a candidate for the principal component of aging. Microheteroplasmy is the presence of hundreds of independent mutations in one organism, with each mutation usually found in 1 - 2% of all mitochondrial genomes. Despite the low abundance of single mutations, the vast majority of mitochondrial genomes in all adults are mutated. This mutational burden includes inherited mutations, de novo germline mutations, as well as somatic mutations acquired either during early embryonic development or later in adult life. We postulate that microheteroplasmy is sufficient to explain the pathomechanism of several age-associated diseases, especially in conditions with known mitochondrial involvement, such as diabetes (DM), cardiovascular disease, Parkinson's disease (PD), and Alzheimer's disease (AD) and cancer. The genetic properties of microheteroplasmy reconcile the results of disease models (cybrids, hypermutable PolG variants and mitochondrial toxins), with the relatively low levels of maternal inheritance in the aforementioned diseases, and provide an explanation of their delayed, progressive course.

As long-time readers will be aware, Rafal has an enviable position with a research group focusing on mitochondria, working on important projects such as tools to manipulate and repair mitochondrial damage. While there is still a great deal of uncertainty in the relationship between mitochondria and aging (all the more reason for more funding), it is quite clear that this is a very promising avenue of research for healthy life extension. As I'm sure you know, repair of mitochondrial mutations is one of the seven pillars of Aubrey de Grey's Strategies for Engineered Negligible Senescence (SENS).

Hibernation And The Thymus
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An intriguing article from Betterhumans looks at research into hiberation and its connection to regeneration. "The thymus is a tiny organ located near our breastbone that is present in all mammals. It is the major site for T lymphocyte differentiation and immune response. In humans, the thymus is most active during puberty, but as we age it shrinks and loses functionality, leading to immune system decline and increased susceptibility to colds, flu and other ailments. But the thymus doesn't degenerate in all mammals. Hibernating animals such as the Alaskan ground squirrel are able to renew the lymphoid tissue of their thymus as they sleep every winter." Highly speculative research is often the most interesting - and regeneration of the aging immune system is an important goal.

Link: http://www.betterhumans.com/News/News/tabid/61/News/776/Default.aspx

Towards A Parkinson's Vaccine
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Nature reports on progress towards a vaccine for Parkinson's disease - but it's early days yet. "A vaccine developed to fight brain disorders such as Parkinson's disease has shown promise in preliminary animal trials. But experts caution that the positive results may not translate into an effective treatment for humans. The formation of abnormal protein aggregates in the brain, known as Lewy bodies, has been linked to several neurological disorders in adults. ... Many think that getting the immune system to attack the protein aggregates is a good step towards finding a treatment. So several research teams have been pursuing therapeutic vaccines. Biologists have already succeeded in giving mice specially designed immune cells to save them from neurological damage. Now they have gone a step further by getting mice to produce their own immune protection through a series of injections."

Link: http://www.nature.com/news/2005/050613/full/050613-5.html

What Is Aging?
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The Washington Times ponders the nature of aging: "What you mean by aging, and the genetics of aging, varies with different people. It's an unsettled question at present. There are many theories of aging, and they are all persuasive. In all cases, there is an environmental component, but the response has a genetic component. At one extreme, [aging] can be defined as the composite of a lot of pathological problems -- some people develop kidney troubles [as they age], etc. The other view is that there is an independent process of aging quite apart from pathology. Depending on the type of definition, you have a lot of different factors involved. Aging becomes like pornography. You know it when you see it."

Link: http://www.washingtontimes.com/functions/print.php?StoryID=20050613-093849-4799r

More Medical Nanomachines
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Randall Parker of FuturePundit has more on new research aimed at developing medical nanomachines - to deal with arterial plaque in this case. He makes a good point: "This is another example of development of a treatment that falls within the typology of 7 Strategies for Engineered Negligible Senescence (SENS) to halting and rejuvenate bodies by the removal of accumulated extracellular junk. ... Widespread acceptance of SENS for rejuvenation is not necessary for the development of many SENS treatments. My guess is that for at least the next decade most treatments which will accomplish objectives which support SENS will be justified under the old paradigm of development of treatments against specific diseases. Efforts such as this one develop tools that will be useful for rejuvenation. So we are making progress toward the goal of engineered negligible senescence or perpetual youth."

Link: http://www.futurepundit.com/archives/002832.html

Revisiting the Culture of Entitlement
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Thoughts on the culture of entitlement are noted by Glenn Reynolds:

Americans now feel entitled to spend nearly a third of their adult lives in retirement. Their jobs are less physically demanding than their parents' were, but they're retiring younger and typically start collecting Social Security by age 62. Most could keep working - fewer than 10 percent of people 65 to 75 are in poor health - but, like Bartleby the Scrivener, they prefer not to.

I've discussed this issue in the past and noted that the real problem is not that people feel entitled, but that our vast, crooked, centralized government can be manipulated to enable those who feel entitled to steal resources from the rest of us.

A culture of entitlement is damaging for everyone, at every age: we are all, ultimately, responsible for our own lives, health, wealth and happiness. If ever-larger capable, healthy, active portions of the populace continue to engineer our society to obtain resources for themselves at the expense of others, the system will collapse.

This all ties back into the giant Ponzi scheme that is social security - essentially a way for people who are, on average, wealthier to vote themselves resources from people who are not. The problem is not that people are going to be people, but that centralized, massive government enables the worse aspects of human nature to cause so much economic harm.

A related area of entitlement - accompanied by political debate, puffery and grave misunderstandings over the way the world actually works - is medical provision and insurance. Ronald Bailey takes a look and nails the real costs:

Which suggests the following thought experiment - what if the United States had nationalized its health care system in 1960? That would be the moral equivalent of freezing (or at least drastically slowing) medical innovation at 1960 levels. The private sector and governments would not now be spending so much more money on health care. There might well have been no organ transplants, no MRIs, no laparoscopic surgery, no cholesterol lowering drugs, hepatitis C vaccine, no in vitro fertilization, no HIV treatments and so forth. Even Canadians and Britons would not be satisfied with receiving the same quality of medical care that they got 45 years ago.

Everybody pays more to obtain improved pharmaceuticals, imaging technologies, cancer therapies, and surgical techniques. The happy result is that average life expectancy has increased by about eight years since 1960.

