Fight Aging!

Anti-Aging Medicine and Science notes that Aubrey de Grey will debate S. Jay Olshansky at BIOMEDEX 2005.

More than 500 participants from Canada, the United States and Europe, are expected to come hear the many prestigious speakers coming from all Four Corners of the globe. Amongst the latter, there will be S. Jay Olshansky, PhD, from the University of Chicago, and Aubrey De Grey, PhD, from the University of Cambridge, who will confront each others' opinions in a conference-debate on immortality, a utopia or a scientific truth?

For a taste of what this debate will look like, you might cast your eye to two articles from the BBC:

Aubrey de Grey - We will be able to live to 1,000
S. Jay Olshansky - Don't fall for the cult of immortality

The brief exchange of comments between myself, Aubrey de Grey and S. Jay Olshansky at the end of last year is also quite informative. The bottom line would seem to be that the only major bone of contention between the two scientists is over timescales relating to the implementation of healthy life extension technologies. This is a very important issue, however, as it ties into funding, public expectations and - ultimately - whether or not real anti-aging medicine is developed in time to save those of us reading this now.

Randall Parker notes that the importance of many recent advances in stem cell research lies not in the immediate results, but rather the new tools developed for the task. For example, with reference to differentiating stem cells into liver cells, "the more important story here is not the discovery of particular protein combinations that make stem cells differentiate into liver cells. What will be more valuable in the longer run is the ability to apply their technique to more combinations of of proteins to convert embryonic and other cell types into various desired cell types. With better tools progress can accelerate by orders of magnitude. This is another example of the accelerating rate of advance of biomedical research."

Link: http://www.futurepundit.com/archives/002600.html

Learning how to reliably control the differentiation of stem cells is an important step in developing new regenerative medicine for presently untreatable injuries and age-related conditions. EurekAlert reports on new progress in obtaining neural cells from embryonic stem cells. "Scientists have long believed in the therapeutic promise of embryonic stem cells with their ability to replicate indefinitely and develop into any of the 220 different types of cells and tissues in the body. But researchers have struggled to convert blank-slate embryonic stem cells into motor neurons, says Zhang. The goal proved elusive even in simpler vertebrates such as mice, whose embryonic stem cells have been available to scientists for decades." Work is proceeding on blood stem cell differentiation too.

Link: http://www.eurekalert.org/pub_releases/2005-01/uow-wsg012605.php

Sonia Arrison writes about the slow mainstreaming of transhumanism, a collection of ideas that includes strong support for greatly extending the healthy human life span.

William Safire bid farewell to his column at the New York Times this week, but not because he's retiring. Instead, this Pulitzer Prize-winning, former presidential speech writer is moving on to lead an organization concerned with what some call transhumanism.

Transhumanism is the advocacy of using life-enhancing technology to improve the human condition. It is a forward-looking philosophy, and savvy proponents spend a good deal of time thinking about the ethics involved in areas such as stem-cell research, genetic engineering, nanotechnology, and neuropharmaceuticals, to name a few.

...

America, and indeed the world, is entering a new age where significant advances in bio and nanotechnology might allow humans to live better and longer lives. But they might also change who humans are. Imagine if it becomes possible, as in the film Johnny Mnemonic, to integrate silicon into the brain so that memory is greatly enhanced. The question of whether that person is still human, and whether that matters, will be of utmost import from both a legal and cultural point of view.

The time to discuss these questions is now, so it is good to see the issues moving from fringe to mainstream. As Mr. Safire rightly points out, life expectancy for Americans has risen from 47 to 77 over the last century. Moore's law, that computer power doubles every two years, can be now combined with biotech. In the near future, we are all likely to be living much longer lives.

More than just discussing, we need to educate and raise awareness. The future of technological progress is not a track down which we move regardless of what people do - every inch must be worked for, paid for. If we all sit back and wait, expecting our lives to get longer, then we will simply wait until we die, the science left unaccomplished. While the nature of future technology that will lead to healthy life extension is fairly well understood at this time, directed research and funding into slowing, halting and reversing the aging process is lagging far behind. This must change.

A Newsweek article looks at some of the better known science relating to healthy life extension and the biochemistry of aging. We may still be on the ground floor of this field of research, but it's a very compelling ground floor and we know where to find the stairs up. As the public becomes more aware of what has already been achieved and what is thought to be possible, the demand for greater funding - private and public - for real anti-aging therapies should increase. Education, activism and advocacy are very important at this stage of the process. This scenario played out for cancer, AIDS and Alzheimer's funding - we should expect to be able to enact the same script for healthy life extension research.

Link: http://msnbc.msn.com/id/6884916/site/newsweek/

Early registration and abstract submission are open for the Second Strategies for Engineered Negligible Senescence Conference in Cambridge, UK. As organizer Aubrey de Grey notes, "the preliminary program already has 50 confirmed speakers, all of them
world leaders in their field. ... 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."

Link: http://www.sens.org/sens2/

The Los Angeles Business Journal takes a look at the current state of embryonic stem cell research in their part of the world. "At UCLA, researchers now working with stem cells from rats hope to one day fix damaged spinal cords and brains. Cedars-Sinai Medical Center researchers, using adult neural stem cells, are conquering brain tumors in mice, and researchers at the City of Hope are trying to grow human embryonic stem cells to produce human insulin. They're all hoping to secure some grant money from the newly formed California Institute of Regenerative Medicine, an outgrowth of Proposition 71." As the article notes, this research is still early stage: much improvement is needed in even the basic processes of managing stem cell lines and controlling differentiation.

Link: http://www.labusinessjournal.com/print.asp?aid=31500092.6734888.1093703.5514752.7597402.577&aID2=84122

ScienceDaily reports on experiments suggesting that low levels of radiation exposure increase longevity - in small mammals at least. This isn't of immediate practical value, but it adds to the body of knowledge surrounding hormesis, or the "phenomenon in which low doses of an otherwise harmful agent can result in stimulatory or beneficial effects." This study does suggest an underlying biochemical mechanism: "a moderate increase in glucocorticoid levels, associated with low-level radiation, could be an important factor underlying the increase in longevity that has been observed in other shorter studies on small mammals exposed to low-level radiation."