The encroachment of socialism in medicine in the US should be of grave concern to those interested in longer, healthier lives and a future of better medical technology. Without a dynamic free market, the pace of medical progress grinds to a halt - regulation could literally cost us our lives. As Bill Walker noted:

If telomerase inhibitors were a new kind of computer chip, they would have been on every Wal-Mart pharmacy shelf and selling for ten dollars a bottle by now.

And there would be twenty competing review organizations providing responsible, comprehensive risk-evaluations for another few dollars. This sentiment is true of every aspect of medical research, every new potential therapy that could help with age-related disease or aging itself. The present system of centralized review gives us the worse of all worlds - it greatly slows research while still being largely ineffective at its stated goals.

Folding@Home Team Update
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The growing Longevity Meme Folding@Home team has been doing well over the past few weeks, powering past the 700 mark in the team listings. A warm welcome to the new folders and congratulations to all taking part - keep up the good work.

I'll set a goal now: when we hit 500, I'll be handing out commemorative team goodies for all the members. If you have opinions on the type of handouts and the logos they should bear, just post your thoughts below. If you're not already signed up for Folding@Home, then now would be the time to get involved! Make use of all that spare processor time currently going to waste on your home machine and help to advance the cause of medical science.

Regenerating Brain Cells
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Progress towards complete understanding and control of our cells continues, step by step. The Independent reports on the latest new research: "Scientists have grown fully mature brain cells in a laboratory for the first time, using a technique that mimics the natural process of brain regeneration. It promises to open the door to new ways of treating and possibly curing debilitating brain diseases such as Parkinson's, epilepsy and Alzheimer's. ... Now we can make a lot of brain cells from just a very small number of these stem cells, which is great because we'd have to do that to repair neurological disease. ... The home run is that we will find drugs to mobilise our own population [of brain stem cells]."

Link: http://news.independent.co.uk/world/science_technology/story.jsp?story=646759

Still Smoking? Not Good At All...
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There are many, many good reasons to quit smoking already - but Nature provides a new and very compelling one: "Like the plastic tips on the ends of shoelaces, telomeres help to protect genes against wear and tear. ... Tim Spector [and] his team have shown that telomeres shrink dramatically in patients who are obese or heavy smokers. ... Heavy smokers, who consumed a pack a day for 40 years, showed seven years of extra biological ageing. Researchers already knew that smoking and obesity could cause a kind of stress in cells that produces reactive chemicals, which in turn are known to wear away telomeres. Spector's large study looks directly at this effect to quantify just how much a cigarette can age you."

Link: http://www.nature.com/news/2005/050613/full/050613-3.html

Nanotechnology And Stem Cells
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From the Washington Times, some topical nanotechnology boosterism: "Cutting-edge nanotechnology is beginning to help advance the equally pioneering field of stem-cell research, with devices that can precisely control stem cells and provide self-assembling biodegradable scaffolds and magnetic tracking systems ... Nanotechnology might show people once and for all that you really can help regenerate organs with stem-cell biology and help people walk again, help people after heart attacks, help people after stroke." This is early nanotechnology - nanoscale manufacturing turned to medical applications rather than true nanorobots or other more futuristic plans.

Link: http://www.washtimes.com/upi-breaking/20050610-125435-4252r.htm

Aging And Mitochondrial Dysfunction
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More attention is going towards the relationship between degenerative aging and mitochondrial dysfunction - given that this is one of the seven pillars of Aubrey de Grey's SENS, I think that this is a good thing. From the Life Extension Foundation News, a brief note on recent research: "Cumulative [mitochondrial DNA (mtDNA)] damage occurs in aging animals, and mtDNA mutations are reported to accelerate aging in mice. We determined whether aging results in increased DNA oxidative damage and reduced mtDNA abundance and mitochondrial function in skeletal muscle of human subjects ... These results demonstrate that age-related muscle mitochondrial dysfunction is related to reduced mtDNA and muscle functional changes that are common in the elderly."

Link: http://www.lef.org/news/LefDailyNews.htm?NewsID=2315&Section=AGING

The Molecular Basis of Lifespan Becomes Clearer
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It's always good to see the basic concepts of healthy life extension permeating throughout the scientific community - and being expressed more forcefully, since scientists tend to be conservative for reasons relating to funding and common human nature. So I am pleased to see this abstract from the Journal of Hypertension:

Objective: Although the quest for longevity is as old as civilization itself, only recently have technical and conceptual advances in genomics research brought us to the point of understanding the precise molecular events that make us age. This heralds an era when manipulations of these will enable us to live longer, healthier lives. The present review describes how recent experimental strategies have identified key genes and intracellular pathways that are responsible for ageing and longevity.

Findings: In diverse species transcription factors belonging to the forkhead/winged helix box gene, group O (FOXO) subfamily have been found to be crucial in downstream suppression of the life-shortening effects of insulin/insulin-like growth factor-I receptor signalling pathways that, when upregulated, accelerate ageing by suppression of FOXO. The various adverse processes activated upon FOXO suppression include increased generation of reactive oxygen species (ROS). ROS are pivotal for the onset of various common conditions, including hypertension, atherosclerosis, type 2 diabetes, cancer and Alzheimer's disease, each of which shortens lifespan. In humans, FOXO3a, as well as FOXO1 and -4, and their downstream effectors, could hold the key to counteracting ageing and common diseases. An understanding of the processes controlled by these FOXOs should permit development of novel classes of agents that will more directly counteract or prevent the damage associated with diverse life-threatening conditions, and so foster a life of good health to a ripe old age. Just like caloric restriction, lifespan can be increased in various species by plant-derived polyphenols, such as resveratrol, via activation of sirtuins in cells. Sirtuins, such as SIRT1 in mammals, utilize FOXO and other pathways to achieve their beneficial effects on health and lifespan.

Conclusion: Lifespan is tractable and basic mechanisms are now known. Longevity research complements and overlaps research in most major medical disciplines. Current progress bodes well for an ever-increasing length of healthy life for those who adapt emerging knowledge personally (so-called 'longevitarians').

I think the author coined "longevitarians," since that's the first time I've heard it, but we'll let that pass. The rest is quite to the point - and the more scientists who stand up to say it, the better. We know more than enough to make a serious start on the fight to cure aging! If you would like to learn more about the science here, you can find a very educational discussion on FOXO and related areas of genetics in a Fight Aging! post from early 2004.

SENS 2 Early Registration Deadline, June 15th
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If you want to get in under the early registration deadline for the Second Strategies for Engineered Negligible Senescence (SENS) Conference in September then you are cutting it fine - your chance to save money on the registration fee is gone after June 15th.