Link: http://www.sciencedaily.com/releases/2005/01/050128222047.htm

It looks like Jay Fox is getting a good reception from other quarters in the blogosphere. Good - I fully expect to see many more quality posts at Longevity First based on Jay's track record elsewhere. Some quality thoughts from Classical Values:

For starters, helping people to stay healthier longer is so self-evidently virtuous as to require no excuses. It angers me that such excuses are even thought necessary in "certain quarters". To live a good life requires, first and foremost, that you have a life to be good WITH. The dead have had done with being good.

But the life extension angle, isn't that just a little kooky? We have no proof at all that it's even possible, right? Aren't I just grasping at straws here? Well now, that's the funny thing. We actually DO have evidence that it's possible, at least in lab animals. Heck, it's not just possible, it's a done deal.

Worms have had their natural spans trebled, and quintupled. Rats have gained fifty percent. If the rat comes from a truly screwed up strain, prone to a short lifespan, caloric restriction can triple their life expectancy.

And we've known how to do this since the 1930's. It's only now that we have the tools to begin exploring the why of it.

Given these FACTS, when I hear someone denigrate this type of research as hopeless, or immoral, or doomed to failure, I ask myself where THEIR evidence is...but perhaps I'd better quit while I'm ahead.

Despite the successes in animal studies, we are still a fair way from engineering sufficient support for serious longevity research in humans. The technical obstacles are far less intimidating that the social obstacles and funding obstacles at this point in time - which is why advocacy is so important.

As a side note, keeping the conversation about healthy life extension alive and humming along is very much a part of broader efforts for activism and education. "Conversation" in this sense means that dispersed set of articles, commentary, opinions and back and forth in the online and print world; an emergent environment that reflects the level of interest and thinking in this topic. Fight Aging! was created to help that process along - I've been pleased to see that many other bloggers have joined in. By simply talking about healthy life extension in a public arena, we help our long term goals by making others aware of our ideas and the need for action.

Researchers are making great strides in the development of effective cancer therapies based on vaccines. Human trials have been undertaken in a number of countries with promising results to date. "The first U.S. kidney cancer vaccine trial is now underway at Columbia University Medical Center and NewYork-Presbyterian Hospital/Columbia. While the potential for vaccines to treat solid tumors has been recognized for more than a decade, this trial is pioneering the use of tumor immunotherapy - boosting the body’s natural immune system - as a way to fight cancer. ... Tumor vaccines contain a specific protein of the tumor cell that stimulates an immune response."

Link: http://www.cumc.columbia.edu/news/press_releases/kaufman_kidney_cancer_vaccine.html

The second part of Russell Blackford's examination of arguments "against nature" is up at Betterhumans. Those of us with an interest in living much longer, healthier lives often hear that our goal is "unnatural" and therefore somehow bad - how does this specious argument survive for in a world largely "unnatural" by the same criteria? Clearly deeper motivations are at work: "If technology is used to alter facts relating to these, such as by allowing for conception and birth without sex, or by promising us biological immortality, many people will feel that their sense of leading meaningful lives is threatened ... They are likely to express this sense by claiming that 'nature' is being interfered with - here, 'nature' is equated with whatever is seen in their particular culture as basic background conditions to human life."

Link: http://www.betterhumans.com/Features/Columns/Eye_of_the_Storm/column.aspx?articleID=2005-01-26-1

Phil Bowermaster of the Speculist has some interesting things to say about Jay Fox's piece on healthy life extension and advocacy entitled "Where's the Rage":

Our ancestors engaged in a war against death that we're still fighting today. They threw everything they had and everything they could think up at the enemy, and as a result we now have science and medicine and religion and, really, the whole of human culture. They were relentless and tenacious fighters, but (being rational creatures) they understood the limitations of the war they were able to wage. As a group, the clan/tribe/people would fight on until the end of time, making what progress they could against death. But as individuals, it had to be acknowledged that each and every soldier would one day fall to the enemy.

That was a terrible thing. An unacceptable thing. But it had to be accepted anyway. Refusing to acknowledge the inevitability of death would have made as much sense as refusing to acknowledge the inevitability of gravity. It was pointless, and you would go crazy if you thought too much about that kind of thing.

...

unfortunately, I think the only way we'll get to the point where people no longer "know" that death from aging is inevitable is when we have some very youthful 80-120 year olds who can attest to it personally. Yes, a lot of people will needlessly die between now and then. But again, we're talking about an unprecedented paradigm shift. Once we cross that particular chasm, my guess is that things will happen very fast. The rage that Jay is looking for will be awakened, and it will completely reshape our world.

You might recall that Phil has an article at the Longevity Meme that gives a good overview of his thoughts on the topic of aging and death. Personally, I think we can do better than Phil's guess at the future in that last paragraph above - the very existence of the anti-aging industry shows that people are very forward-looking and anticipatory in this matter.

Some interesting figures are provided in an article on stem cell transplants in NEWNews: "The University of Arkansas for Medical Sciences performed 633 blood stem-cell transplants in 2004, a number that officials say rivals the top facility nationally for blood stem-cell transplants." In short, the simplest form of stem cell medicine is already commonplace. "Physicians who treat cancer patients sometimes use blood stem-cell transplants to help rebuild infection-fighting white blood cells after chemotherapy. ... The actual transplant is usually an outpatient procedure that takes about 30 minutes ... These same cells that regenerate bone marrow will also regenerate heart muscle, nerve tissue, muscles, liver, bone, cartilage. The list gets longer every day."

Link: http://www.nwanews.com/story.php?paper=adg§ion=News&storyid=106141

(From Betterhumans). Increasing weakness and muscle decline are well known consequences of aging. Scientists are now delving into the biochemistry behind this degenerative process with an eye to preventing it. "There is a tight relation to how much muscle and strength a person has and (his or her) independence. There are many people who stand to benefit from this research. ... older women, aged 60 to 75, have difficulty building muscle mass despite weight training because they are unable to effectively reduce expression of the protein, myostatin. Myostatin is a protein made by muscle cells to block muscle growth. Scientists believe it plays a role in our early life, regulating muscle growth and ensuring normal development."

Link: http://www.betterhumans.com/News/news.aspx?articleID=2005-01-26-4

Jay Fox has been a prolific, thoughtful writer at the Immortality Institute forums for some time now. He's also involved with the M Prize volunteer group and efforts to start a Methuselah Fly Prize. After much arm-twisting, he's now blogging on healthy life extension at Longevity First. Add it to your bookmarks.

Perhaps the simplest and least controversial reason to pursue longevity first is that the other technology can wait.

I dream about space travel and mining the asteroid belt and colonizing the moons of Saturn just as much as the next technophile. But, I can wait a few decades to see those dreams achieved if it means that we can prevent a few hundred million people from dying who otherwise might not have to.

More to the point, I want to see those dreams of space exploration come true in my lifetime, and that merits spending vast resources on space technology. However, with an extended healthy life span, I can wait. If by curing aging, we can give people in their 40's and younger a pretty decent chance of living to 150, then we can all wait a few decades to invest those vast resources in space technology (or fusion power, etc.), and instead invest those vast resources into longevity research. In other words, we have so little to lose, and so much to gain, by making longevity research our highest priority.

We humans are an odd lot; so adaptive that we can live in the worst of circumstances, convincing ourselves that we have no choice in the matter and that worst must be best. Healthy life extension advocates have highlighted this aspect of human nature many times over - notably in Nick Bostrom's "Fable of the Dragon-Tyrant" - but still it remains a real barrier to the acceptance of serious anti-aging research and an acknowledgement that each of us can make a difference. Why accept aging, decrepitude and death when there is so much we could be doing about it? More than 100,000 people die each and every day from age-related conditions; where is the motivating rage at this horrific state of affairs?

Link: http://www.longevityfirst.org/archives/2005/01/where_is_the_ra.html

EurekAlert reports on the latest human trial for a first generation adult stem cell therapy. "Patients with severe congestive heart failure who had exhausted all other treatment options showed markedly improved heart function following a procedure in which their own stem cells were deployed directly into the heart by way of four tiny incisions in the chest ... All 15 of the patients who received stem cell injections had some degree of improvement, some with dramatic results." Scientists are still unsure of the precise mechanisms by which this type of stem cell therapy works, but it is certainly effective. Given the enormous number of people who die each and every day from varieties of heart disease, progress can't come soon enough.

Link: http://www.eurekalert.org/pub_releases/2005-01/uopm-sc012405.php

Tom FitzGerald notes via e-mail that the World Transhumanist Association will soon be working on a collaborative book:

The World Transhumanist Association is moving forward with the project to produce an essay anthology under the title "An Introduction to Transhumanism". As many of you know, I've volunteered to be the editor.

On a suggestion from Mike LaTorra, who is working on an essay on Transhumanism and Taoism, I've set up a yahoo group for those wishing to contribute essays to this anthology. If you'd like to contribute, please join the group at:

http://groups.yahoo.com/group/introtranshumanism/

We're also looking for volunteers from transhumanists who don't subscribe to WTA-Talk. It would be much appreciated if those of you who are members of other transhumanist communities could spread the word that we're looking for contributions to this anthology. (Please feel free to forward this e-mail to anyone you think might be interested in contributing--just don't spam anybody, please!.)

If you belong to any of the following groups, for instance, or know people who do, you might want to spread the word to them:

The IEET Fellows
The contributors and editors of JET
The Contributors to the recent ImmInst Book
Speakers at the last two Tranvisions
The Board and Honorary Vice-Chairs of the WTA

Again, thanks for all your efforts on behalf of what I'm sure will be a great book. If you have any further questions, please don't hesitate to contact me directly offlist at pdxwta@yahoo.com.

Tranhumanist individuals and points of view can be found throughout the healthy life extension community and transhumanist groups were amongst some of the earliest modern advocates for life extension technology. Any meaningful introduction to transhumanism should explain and promote healthy life extension - so those of you of a mind to write a submission along those lines should get to it...

UK scientists report on the Asian commitment to stem cell research and regenerative medicine at BioMed Central: "Researchers in China, Singapore, and South Korea are as talented as their UK counterparts. They are probably better funded and equipped. The perspective is more long term in all three countries than the UK ... It was high-quality science. There were clearly centers of excellence, particularly for somatic cell nuclear replacement. ... Overall, the group found that the governments in the three countries were making large amounts of money available for the research and establishing solid infrastructure ... scientists we spoke to have thought long and hard about what products are likely to come to the clinic first and the reasons why."

Link: http://www.biomedcentral.com/news/20050125/01/

Truly revolutionary cancer research is taking place; we have reached the point in capabilities and understanding that allows rapid, amazing progress. Here, EurekAlert reports in progress in the basics of gene therapy using viral vectors: "When added to a mix of normal and prostrate cancer cells, the virus entered both but only produced the toxic protein inside the cancer cells. All the prostrate cancer cells died while the normal cells were unaffected. ... What's exciting is we may now be able to design a therapy that will seek out and destroy only cancer cells ... We hope it will be particularly powerful in eradicating metastases that we can't see and that can't be eliminated by surgery or radiation. Gene therapy, especially for cancer, is really starting to make a comeback."

Link: http://www.eurekalert.org/pub_releases/2005-01/cuco-crl012505.php

I spend a fair amount of time building infrastructure to persuade people to do more than simply make use of the best of present day techniques to stay healthy and extend healthy life span - and I spend less time than I should actually engaged in the process of persuasion. Still, advocacy, activism and supporting the rapid advance of medical science are very important. April Smith's latest post looks at why, in the context of calorie restriction (a present day technique) and the M Prize (an effort to promote the development of better longevity medicine):

For those of us who already invest a substantial amount of our time and energy into the only known way to slow aging down, it only makes sense that we invest some amount of our money into a prize that can motivate scientists and the public at large to focus on finding a real solution, one that does not just hold off the inevitable for a few years, but that repairs the damage so that we can keep on going, just like the Energizer Bunny fresh from a battery change.

In other words, don't focus so much on present health that you fail to invest in future health; supporting medical research is the most effective way to invest in future health. We only have the one chance to do something right now - when it will make the most difference to the future of healthy life extension medicine.

I am rather puzzled by the sudden rush of media attention regarding "contaminated" embryonic stem cell lines.

The human embryonic stem cells available for research are contaminated with nonhuman molecules from the culture medium used to grow the cells, researchers report. The nonhuman cell-surface sialic acid can compromise the potential uses of the stem cells in humans, say scientists at the University of California, San Diego. Their study was published Sunday in the online edition of Nature Medicine.