The purpose of the SENS conference series, like all the SENS initiatives (such as the journal Rejuvenation Research and the Methuselah Mouse Prize), is to expedite the development of truly effective therapies to postpone and treat human aging by tackling it as an engineering problem: not seeking elusive and probably illusory magic bullets, but instead enumerating the accumulating molecular and cellular changes that eventually kill us and identifying ways to repair - reverse - those changes, rather than merely to slow down their further accumulation.

The SENS 2 program as it stands right now promises a good conference - you'll see many familiar names and promising fields of science if you're someone who keeps tabs on biogerontology and other aging research. The Ellison Medical Foundation session on the removal of intracellular waste products - a growing area of interest in the medical research community - looks to be particularly fascinating.

Also of note:

This year's SENS Lecture, provisionally entitled "Stem cells, SCNT and the rejuvenation imperative", will be given by Dr. Michael West, CEO of Advanced Cell Technology.
NIH Roadmap For Nanomedicine
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The NIH has added nanomedicine to its roadmap initiative for medical research. "What if doctors could search out and destroy the very first cancer cells that would otherwise have caused a tumor to develop in the body? What if a broken part of a cell could be removed and replaced with a miniature biological machine? What if pumps the size of molecules could be implanted to deliver life-saving medicines precisely when and where they are needed? These scenarios may sound unbelievable, but they are the long-term goals of the NIH Roadmap's Nanomedicine initiative that we anticipate will yield medical benefits as early as 10 years from now." Nice to see that medical nanorobots as proposed by Robert Freitas are on the agenda front and center.

Link: http://nihroadmap.nih.gov/nanomedicine/

Never To Late To Exercise
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(From Health 24). On slow news days, I like to remind folks about the health basics - things you should be taking care of today if you want to be active and alive to see the future of real, working anti-aging medicine. "Exercise helps maintain and, in some cases, improve bone mass in people aged 55 to 75." Bone density loss through osteoporosis is a major problem - and while therapies are in the works, they certainly aren't here today. You should not expect future science to rescue you from the results of neglecting your health - maybe you'll get lucky, maybe you won't. Given the sorts of healthy life extension science we expect to see in decades ahead, it would be a shame to miss the boat - die, in other words - because you didn't take care of your health today.

Link: http://www.health24.com/news/Ageing/1-888,32121.asp

Stem Cell Banks From Teeth?
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From Sci-Tech Today, an article on stem cells obtained from teeth - a topic I have touched on previously - and the creation of stem cell banks for these cells. The consensus from the business community appears to be that it's too early to tell whether these cells are in fact useful enough to bank. From Robert Lanza of ACT: "The real question comes down to whether or not it warrants the resources, and I think it would be premature at this point to start encouraging parents to start banking all these lost tissues from their children. As the stem-cell field advances, other strategies will pan out ... In a way, it could be taking advantage of parents who might do it out of guilt or lack of information. I think a parent would go crazy if they tried to collect stem cells every time their child lost a tooth, some hair or some blood."

Link: http://www.sci-tech-today.com/story.xhtml?story_id=02200000H3S2

Boosting Macrophages
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Medical News Today reports on hints of a new way to tackle age-related conditions caused by a build-up of cellular waste in the body. "Using blood samples, investigators found that in healthy people, cells belonging to the innate immune system called macrophages, cleared amyloid-beta in a test tube test developed at UCLA. However, the macrophages of some Alzheimer's patients could not adequately perform this cleaning job. ... this immune defect may also be present in other diseases where a build-up of waste and plaques occur, such as in cardiovascular disease and Gaucher's disease. ... If further study shows that this defective macrophage function is present in most Alzheimer's disease patients, new hormonal or immune-boosting approaches may offer new approaches to treating the disease."

Link: http://www.medicalnewstoday.com/medicalnews.php?newsid=25934

Calorie Restriction Blogs
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Calorie restriction blogs are starting to spread - I think that this is a very good thing. The practice of calorie restriction with optimal nutrition (CRON) is as simple as a rock on a table once you have some experience; with the requirements of a calorie count and an optimal nutrient intake in hand everything else tends to fall into place and become obvious. Getting to the point of being experienced has always been the question mark in the process, however. What foods, what methods, what are the common stumbling points ... what exactly do I do today? A good calorie restriction blog is a real help for those working their way into the practice of this lifestyle option for healthy life extension. Here are some for your reading pleasure:

From Ian Clements
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In the last Longevity Meme Newsletter I offered the following opinions on Protandim, current research into tuning the human metabolism and other longevity-related tinkering:

It is somewhat frustrating to watch well-oiled publicity machines going to work to promote what is essentially useless junk in the grand scheme of things. There is some moderately interesting science in the intersection of metabolism and longevity at the bottom of all this, but it's not science that will deliver firm answers or meaningful progress any more rapidly than the folks currently working - from a far more sound scientific basis - on calorie restriction mimetics. It certainly won't deliver any surety in whatever bottled compound they're selling today.

As I've remarked before, the whole field of metabolic science is useful, but any healthy life extension to come from it will be a form of tuning the machine - using better motor oil, running the engine at the most efficient speed, that sort of thing. This suffers from much the same problems as supplementation - you can spend as much time and money as you like tinkering and experimenting ... are you ever really sure you are making progress? Is it a productive use of your resources once you have gone past the basics?

Ian Clements wrote to me with the following comments:

This has, for me, highlighted the two differing models (which are not necessarily mutually exclusive) which may be a source of confusion: on the one hand, we may already be immortal, but are held back from achieving this by a myriad of successive minor failures of our body system; on the other, we have already more or less reached our natural life-span limit with our traditional living methods, and therefore need a radical alteration (growing replacement organs like lizards; reversing the present gradual decline of complete replacement of failing sub-systems).

It is not clear (to me anyway) which of these models more correctly describes us (or any living organism for that matter).

If the former, let's call it Model A, is true, then addressing each and every issue as it comes up or for which new solutions are found may well enable us individually live longer and the average life span to increase. This approach appears to be the one which has worked for the last 100+ years, and explains the data of a linear increase of the numbers and percentages living beyond 100 years. Model A is probably the one most of us use at present in practice, as we incorporate each successive proven (or plausable) new method and life-style alteration (regular exercise, not smoking, anti-oxidants, etc).