It's been known for some time that the lines qualifying for US Federal funding were essentially useless for serious science - for this and other reasons. Several better methodologies for developing uncontaminated lines have been developed. I'm not sure that this latest study is saying anything new, despite all the attention.

A number of other lines, such as those developed by Douglas Melton, are available for private or state-funded research - a good thing too, since a large number of lines are needed to get anywhere.

(From the Spiegel Online). William Safire demonstrates that being conservative is no obstacle to seizing on the chance to live a longer, healthier life. The younger conservative voices opposed to healthy life extension technology should have a good long think about how they'll really feel at Safire's age. "With cures for cancer, heart disease and stroke on the way, with genetic engineering, stem cell regeneration and organ transplants a certainty, the boomer generation will be averting illness, patching itself up and pushing well past the biblical limits of 'threescore and ten.' ... Medical and genetic science will surely stretch our life spans. Neuroscience will just as certainly make possible the mental agility of the aging. Nobody should fail to capitalize on the physical and mental gifts to come."

Link: http://service.spiegel.de/cache/international/0,1518,338356,00.html

One of the keys to employing embryonic stem cells in biotech research or regenerative therapies lies in understanding and controlling the way in which these cells differentiate to form different tissue types. Work is proceeding: "When we talked to our colleagues, it was clear that, whether it's cells in the liver, brain, or heart, there had been no practical way for researchers to find the optimal extracellular matrix needed to turn embryonic stem cells into cells with therapeutic potential. We think we've developed an enabling technology for stem cell research and other areas of cell biology in the sense that all of a sudden scientists can use inexpensive and widely available reagents and machinery to optimize the conditions needed to optimize embryonic stem cell differentiation."

Link: http://www.jacobsschool.ucsd.edu/news_events/release.sfe?id=333

Cancer stem cell research is something that we should be watching with interest, if only because an immense amount of money and time is now devoted to the broader field of stem cell medicine. New research into cancer therapies that overlap with the science behind regenerative medicine is likely to move fast over the next decade. As I'm sure we're all aware, curing cancer is high on the list of things we need to accomplish on the way to radical life extension. The forseeable technologies of regenerative medicine will, on their own, only allow you long enough to certainly die from cancer - unless we do something about it.

A recent New Scientist article mentions some aggressive goals for this sort of work:

Cancer treatments could improve by targeting cancer "stem cells" which give birth to all other cells in tumours.

...

Now, new techniques to do this developed at the University of Cambridge, UK, and Kumamoto University, Japan, have been licensed for commercialisation to Stemline, a biotechnology company in New York, US.

"Once we have eradicated the cancer stem cells, in essence we have destroyed the engine responsible for treatment failure and disease recurrence, the major problems for fighting cancer," says Ivan Bergstein, chief executive of Stemline.

But it could be five years before the first treatments start to come through, warns Toru Kondo, head of the team at the University of Cambridge which pioneered the two new tests.

Five years is fast in the world of medical research - this is just another of the many areas in which advancing biotechnology and knowledge is producing real results.

The Telegraph has more on a collaborative public-private funding effort for stem cell research in the UK. This is another example of the spreading ripples from California public funding - all other funding groups and public research organizations have been put in the position of playing catch up. "There is a plan to set up a UK stem cell foundation to encourage and support research into stem cells. The plan is to set up the foundation, get a big chunk of money from the Government and then match that with private money. We started off at the forefront of this science but are now going backwards: nothing is progressing very fast."

Link: http://www.telegraph.co.uk/money/main.jhtml?xml=/money/2005/01/23/cnstem23.xml

The results of research into the aging canine brain have been doing the rounds recently. This ScienceDaily press release highlights the few currently available tools that can modestly slow age-related degeneration in the brain. "Regular physical activity, mental stimulation, and a diet rich in antioxidants can help keep aging canine - and perhaps human - brains in tip-top shape. The [research] is among the first to examine the combined effects of these interventions and suggests that diet and mental exercise may work more effectively in combination than by themselves." Use it or lose it applies just as much to the brain as the body. The future of healthy life extension medicine is promising - but only if you are alive and active to see it.

Link: http://www.sciencedaily.com/releases/2005/01/050121092041.htm

Hype & Hope is one of those "not quite a blog, not quite a news service" offerings that have been springing up of late - many posts and pointers, but little editorializing. Hype & Hope focuses on stem cell research with a more or less equal weight given to financial and business news, noteworthy science and political stories. It looks to be a useful resource in its present incarnation, so hopefully it will stay that way.

Channel NewsAsia reports that a stem cell based cure for diabetes has been successfully trialed in humans by Argentinian researchers. "The 42-year-old man, who had been insulin dependent since the age of 25, so far has seen his glucose levels return to normal with no need for medication. The treatment involves extracting stem cells from the ilium, a bone in the hip, and after manipulating them in the laboratory, injecting them into the pancreas using a special catheter introduced through the femoral artery." First generation adult stem cell therapies that use the patient's own cells have shown great promise in human trials to date - for heart disease also.

Link: http://www.channelnewsasia.com/stories/health/view/128577/1/.html

As BioMed Central puts it, "California's initiative spawns a frenzy in New Jersey, Connecticut, and now New York." This article gives a brief overview of some of the larger public funding initiatives for embryonic stem cell research underway in Eastern US states. "Although Democrats tend to be friendlier to stem cell research and although New York is currently headed by a Republican governor and a Republican majority in the New York Senate, Krueger said she believes the proposals will eventually pass. In the last election, some Republican senators were replaced by Democrats, and the more people hear about stem cell research, the more supportive they become."

Link: http://www.biomedcentral.com/news/20050120/02/

Betterhumans reports on early stage research in mice that suggests the damage caused to neural cells by Alzheimer's amyloid plaques is reversible. "Holtzman suspects that the normal transport of organelles along nerve cell branches breaks down, leading to swellings that have been demonstrated to make it difficult for nerve cell branches to send signals. ... antibodies cleared the plaques and within three days there was also a 20% to 25% reduction in existing swellings." If verified, this provides a ray of hope and more backing for attempts to treat Alzheimer's with vaccines - engineering the immune system into attacking the plaques with antibodies.