Model A was/is based on the belief that we can extend our healthy life up to an implicit maximum, but not extend beyond that - this last phrase is the one I now wish to challenge (implicit in its turn, byt the linear extension of lower mortality rates beyond about 80). However, we can revise our view of Model A (to the status of Immortality model): that is, immortality can be achieved by incorporating (cautiously) each and every proven improvement as they come along and therefore (perhaps) stay ahead of the ageing processes otherwise taking place.

The additional (Model B) idea recently introduced is the lure of immortality by some radical new methods - such as growing new organs from our existing cells (as distinct from transplants) to replace failing/ageing ones. I also put CR mimetics in this class, as this would probably require a lifelong intake of some drug to cause our cells to do the mimicing.

One of the benefits of age is that you get experience of many things, as distinct from just reading about them. And one of the things I've become increasingly convinced about is that gradual change/evolution is more successful than radical or revolutionary change. As a scientist, I have an open mind and will let the evidence decide; but until that happens (either way), I'll use the step-by-step approach to life extension (as, I'm sure, most others will). What I am highlighting here is that there needs to be a more explicit recognition of the two alternative models, and to be aware that Model B is not the only game in town - that Model A should not be either dismissed or consigned to the band-aid category; it just might be the only one that works.

Thus, far from tinkering being only a process of minor improvement whilst awaiting the Holy Grail of a radical complete solution, it (Model A) may be the only solution. If so, then far from needing to get started on anti-ageing research, we are already within the midst of it - after all, doubling the average age of death (well, 25%-50% if we ignore the distortion of including the under 5s mortality figures) in a hundred years is not to be sniffed at; couple that with the healthier old and linear improvements in mortality figures above 75 or so for several decades indicates that Model A has 'legs'.

Immortality in these comments refers to physical immortality, a state of "vulnerable agelessness."

I think I could assign all valid scientific efforts to extend healthy life span to the category of gradual change - but some gradual change is faster than others. No-one is claiming that Aubrey de Grey's Strategies for Engineered Negligible Senescence (SENS) could happen overnight; advances would be gradual ... but I see such work as more effective on a per dollar investment basis than working with supplements and metabolism. As is pointed out above, it's not a zero-sum, mutually exclusive sort of choice, however - in fact, everything that is not SENS is pretty well entrenched in the private and public research communities already. It's just that the resulting - largely incidental - gains in life span are not enough, and show no signs of accelerating rapidly. We need to add further, better strings to our bow if we want to avoid the consequences of untreated degenerative aging.

Fetal Stem Cell Heart Therapy
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(From PR Newswire). The Barbados-based Institute for Regenerative Medicine has published results from recent work carried out in Ecuador: "This is the first-ever study to use human fetal-derived stem cell therapy in patients with heart failure and, though from a small group of patients, the results are very compelling and demand additional research ... It was especially gratifying to see these patients, many of whom couldn't walk more than a short distance without losing their breath, improve their ability to perform physical activities that are a part of everyday living." The results appear similar to those of initial trials of adult and embryonic stem cell therapies for heart damage from the past few years.

Link: http://www.prnewswire.com/cgi-bin/stories.pl?ACCT=109&STORY=/www/story/06-06-2005/0003818053&EDATE=

Stem Cell Therapy For Stroke Damage
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Promising news from ABC: "South Korean researchers say they have successfully used stem cell therapy to treat brain-damaged stroke victims and others who have suffered similar organ damage. ... The team says it has extracted stem cells from the bone marrow of the patients, whose condition was caused by clogged blood vessels leading to brain or other organ damage. They then injected the damaged organs with the stem cells. ... The function of those (impaired human) organs was found to improve significantly after they were injected by the stem cells ... It says that three of five cerebral-infraction patients who have been treated 'improved significantly in terms of linguistic impediment.'"

Link: http://www.abc.net.au/news/newsitems/200506/s1388885.htm

Reinforcing Reliability Theory
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The Reliability Theory of Aging provides a powerful lense through which to view other research. Take this piece from EurekAlert on chronic illness, inflammation and what is effectively an increased rate of degenerative aging: "Older women with chronic cytomegalovirus (CMV), a lifelong viral infection, were found to have more than triple the risk of being frail than those who did not have the infection ... Further data showed that women who had both the viral infection and high levels of interleukin-6 (IL-6), a marker of inflammatory response, were even more likely to be frail than those who had either alone." Our bodies are complex machines; like any machine, those subject to greater rates of damage will tend to degenerate and fail more rapidly. This is why some historical gains in life span can be attributed to widespread reduction in chronic disease.

Link: http://www.eurekalert.org/pub_releases/2005-06/bpl-cim060805.php

Calorie Restriction Papers
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Papers on calorie restriction and its underlying mechanisms for healthy life extension are in press for the latest Mechanisms of Aging and Development journal - a special issue focused on this topic. Of note is Calorie restriction and SIR2 genes - Towards a mechanism by Leonard Guarente (cite doi:10.1016/j.mad.2005.03.013):

Calorie restriction is the first and most compelling example of life extension in mammals. Much speculation about how CR works has focused on ideas of what causes aging. Since these causes themselves are much disputed, I have instead focused my thinking on lessons from simple model organisms, which have emerged from recent genetic studies. These findings can now be integrated with numerous, elegant studies on CR over the decades, which provide a treasure trove of information about physiological changes that are elicited by this regimen. In this paper, I present data showing that the SIR2 gene is a strong candidate to regulate CR in the simple model organisms, such as yeast and Drosophila. I then summarize what is known about the mammalian Sirt1 as it relates to physiological changes during CR, and discuss how this mechanism may impact on life span, as well as diseases of aging.

There are a large number of other abstracts well worth perusing for those interested in closely following progress on aging and longevity research.

Cellular Control Is Key
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You'll excuse me, I hope, for continuing to belabor the point that advancing knowledge of cellular genetics and biochemistry - and the subsequent application of that knowledge to control our cellular processes - is one of the most exciting areas of mainstream medical science at the present time. The new technologies of bioinformatics are driving basic research ever faster; the closer we look at the mechanisms of our own cells, the closer we get to directly addressing the roots of disease, cancer and aging. Get thee hence and read what Randall Parker has to say about one small part of this process - steps on the road to reverse engineering the workings of stem cells.

Link: http://www.futurepundit.com/archives/002817.html

MicroRNAs, Stem Cells, Cancer, Cellular Immortality
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I thought I would direct your attention to a nice article on current scientific interest in microRNAs:

One of the medical marvels of stem cells is that they continue to divide and renew themselves when other cells would quit. But what is it that gives stem cells this kind of immortality? Researchers report in the journal Nature that microRNAs - tiny snippets of genetic material that have now been linked to growth regulation in normal cells as well as cancer growth in abnormal cells - appear to shut off the "stop signals" or brakes that would normally tell cells to stop dividing.

As soon as you're down in the depths of cellular mechanisms, you run into links to both cancer and aging:

In a commentary, Dr. Paul Meltzer of the National Human Genome Research Institute said microRNAs "are now definitely linked to the development of cancer."

...

And now that the researchers have found that too few microRNAs are bad for stem cells, they want to see what an abundance of microRNAs will do. Perhaps the right recipe can give even ordinary cells a touch of "stem-cellness."

"We are right now testing that, by overproducing microRNAs in the daughter cells that have begun to differentiate," Ruohola-Baker said. "Maybe this would also help aging stem cells. Maybe you can keep them dividing by using more microRNAs."

Other recent work demonstrates that helping aging stem cells would certainly be a good thing insofar as health and longevity are concerned. Human cells are basically finite state machines on a number of different levels. The only difference between an embryonic stem cell and an adult, differentiated cell lies in the state of the inner machinery (give or take a few gross oversimplifications). The more we understand, the more we can do - we are presently in the very earliest days of a medical revolution, but at the far end of the path of complete cellular control we will have cures for all diseases ... and for degenerative aging itself.

Towards Gene Therapy For Arthritis
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As Betterhumans notes, scientists are moving towards the use of gene therapies for age-related inflammation and autoimmune disorders such as arthritis. The first, early trials have taken place or are underway: "Gene therapy can be used to treat rheumatoid arthritis and other chronic conditions, suggests a new human trial. ... Up to five years later, the researchers report, there are no clinical side effects and no signs that the gene-carrying vector - a modified retrovirus called Maloney Murine Leukemia Virus - has become capable of replication in the patients. ... Results showed that genetically modified cells had high levels of IL-1 Ra. Furthermore, clusters of cells that expressed large amounts of the gene were present at the surface of the synovial tissue and produced far less inflammation-provoking chemicals."

Link: http://www.betterhumans.com/News/News/tabid/61/News/705/Default.aspx

More On Stem Cell - Cancer Connection
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Understanding the biochemistry underlying the way in which cancer makes use of stem cells to grow will lead to much more effective therapies and prevention. From Medical News Today: "Like a siren song, breast cancer secretes growth factors to attract stem cells then uses those cells - which normally promote healing - to help it survive, researchers have found. In the laboratory, the researchers have documented secretion of growth factors FGF2 and VEGF by breast cancer cells, seen these factors bind to receptors on stem cells then watched stem cells migrate toward the cancer. When they took the growth factors away, the deadly migration decreased." This research should also increase our understanding of how to control stem cells for new and better regenerative therapies.

Link: http://www.medicalnewstoday.com/medicalnews.php?newsid=25797

Glancing at the World Health Network
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The World Health Network is the online face of the American Academy for Anti-Aging Medicine (A4M), yet another of the predominantly old school organizations in the wider healthy life extension community that leave me with mixed opinions. I have been watching A4M beat their online presence - a website with a respectable Alexa traffic rank of 52,000 or so - into shape over the past few years. Over that time, the face of A4M as represented by their website - and interviews with the founders in the mainstream media - has evolved to present a much more forward-looking, responsible perspective. Less hormone therapy and supplements, more stem cells, genetics, and modern medical research. I think this is probably best encapsulated by a glance at their front page news headlines and their comparatively new (re)definition of anti-aging medicine:

Anti-aging medicine, an extension of preventive health care, is the next great model of health care for the new millennium. This model is based on the early detection, prevention, and reversal of aging- related diseases. All diseases fall into four categories; the first three-inherited genetic disease, infectious disease, and trauma-account for only 10% of the cost for treating all disease in America. Ninety percent of all health care dollars are spent on extraordinary care in the last two to three years of life. A grand total of fifty percent of the US health care budget is spent on the degenerative diseases of aging [Health Care & Finance Administration, 1996.] One hundred million Americans are currently being treated for one or another degenerative disease at a health care cost of more than $700 billion per year. If we really want to make an impact on health care in this country and in the world, we must focus on the degenerative diseases of aging. If we can slow aging, we can eliminate more than 50% of all disease overnight. We can alter this dreadful course by preventing, delaying, or reversing the diseases associated with aging.

As I've said before, A4M says a lot of the right stuff and their hearts do appear to be in the right place - it's their implementation that leaves much to be desired. While I would like to be able to claim some credit for pushing their public outreach in this direction (you'll notice Longevity Meme RSS feed content showing up on the World Health Network occasionally, and this new definition surfaced around the time I published "What is Anti-Aging?"), I'm sure they've arrived here largely of their own accord and by watching the success of others far more vocal and influential than myself.

It remains to be seen just how deep this exterior gloss will penetrate into the organization; the A4M core business relies of conferences and association with the less reputable side of the marketplace. This continues to be a bone of contention and - I believe - ensures that A4M brings as much harm as help to the future of healthy life extension.

As a final thought, it is the desires of the public that ultimately shape for-profit organizations. Even those for-profits that cater largely to other businesses - such as A4M - are a great deal more responsive to public opinion (as expressed in dollars and page views) than anything else you might find out there. You can pass on your opinion loud and clear by being an educated, aware, vocal customer. Vote with your wallet; don't buy products branded as "anti-aging." Write outraged letters to businesses that are clearly jumping on the "anti-aging" bandwagon and insulting your intelligence. Support medical research and organizations that take a responsible attitude towards longevity and aging research. Talk loudly about your choices as a consumer and why you are making them - ultimately, those business ventures that succeed determine the look of an entire market. We - people like you and I - decide which business ventures succeed via our choice of where to spend our time and money.

In short, you have a great deal of power in these matters - make use of it.

Progress In Controlling Differentiation
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Advances in our understanding of stem cell differentiation are starting to crystallize into hardware, software and technology platforms - an important step towards expanding the field of regenerative medicine and developing more sophisticated therapies for age-related conditions. Genetic Engineering News reports on a chip-based technology to control adult stem cells: "The solution we are pursuing is to build a device that can interact with the stem cell at the micro- and nanoscale. For example, exposure to minute amounts of chemical at the appropriate time and place could be the key for guiding stem cells isolated from fat tissue to turn into cartilage or bone constructs. ... Ultimately, surgeons could use this product to grow heart tissue in the Emergency Room to replace damaged tissue resulting from a heart attack."