Link: http://www.betterhumans.com/News/news.aspx?articleID=2005-01-20-5

A fascinating article at ScienceBlog looks at the work of Christiaan Leeuwenburgh into the biochemical mechanisms of aging in the heart. "We discovered that within the heart [mitochondria], there were large increases of the antioxidant defenses ... When you are younger, those antioxidants act like the supermen of your life to eliminate the free radicals. With age, the free radicals begin to win the battle ... In future studies, we want to look at lifelong calorie restriction and lifelong moderate exercise to prevent the breakdown of the [mitochondria]. The reason we are alive is mitochondria. Discovering how they break down is the first step to understanding the mechanisms of aging."

Link: http://www.scienceblog.com/cms/node/6754

In addition to being the new full time fundraiser for the Methuselah Foundation, April Smith writes very entertaining and thought-provoking posts - in this case a pop culture account of the road that lead her into an interest in calorie restriction, healthy life extension and her current career move:

Since I've decided to take on this new challenge, I've gotten a lot of questions about "Why would you want to live longer?" "Aging is something that happens to all of us, why fight it?" "Isn't it selfish to want to cure aging?"

If you are wondering any of those things right now, I want you to try this experiment. Don't think about aging as it is happening to you: instead, picture the person you love most in the whole world. Then imagine that person getting older... not just getting a few gray hairs and needing reading glasses, but having to hold onto things to walk, afraid of going out for fear of falling on the ice and breaking a hip, perhaps even losing the sharpness of mind that drew you to him or her in the first place, perhaps unable to remember who you are. Being eaten alive by cancer cells, or barely holding onto life in an ICU somewhere, attached to feeding tubes and breathing machines and almost wanting to die but hanging on because life if just too precious to let it go, even in the midst of great pain.

Why is that inevitable? Why let that happen if you have a choice? Why would you accept that suffering, not for yourself but for someone you love, if there's anything, anything at all, that you could do to stop it?

We do, of course, have a chance and a choice - which makes us far luckier than most of the people who have ever lived. The technologies of radical life extension are, figuratively speaking, right around the corner. All that is missing is the funding, the widespread support, the declarations of intent. Just as happened for cancer, Alzheimer's, AIDS research and other worthy causes, this is a a time in which activism and education can make a real and vital difference to the future of medicine and length of our lives.

This has the look of science we'll be hearing more of later: "The spleen might be a source of adult stem cells that could regenerate the insulin-producing islets of the pancreas. ... the same team now report that these potential adult stem cells produce a protein previously believed to be present only during the embryonic development of mammals. ... There may be a previously undiscovered pocket of primitive stem cells in the spleen that are important for healing several types of damage or injury." You might recall that researchers have also identified primitive or embryonic stem cells hiding in adult hair follicles. There may be more such cells to be found elsewhere as well - searching certainly seems to be a worthwhile activity.

Link: http://www.massgeneral.org/news/releases/011905faustman.html

The Telegraph looks at the attempts of bioethicists to divert the course of medical research into regenerative medicine based on embryonic stem cells. As Robert Lanza of Advanced Cell Technology notes, it is "a sad day when we have to use cloning and genetic manipulation to deliberately create crippled human embryos – and not for any scientific reason, but simply to appease religious leaders. I sometimes have to pinch myself to make sure we're not still in the 12th century." Meanwhile, more than 100,000 people continue to die from age-related conditions each and every day - the ethical path here is quite clear: full steam ahead to try and cure age-related conditions and ultimately the aging process itself.

Link: http://www.telegraph.co.uk/connected/main.jhtml?xml=/connected/2005/01/19/ecfstem19.xml

Healthy life extension defies nature - that is an argument you will hear a great deal of if you make a point of advocating longer, healthier lives. (Alongside the Tithonus Error and poorly considered complaints about boredom). By that criteria, however, houses, heating, medicine and all the other trappings of modern society also defy nature - they are very unnatural indeed. Alternatively, one could view them as the natural result of the natural human inclination to effect change in the world. So something deeper is at work here; the charge of defying nature is applied very selectively. Why? Russell Blackford's latest column at Betterhumans is the first part in an examination of "The Supposed Sin of Defying Nature":

Appeals to what is "natural" have a long history in policy debates about unpopular practices - such as homosexual acts, technological innovations and, particularly in recent times, manipulating DNA. The assumption is that there is something wrong morally about interfering with nature's processes, or defying nature itself - however, exactly, those ideas are to be understood.

You'd think that any concept of the inviolability of nature would long have been abandoned by philosophers, ethicists and cultural commentators. But sadly it isn't so. Nature's inviolability is still a club to bash any controversial practice or technology that conservative thinkers dislike.

John Stuart Mill's essay On Nature seemingly exploded the whole idea more than 100 years ago, but it persists in 21st century policy debates. It's like a vampire with a stake through its heart that refuses to die. Choose any of a vast range of controversial topics, from gay marriage to genetic enhancement and beyond, and you'll find a few thinkers willing to argue that it must be stopped because it defies nature.

And so we're left with two questions: Why does this argument persist? And is there anything that we can do about it?

It is always very rewarding to see the effects of education and activism for healthy life extension in action. When you have a few minutes today, wander through the comments on the last three items about Aubrey de Grey posted to Slashdot:

June 02 2004: Engineering an End to Aging

December 03 2004: Live to be 1000 Years Old?

January 19 2005: Do You Want to Live Forever?

I think you'll see quite a transformation for the better, on the whole. It goes to show that presenting the science of healthy life extension a wider audience is a very worthwhile activity. Widespread support and understanding is the engine that drives funding for medical research - private and public - over the long term.

(From the BBC). Work is proceeding on the adaptation of inkjet printing technology to tissue engineering: "inkjets will be able to 'print out' tailor-made human cells to fit a patient's exact dimensions. Human cells are suspended in a nutrient-rich liquid before being printed out in several thin layers. Project leaders say the method could be used to build an organ in a day." Scientists have not yet demonstrated the ability to create large, complex, three-dimensional tissue structures in this way, but research is continuing. As the article notes, our current abilities are limited in comparison: "Using conventional methods, you are only able to grow tissues which are a few millimetres thick, which is fine for growing artificial skin, but if you wanted to grow cartilage, for instance, it would be impossible."