Link: http://www.genengnews.com/news/bnitem.aspx?name=543457XSL_NEWSML_TO_NEWSML_WEB.xml

Scientific Conquest of Death Review
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The CBCNetwork is running a rather interesting review of The Scientific Conquest of Death: Essays on Infinite Lifespans, written by someone clearly in the pro-death camp but with a more open mind than most. It serves as both a recommendation and as a fascinating insight into the mindset of people who literally cannot see a future for healthy life extension. From within our supportive but oftimes insular community, it is easy to forget just how much work is left to do in education and advocacy for longer, healthier lives. Too people out there in the world don't yet understand that radical life extension is within sight - all the more reason to speak out in support of longevity research.

Link: http://www.thecbc.org/redesigned/research_display.php?id=227

Why Live A Longer, Healthier Life?
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Why do you want to live a longer, healthier life? Why do you want to see age-related degeneration consigned to the dustbin of history? What are you doing to make this future a reality? If you have a powerful, compelling answer to these questions, then the Betterhumans crew wants to hear from you. "We want to know what you think about life extension, and what you're doing to live longer and healthier. To this end we're holding The Fantastic Voyage Life Extension Blog Contest. Four winners will each receive a copy of Fantastic Voyage, as well as have their entries showcased. ... The contest is open from June 6, 2005 to June 20, 2005." Speaking out in support of healthy life extension is a vital part of ensuring a better future - so get out there and practice!

Link: http://www.betterhumans.com/Forums/tabid/55/forumid/7/postid/248/view/topic/Default.aspx

Advancing Cellular Understanding
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From a long-term perspective, the most important outcome of embryonic stem cell research is a greater knowledge of cellular processes, genetics, biomechanics - and how to control them. This is the foundation of the next generation of medical science, progress far beyond near-future cures for age-related conditions. The Washington Post reports on progress towards creating embryonic stem cells without the use of embryos. "As cells mature during embryonic and fetal development, certain genes in those cells are switched either on or off. Depending on the new pattern of activity, each cell becomes skin, heart muscle, nerve or some other kind of specialized cell. Now scientists are exploring methods for resetting the genetic switches inside various cells to the positions that will make them embryonic again."

Link: http://www.washingtonpost.com/wp-dyn/content/article/2005/06/05/AR2005060500872_pf.html

Embryonic Stem Cell Research As a Proxy For Healthy Life Extension
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Nick Gillespie notes at Hit & Run:

leading opponents to embryonic stem cells are not simply worried about the embryo issue - they fundamentally question whether we should be intervening to prolong and improve human lifespans and ameliorate human suffering.

...

George W. Bush's bioethics kingpin, Leon Kass, is on record as saying, "The finitude of human life is a blessing for every individual, whether he knows it or not." Like Fukuyama and others that Reason's Ron Bailey has pegged as "pro-death," the core issue is not how we might extend life but whether we should.

As I've pointed out in the past, it is hard to even hold a debate with people who push the horrific concept of using government power to block research and treatments for age-related degeneration. It amounts to promoting murder by legislation.

Glenn Reynolds echoes Nick Gillespie's view, made in response to the latest in embryonic stem cell research:

This would defuse the pro-life opposition. It wouldn't address the concerns of those - like, say, Leon Kass - who are uncomfortable with dramatic advances in medical technology for other reasons.

Both give too much respect for these views; there comes a time when you have to stand up and tell the other side that they are far outside the bounds of discourse. You can't hum and nod thoughtfully in response to a proposal that involves forcing billions to suffer and die.

The Perils Of Public Funding
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There are good reasons as to why public funding is horribly inefficient - perhaps as much as fifty times less efficient than private funding in a competitive environment. Equally, there is the matter of hidden costs - how much time and money has been spent on California's stem cell initiative to date? In a more libertarian society, supporters would just get on with raising the money to go directly towards research - which would be off and running already. Instead, we are stuck with endless resource-draining battles over control and politics ... and comparatively little actual research. This update on said battles is from the Washington Post.

Link: http://www.washingtonpost.com/wp-dyn/content/article/2005/06/05/AR2005060500650_pf.html

SAHF, Cancer And Aging
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From the LEF News, a short piece that is illustrative of the present day intersection of genetics, molecular biochemistry, cancer and aging research. "As cells reach senescence, an alteration in chromatic structure called senescence-associated heterochromatin foci (SAHF) silences the genes that trigger the cells growth. ... SAHF are domains of tightly packed chromatin that repress activity of the genes that normally trigger cell proliferation. [Researchers] have identified at least three proteins in the cell that contribute to the formation of SAHF. ... This research suggests the possibility that PML arises because the PML protein is not able to do its job in forming SAHF. If this is true, this study might help in the design of therapeutic drugs to treat cancer patients and even lessen some aspects of aging."

Link: http://www.lef.org/news/LefDailyNews.htm?NewsID=2272&Section=AGING

More On Alzheimer's, Plaque Removal
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Promising research into Alzheimer's is reported at InfoAging: The brain cells in a mouse model of Alzheimers disease (AD) recovered rapidly after the characteristic brain plaques were removed ... The researchers injected the mice with an antibody for a key component of brain plaques, the amyloid beta (Abeta) pepide. In areas where the antibodies cleared the plaques, many of the swellings observed on nerve cell branches rapidly disappeared. Prior to the experiment, many scientists believed plaque damage to nerve cells was something that only needed to happen once. The new findings suggest that the plaques might not only cause damage but also actively maintain it." This is good news for groups currently working on Alzheimer's vaccines designed to attack the plaques.

Link: http://www.infoaging.org/news_article.html?SMContentIndex=2&SMContentSet=0

Blogging the AGE Meeting
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Pete from supplement company Relentless Improvement has announced that he will be blogging from the 34th annual meeting of the American Aging Association and 19th annual meeting of the College of Clinical Gerontology at the Marriott City Center in Oakland, CA. The first two entries are up already. His commentary comes from a supplement industry point of view, needless to say, but since none of the rest of us are there to blog about the conference, good for him for taking the time to do so.