Link: http://news.bbc.co.uk/2/hi/uk_news/england/manchester/4184627.stm

PharmaLive notes that the new Journal of Nanomedicine, the medical use of nanotechnology, is to launch in March. "Nanomedicine has developed very rapidly in recent years, with promising applications in areas such as recognition of cancer cells, stem cell labeling, and monitoring of DNA damage and repair. We hope this journal will provide a new focal point for efforts to advance this revolutionary technology for maintaining and restoring human health." Maintaining and restoring is the path to healthy life extension - you just have to keep it up for longer. Knowledgeable scientists expect nanomedicine to augment and eventually far exceed regenerative and rejuvenation medicine based on current biotechnology.

Link: http://www.medadnews.com/News/Index.cfm?articleid=204829

You can now read biogerontologist Aubrey de Grey's response to the recent Technology Review profile and less than desirable editorials. "Jason Pontin, Technology Review's Editor-in-Chief, and Brad King, Technology Review's Web editor, have invited me to respond to the trio of articles about me and my work that appear in the February 2005 issue of Technology Review with this online-only piece, in addition to a short 'letter to the editor' from me that will appear in the print edition." I think that it hits all the relevant points, and we can hope that the Technology Review will be more circumspect in the future when reviewing the field of healthy life extension - or indeed any other speculative, changing branch of science.

Link: http://www.technologyreview.com/articles/05/01/wo/wo_degrey0101805.asp

It was only a matter of time before the vanity anti-aging marketplace turned its attention to calorie restriction (CR), given the very impressive recent results from ongoing human studies. So here we go: "Histomorphological changes resulting from intrinsic aging affected some of the studied variables in the rat skin, and these changes were delayed or prevented by CR. Some stimulatory effects, such as increased densities of fibroblasts and capillary profiles and higher values of connective tissue fibers resulting from CR, were also observed. Cutaneous morphological changes due to natural aging in this rat model seem to be modified by physiological or metabolic alterations imposed by CR." In other words, CR slows skin aging - it will be interesting to see how the industry decides to try and sell this.

Link: http://archfaci.ama-assn.org/cgi/content/short/7/1/12

I'm happy to relay the following release from the Methuselah Foundation:

On Tuesday, January 18, 2005, Dr. Aubrey de Grey, Chairman of the Methuselah Foundation, announced that recent generous sponsorship donations would enable two people committed to the extension of healthy lifespans to dedicate all of their time and energy toward furthering the mission of the Methuselah Foundation.

"We are at a critical moment in the advance toward new medical therapies that will dramatically extend our youth, health, and longevity," said de Grey. "I'm delighted that several sponsors have recognized the value of the Methuselah Foundation's work as a catalyst for the development of these technologies, and are willing to fund focused efforts in support of the Foundation."

Michael Rae of Calgary, Alberta, will assist Dr. de Grey in research and writing. April Smith of Philadelphia, Pennsylvania will focus on mobilizing funds for the M Prize.

For a list of Expense Contributors go here: www.mprize.org/index.php?pagename=expense_contributors

You might know April Smith from her calorie restriction blog: she also happens to be a professional fundraiser with a long history of experience in that field. Michael Rae is well known in the healthy life extension community and has his fingers in many pies - you should certainly read his excellent essay on The Three Hundred over at the Longevity Meme.

Here is another brace of scientific abstracts from sci.life-extension for your reading pleasure, courtesy of Doug Skrecky. Of especial interest is this item:

Cellular DNA is under constant challenge by exogenous and endogenous genotoxic stress, which results in both transient and accumulated DNA damage and genomic instability. All cells are equipped with DNA damage response pathways that trigger DNA repair, cell cycle arrest, and, if need be, apoptosis, to eliminate DNA damage or damaged cells. The consequences of these processes for stem cells can be profound: diminution in stem cell pools, or, because of altered gene expression, an increased chance for stem cell differentiation or malignant transformation. Furthermore, a number of DNA repair abnormalities are linked to premature aging syndromes, and these are associated with defects in the stem cell population. The specific DNA repair systems for which there are data regarding the impact of repair defects on stem cell function include O6-alkylguanine DNA alkyltransferase, nucleotide excision repair, base excision repair, mismatch repair, non-homologous DNA end-joining Fanconi's anemia protein complex, and homologous recombination. It has recently become clear that deficiencies of these processes are associated not only with cancer and/or aging but also with stem cell defects. This discovery raises the possibility of a link between aging and stem cell dysfunction. In this review, we provide evidence for a link between DNA repair systems and the maintenance and longevity of stem cells.

Some of the most interesting work on stem cells at the moment is unrelated to regenerative medicine - a lot of people would be very happy to see that the degenerative effects of aging are strongly dependent on changes in a small population of cells; e.g. reduced ability of stem cells to repair damage in the body. We don't know whether this is the case or not, but if so it would open the door to another potential class of therapies to slow the aging process. More research is needed, as always!

Sci-Tech Today reports on results from deCode Genetics, the company working on extracting useful information from Icelandic genes: "DeCode scientists have located two sites on Icelanders' genomes where there is some genetic variant that promotes longer life span. ... It occurs at much higher frequency in women over 95 and in men over 90 than in the normal population. ... It is particularly surprising that the same genetic element should promote fertility and longevity since most organisms are obliged to follow a strategy either of breeding fast during short lives or of living longer and having fewer children. ... Usually people think of there being a trade-off between fertility and longevity. So we are getting a free lunch here."

Link: http://www.sci-tech-today.com/story.xhtml?story_id=29778

The New York Times reports on the progress of an initiative to allocate $1 billion in public funds to stem cell research over the next 10 years in New York state. "The proposal, offered by David A. Paterson, the Senate Democratic leader, calls for the creation of a New York stem cell institute to regulate research in the field, as well as make loans and grants to organizations and companies. It is similar to an initiative under way in California, which approved a $3 billion stem cell research fund last year, and to a $380 million proposal announced last week by New Jersey's acting governor, Richard J. Codey." It seems likely that this would have to go to a voter referendum, as for Proposition 71 in California.

Link: http://www.nytimes.com/2005/01/17/nyregion/17stem.html

The offensive editorials and bioconservative tone of a recent MIT Technology Review feature on Aubrey de Grey have attracted a fair amount of attention in the healthy life extension community. While all publicity is ultimately good publicity, I think that we should expect publications like the Review to refrain from ad hominem attacks and other unseemly journalistic offenses. Jason Pontin, the editor-in-chief, has responded to the many comments, noting that the Review will invite Aubrey de Grey to respond to the article - I leave it up to the reader to judge the rest of Pontin's response regarding the personal attacks on Aubrey de Grey.

Link: http://transhumanism.org/index.php/WTA/more/bostrom-responds-to-techrev-attacks-on-aubrey-de-grey-tr-editor-responds-to/

The Times Online reports on the work of a Chinese researcher using live neural tissue obtained while treating accident victims, such as "a patient who had been stabbed in the eye with a chopstick. When the stick was removed it was covered in brain material, which Zhu was able to grow in a culture medium. ... Two months later he had grown several million cells that he transplanted into a patient with a serious head injury. ... The report, written by Minger on Zhu's behalf, said subsequent brain scans showed the cells had grown further and integrated with the patient's surviving brain cells to help them recover abilities lost through the injury." Now the technique is known, researchers must establish a better source of living neural cells - perhaps through culturing of a patient's own cells.

Link: http://www.timesonline.co.uk/article/0,,2087-1442445,00.html

Kudos to Kevin Perrott for his hard work in Edmonton, Canada in connection with Aubrey de Grey's forthcoming talks on the future of real anti-aging medicine. A very busy Kevin notes:

I'm not as optimistic that I made a great live interview with Global Television as they pushed the TV interview I did yesterday to tomorrow or tuesday although I've been assured that there was plenty to work with.. Word to the wise.. if you've had three cups of coffee before noon.. say no to impromptu live interviews at 11:00 AM.. we'll see.. I've been asked to be able to provide an interview a little closer to the date of the talk by another television station... CFRN.

You can see some of the publicity results to date in an Edmonton Sun article and two PDFs of an Edmonton Journal article: Front page and full article. Good job!

News-Medical.Net reports that "researchers have discovered that deletion of a specific gene permits the proliferation of new hair cells in the cochlea of the inner ear -- a finding that offers promise for treatment of age-related hearing loss." General advances in capabilities of research are allowing all sorts of potential therapies and cures for specific degenerative effects of aging to appear on the horizon. This can only be a good thing. "A major obstacle to hair-cell research has been that, since there are not very many hair cells in the inner ear, it has been hard to get enough material for study. But with Zheng-Yi's work, we now have the potential for generating cultured lines of hair cells for experiments."

Link: http://www.news-medical.net/?id=7299

Okinawan longevity and low incidence of age-related disease has been the subject of study for some time now. This article from the Maui News summarizes the conclusions to date; in essence, Okinawan tradition "really resulted in a distinct cuisine that had very high antioxidant loads and very few calories. They ended up being lean all their lives. ... Coupled with physical activity, farming, fishing, you had the right recipe for longevity." So there you have it in a nutshell - calorie restriction, good supplementation, avoidance of excess body fat and moderate exercise. All of these lifestyle choices are readily available for those of us who want to try and make the best of our natural longevity. Why risk missing out on the real anti-aging medicine of the future?

Link: http://www.mauinews.com/story.aspx?id=4999

You'll find an excellent long article at RedNova on the way in which exercise relates to metabolism, gene expression, chronic disease, mitochondrial function, biochemistry, health and longevity. Very good stuff.

To emphasize just how profound this effect is and how recently it has become critical, consider that a century ago type-2 diabetes was never seen in humans younger than 40 years. Even two decades ago it was routinely called "adult-onset diabetes." Today, physicians are seeing "adult" diabetes in 10-year-olds. But it's not just diabetes that's cropping up in youth. Sixty percent of overweight teenagers already have at least one risk factor for coronary artery disease. Whatever merits youth sports may have for social development, young people (and old) need physical activity outside of sports just to maintain metabolic homeostasis to prevent many chronic diseases that will shorten their lives.

...

Work to understand how physical inactivity changes the mixture of proteins made as old skeletal muscle becomes physically inactive remains ongoing. Booth and Scott Pattison of the University of Missouri used small glass plates containing thousands of copies of genes to measure mRNA made by muscle. We found that more than 700 genes (out of about 24,000 measured) changed when comparing old to young skeletal muscles. Since many patients with, for example, broken hips successfully survive the surgical repair but later die with weak skeletal muscles, we wanted to identify the genes responsible for the inability of the weak skeletal muscles to get strong again in old humans. Old rats experience a similar loss in ability to enlarge skeletal muscle after limb immobilization, so we looked at differences using the animal model. A total of 354 genes differed in their expression in skeletal muscle between young and old rats with immobilized limbs. As we write, our current work focuses on determining which of these genes are the culprits that prevent recovery of skeletal-muscle strength after limb immobilization.

By now we hope you'll agree that skeletal muscle is a fascinating and largely underrated tissue. But a richer scientific understanding of its function may also require some changes in the linguistic world. The profound effects of underutilizing skeletal muscle suggest that the old adage "use it or lose it" turns out to be a gross understatement.

Use it or lose it indeed - moderate exercise is continually demonstrated to be one of the four most important things you can do right now for your long term health and longevity. (The other three being a good calorie restriction diet, supplementation and supporting research into real anti-aging medicine).

A short article reprinted at InfoAging reports on the race to deploy adult stem cell therapies for heart disease. "Once a mere fantasy, the idea of growing new, healthy heart tissue to replace damaged or diseased heart muscle is inching closer to reality. ... One approach uses adult stem cells found in bone marrow or the bloodstream. Injected or infused into damaged heart tissue, these stem cells can take up residence and grow into healthy heart muscle. An alternative is to use immature muscle cells taken from the thigh; when injected into the heart, they adopt the characteristics of heart cells. ... a particularly innovative self-repair strategy involves coaxing some heart cells to regress to a stem-cell-like state and then stimulating them to produce young, healthy heart cells."

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

Russell Blackford is one of the few philosopher bioethicists I have time for - in a way it's rather sad that talented people of good sense stand out as exceptions in this field. In a piece at the new Institute for Ethics and Emerging Technologies, he argues that the fight to cure aging is really just a narrow way of looking at a war on ontological diminution:

The idea of a "war on ... er ... ontological diminution" does not sound as resonant as a "war on death" itself, but it may be more to the point in current debates about the prospect of life extension. I have borrowed the phrase "ontological diminution" from Carl Elliott's book Better than Well, where Elliott attributes it to David Gems (apparently in conversation).