One thing I learned - there is no shortage of disagreement on any given view. Keep in mind the folks here were all at least PhD's, and most of them working on the very bleeding edge of research. Another surprise, just how little is known about the aging process. I am sure the majority of physicians are fine, hard working people, but they simply cannot keep up with all the latest breakthroughs. The goods news is that a wide variety of things are being looked at in the anti-aging field.
The Future Is In Simulation
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To revisit a topic I have explored at Fight Aging!, the future of biomedical research - faster, cheaper, better, open to non-professionals - is in simulation. Why run all your experiments in the real world when you can run ten times as many at a fraction of the cost in a computer system? Not to mention that the curve in processing power costs means that you'll have twice the experimental capacity at the same price a few years down the line - and that many more organizations can contribute to advancing science. This article from Medical News Today looks at one of the forerunners of future simulational research software; healthy life extension advocates will begin to effectively organize their own research in the years ahead as the costs keep falling.

Link: http://medicalnewstoday.com/medicalnews.php?newsid=25599

Jay Fox Ponders Protandim ... and Spending Your Money Wisely
Permalink | | Posted by Reason

Well, I'm happy to report a shiny silver lining to this sudden barrage of Protandim-related marketing and nonsense - it has provoked the always worthwhile Jay Fox into writing another of his excellent blog-essays on the effectiveness of "anti-aging" therapies:

This discussion actually comes at a fortuitous time, because of an article recently written by renowned biogerontologist Aubrey de Grey. In his article, de Grey questions the idea of trying to measure the "rate of aging", since nearly all currently or hoped-to-be used methods of measuring the rate of aging are inherently flawed, and will essentially be useless in the long term.

I know you came here to read about Protandim, but let's digress a bit on a tangent related to measuring the effectiveness of so-called "anti-aging" pills: Gompertz Law. I promise it'll make sense, eventually...

It's well worth your time to read; hopefully it should help put the light and noise surrounding comparatively trivial items like Protandim into a better context. He makes many of the points that I was aiming for in my commentary on Protandim - namely that it's a drop in the bucket, and that chasing the drops is a bad idea when the same level of effort will eventually produce streams or rivers of progress in medical science, longevity and real anti-aging therapies.

So what should we make of Protandim? Well, to date, the only intervention (short of genetic manipulation) shown to significantly decrease the slope of the Gompertz Curve (and thus, likely add a lot of extra years to the lifespan of young people) is calorie restriction. Of all the other chemicals found to increase lifespan, most do so simply by shifting the Gompertz Curve down.

...

If all that Protandim can accomplish - and until long-term studies are carried out, the best we should hope for - is to shift the Gompertz Curve down, then an older person will see about as much benefit as a younger person: a modest, perhaps even small, absolute increase in remaining years before death.

...
So if you have money to spend, and you're considering spending it on Protandim, please consider helping out a cause that will one day make aging itself a thing of the past. Please donate to the M Prize!

I couldn't have said it better myself.

A Start On Biomolecular Nanomachines
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(From Medical News Today). It's never too early to start in on the research that will lead to medical nanorobots of the sort envisaged by Robert Freitas. Advanced nanomedicine will take over from regenerative medicine as science progresses further down the path of extending the healthy human life span - but we are only just getting started today. The first research projects into "wet" nanorobotics are all about developing a technology base on which to build therapeutic applications; this is the work of decades, all told. For more information on the likely future of these technologies, you might want to read Chris Phoenix's "Nanotechnology and Life Extension."

Link: http://www.medicalnewstoday.com/medicalnews.php?newsid=25587

Aubrey De Grey At Stanford, June 8th
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(Via the Stanford Transhumanist Association). For those of you in the area, biogerontologist Aubrey de Grey will be speaking at Stanford University next week, June 8th. "Many people say curing aging might be a bad idea, but deep down we all know that's nonsense. We cling to silly doubts about it only because we don't want to get our hopes up too soon. Eventually, though, this will stop being appropriate: we'll know enough to wage a 'war on aging' with a fair chance of winning it in a few decades. At that time, ambivalence will costs lives - 100,000 lives each day - by slowing down the research and development to turn our knowledge into working rejuvenation therapies. I will explain that we have recently reached that point: the time for the war on aging has arrived."

Link: http://www.stanford.edu/group/transhumanism/blog/archives/2005/06/aubrey_de_grey.html

Yet More On Lifeline, Protandim
Permalink | | Posted by Reason

It seems that Lifeline Therapeutics, marketeer for Protandim, has netted venture capital:

Lifeline Therapeutics, Inc. (OTCBB: LFLT), a health company dedicated to developing products that help people live better, healthier and longer lives by fighting oxidative damage in the body, today announced the company completed an $8 million private placement. Keating Securities, LLC acted as sole placement agent of the financing. Proceeds from this funding will be used to eliminate the Company's debt of $3 million, for U.S. research surrounding its Protandim product and as working capital related to the development of new antioxidant therapies.

Through the miracle of product placement - available to those bearers of the magic green tokens we call "money" - this coincides with a nice healthy examination of Protandim and supporting science at ABC. Such is the way the world works, nothing out of the ordinary there.

What makes me a little more skeptical than normal when it comes to pills and anti-aging claims is the history of this particular company. The short version can be told as follows:

  • CereMedix tests a compound that could extend life span by mitigating oxidative stress. This is CMX-1152, described on the CereMedix website (scroll down a bit on that page).
  • Lifeline is founded on the basis of a licensing deal with CereMedix; the Protandim name is later assigned to CMX-1152
  • Around this time, I begin to comment on this deal, CMX-1152, Protandim and Lifeline. Some of my comments are promptly misquoted, rewritten and used as a glowing endorsement on the Lifeline website; not an auspicious start. My grumbling on that topic can be seen in the Immortality Institute thread on Lifeline.
  • For reasons that remain unclear, Lifeline does not proceed with CMX-1152, but rather begins looking for a new product to market under the existing brand name of Protandim.
  • For a time, Lifeline continues to use the experimental results from CMX-1152 to tout their new non-CMX-1152 product, which could charitably be described as a potpourri of existing antioxidant supplements. This also is documented in the the Immortality Institute thread on Lifeline. Not cricket, gentlemen.
  • Now we see a more mature offering from Lifeline, at least in the marketing department. They have retained the focus on oxidative stress, but are building a brand on the work of different scientists.
  • So far as it goes, it looks like Lifeline is still selling the potpourri of existing supplements.

So, this is just like the circus over resveratrol by the looks of things; some moderately interesting science in the intersection of metabolism and longevity buried by a cartload of marketing. We may, or may not, find out something interesting about the long term effects of the product on humans in a decade or so. As for resveratrol, I have no doubt some folks will make money from Protandim, but this is a distracting sideshow for anyone interested in meaningful healthy life extension. The immediate future of health and longevity is not in pills, folks. There isn't anything out there proven to do better than simple calorie restriction - and even that isn't so great in the grand scheme of what is possible. If you want to live a much longer, much healthier life, don't spend all your time chasing after better pills and tinkering with your metabolism. Instead put your energies into supporting the sort of research that will put an end to age-related degeneration once and for all - that could happen within our lifetime, but only if we stand up and make sure of it.

UPDATE: Some interesting comments from Pete Estrep:

Well, they certainly have guts to present the data on this web page, http://www.protandim.com/scientific-studies.htm

Around thirty mice and thirteen subjects in the human trial. They draw a line through points that have an R^2 of 0.02. This means that the points are almost randomly scattered. Sure, you can draw a line through these points but it is almost meaningless. I won't be buying Protandim until they generate a lot more data.

FYI, the stuff is made of herbs (ashwagandha, and extracts of milk thistle, bacopa, green tea, and turmeric). They claim it works by increasing levels of protein antioxidants. If this is true I am interested in the mechanism since you can increase levels of endogenous antioxidants by increasing oxidative stress and damage. This is similar to certain claims of compounds increasing levels of DNA repair enzymes. The most reliable way to do this is to increase DNA damage because you will get elevated levels of repair enzymes in response to damage. The effect Protandim has on lipid peroxidation is irrelevant since lipids are replaceable, it is just a proxy for damage to more precious stuff, like DNA.. What we really want to know is what Protandim does to the rate of DNA damage. Does it cause less damage, more, no change? Unknown.

Biotech, Finally
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BusinessWeek provides insights into privately funded medical research - a busy, fascinating realm of human endeavor that the mainstream media largely ignores (most likely because reporting on it requires actual work). "Medical care is reaching a tipping point. Not that most patients will be healed right away -- the vast majority of sick people continue to dose themselves with tiny bits of chemicals, otherwise known as pills, that represent medicine's Old Guard. But the times are changing. The past 30 years of biological discoveries, insights into the human genome, and exotic chemical manipulation have unleashed a wave of biological drugs, many of them reengineered human proteins. These molecules have the power to change the prognoses for a huge range of diseases all but untreatable just five years ago."

Link: http://www.businessweek.com/print/technology/content/jun2005/tc2005062_4958_tc024.htm?chan=tc&

Pondering Inponderables
Permalink | View Comments (0) | Post Comment | | Posted by Reason

A slow news day, ergo you are treated to freeform musings on radical life extension from Glenn Reynolds over at Tech Central Station. "Would people who lived to 150 or 300 take time to retool? And, if they did, would they be as creative as they were when they were fresh out of school? I'm not sure. On the one hand, people who live to 300 can't expect to coast for a lifetime on the intellectual capital of their youth. And the opportunity costs in terms of lost time would be much lower as a percentage of lifespan than they are for a 55-year-old today." There's more in that vein, but think for most of us it boils to down to whether it is better to see for ourselves or to suffer and die - no contest there!

Link: http://www.techcentralstation.com/060105C.html

More On Protein Restriction In Flies
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The ever-useful Randall Parker has more on recent research into protein restriction versus calorie restriction in fly experiments. Be sure to look at Robert Bradbury's comment to the post as well:

There has always been some evidence that certain types of protein restriction may extend lifespan via mechanisms other than strict caloric restriction. One has to look at what caloric restriction probably does -- it probably decreases the production of free radicals from the mitochondria and therefore the downstream oxidative damage. However what protein restriction does is signal the upregulation of the recycling of proteins, esp. damaged proteins. So you can lower the ratio of damaged proteins to good proteins by either reducing the source of the damage or increasing the rate at which the damage is removed. Now, if some of the damaged proteins happen to be those in the mitochondria (which is likely to be the case) then protein restriction may increase the fraction of mitochondria with undamaged proteins which are less likely to cause free radical damage (damaged [sloppy] mitochondrial proteins increase free radical production).

Will this translate to humans? Who knows, and too early to say. Plain, vanilla calorie restriction still has robust science behind it for human health and longevity - but it's a far cry from any form of plausible and effective longevity therapy or radical life extension.

On People Who Want To Age and Die
Permalink | View Comments (6) | Post Comment | | Posted by Reason

I really don't have anything bad to say about people who are set on aging and dying - I just think that most of them haven't really thought it through, at least not to the point of understanding just how much personal suffering is going to be involved. (Which is why the old age simulation suit is such a great idea). We humans are just not all that well endowed when it comes to empathy and planning ahead. If we were, you can be sure that age-related degeneration and death would be solved problems already.

Regardless, there are still those folks who have thought it through and decided that aging and dying is for them. I'm certainly not one to argue against the value of freedom and personal choice, even if I'm quite sure that most of these people will make glad use of cures for age-related degeneration and death further down the line, despite having done nothing to help bring about this bright future of medicine.

No, the people I have a real problem with are those who seem set on forcing others to suffer and die. Personal acceptance of values that denigrate science and medicine and glorify suffering and death is one thing, but setting out to force the consequences of these views on others is nothing less than horrific.

Massachusetts Approves Stem Cell Research
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(From Boston.com). The winding path of stem cell politics in Massachusetts has ended - for the moment - with legislation permitting human embryonic stem cell research. There are rumblings about public funding, but "lawmakers refused to promise any follow-through on Travaglini's suggestion in March that the Legislature might earmark up to $100 million in stem cell-related research grants, infrastructure, and scholarship programs. With support for a large appropriation unclear in the Legislature, both legislative leaders said they want to size up how private investors respond to the new Massachusetts stem cell law before committing taxpayer money. ... Before the new law, scientists conducting embryonic stem cell research were required to seek the approval of their local district attorney."


Link: http://www.boston.com/news/science/articles/2005/06/01/stem_cell_bill_override_turns_talk_to_research_support?pg=full

Human Embryonic Stem Cells Stable
Permalink | View Comments (0) | Post Comment | | Posted by Reason

Welcome news from the Scotsman: "Researchers from Cambridge University appear to have cleared a major obstacle that may have scuppered hopes of using stem cells to repair damaged nerves and organs. They have shown that human embryonic stem cells are highly stable and not liable to undergo changes that could make them unsafe." As the article points out, the same is not true of embryonic stem cells in mice, which has caused some concern in scientific circles of late. "This was a surprise, because we know from mouse stem cells that these kind of genes are altered in the course of mouse embryo development. The fact that human stem cells are so stable is good news."

Link: http://news.scotsman.com/latest.cfm?id=4627714

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