Elliott describes the problem as "a flattening of the conditions that sustain our existence" as we grow older. As he puts it, "our senses dim, our minds get slower, our sexual desire diminishes, and our bodies lose their physical capacities."

...

I've come to believe that those of us who favour life extension technology should be more modest in our claims and campaigns. We should not be emphasising the benefits of immortality so much as those of simply living longer, better, healthier (all comparative words) lives.

His view makes an interesting counterpoint to my thoughts on the necessity for a suitable outrageous extreme.

(From Nature). One of the big advantages of the rapid decline in the cost of biotech research is that it makes fishing expeditions an economic proposition: "Researchers have long been trying to find drugs or elixirs that can stave off ageing. But they have met with little success, partly because it is laborious and time-consuming to show that a drug adds years to our lives. To get around this problem, Kerry Kornfeld of Washington University in St Louis, Missouri, and his team tested drugs on a tiny, short-lived worm ... 'We went through a pharmaceutical textbook and picked a drug from each class.'" The end result is new longevity science to investigate - an epilepsy drug that lengthens worm life span by up to 50%.

Link: http://www.nature.com/news/2005/050110/full/050110-16.html

It has to be said that I've lost a fair amount of respect for the MIT Technology Review after their recent article and editorial (or two) on Aubrey de Grey and his work. It's one thing to be opposed to healthy life extension on principle - the author of the rather good Popular Science piece on Aubrey de Grey fell into that category - it's quite another to be running off into the blue yonder with ad hominem attacks and unsubstantiated assertions about the science in question. I think that Damien Broderick, author of The Spike and one of the more entertaining folks on the Extropy list says it all better than I can:

This statement is typical yet strange:

I should declare here that I have no desire to live beyond the life span that nature has granted to our species. For reasons that are pragmatic, scientific, demographic, economic, political, social, emotional, and secularly spiritual, I am committed to the notion that both individual fulfillment and the ecological balance of life on this planet are best served by dying when our inherent biology decrees that we do. I am equally committed to making that age as close to our biologically probable maximum of approximately 120 years as modern biomedicine can achieve, and also to efforts at decreasing and compressing the years of morbidity and disabilities now attendant on extreme old age. But I cannot imagine that the consequences of doing a single thing beyond these efforts will be anything but baleful, not only for each of us as an individual, but for every other living creature in our world.

'When our inherent biology decrees'. But pragmatically 'our inherent biology' seemed perfectly content for almost every human in history and prehistory to perish at about half that maximum, if not very much sooner. I deplore this sad hankering after an essentialist 'decree' that allows doctors like Nuland to squeeze the last drop out of what is in nature wildly '*un*natural' while clinging to some masked version of authoritative or 'sacred' prohibition.

Nuland's essay is notable as well for its whiny and reiterated complaints about Aubrey's intelligence and energy. (What a nerve! Being smart! Being confident! Being articulate!) I expect to see this sort of complaint in Halfwits Review, not Technology Review.

...

But wait, there's more:

But what struck me is that he is a troll. For all de Grey's vaulting ambitions, what Sherwin Nuland saw from the outside was pathetically circumscribed. In his waking life, de Grey is the computer support to a research team; he dresses like a shabby graduate student and affects Rip Van Winkle's beard; he has no children; he has few interests outside the science of biogerontology; he drinks too much beer. Although he is only 41, the signs of decay are strongly marked on his face.

My god! Aubrey doesn't wear a suit! He's (by implication) a drunk! He works with computers! Aging destroys your boyish looks! (Oh wait, isn't that one of the reasons for wishing not to suffer the effects of aging? Oh wait once more, didn't Nuland just write that 'he is a boyishly handsome man'?)

...

And this is such a penetrating sentence:

What does Nuland think of the bearded de Grey's offer of immortality?

A beard! That surely shows what nonsense his claims must be!

...

What's truly extraordinary is that while Dr. Nuland ends by asserting "It is a good thing that his grand design will almost certainly not succeed. Were it otherwise, he would surely destroy us in attempting to preserve us", he makes no attempt at all to show why this might be so, let alone must be.

All we get is smarmy handwaving and loaded language:

"biogerontologists who study caloric restriction in mice and promise us the extension by 20 percent of a peculiarly nourished existence;"

(i.e. not eating like glutted swine on fats and sugars until we expire from our self-inflicted obesity)

"if we are to accept de Grey's first principle, that the desire to live forever trumps every other factor in human decision-making, then self-interest--or what some might call narcissism--will win out in the end."

'Narcissism', for what it's worth, is the psychiatric label for basing your self-estimate on the way other people regard you (as Narcissus fell in love with what he took to be the face of another gazing back at him in a mirrored pond). Yet de Grey as portrayed in the article, and in the disgraceful editorials, is quite immune to that kind of socially imposed self-evaluation. How interesting and self-lacerating this error is.

But in any case, does the desire to live a maximal healthy life trump *every* other factor? I doubt that Aubrey, or most of those in this forum, would make that claim. The curious thing is that at the basis of the scornful attitudes deployed in those editorials and the essay itself is a conviction that life is 'granted' to us--by some supernatural agency, presumably--and that this *does* trump every other factor: "Aging is the condition on which we are given life," we are instructed. Well, I guess that settles it. No further argument is required. Luckily, because none is offered.

Further excellent commentary on the strange and unseemly nature of this particular article and editorials can be found in the Immortality Institute forums and the MIT Technology Review forum - I encourage you to read the article and editorials and then have your say about the quality of popular science journalism we'd like to see from the Review. If they can mess things up this badly in an area where I'm actually qualified to judge, it really does make them a poor resource for reading in a field I'm not familiar with.

Betterhumans reports on more evidence for calorie restriction (CR) as a way to fight Alzheimer's progression - in mice, at least. "Mice predisposed to develop Alzheimer's are protected by a low-calorie, low-carbohydrate diet, providing more evidence that dietary intervention can help prevent the disease and slow its progression. Reducing caloric intake by 30% eliminated the development of amyloid plaque in the mice, considered a fundamental feature of Alzheimer's disease. ... Studying the calorie-restricted mice, the researchers found that their diet activated pathways that break down amyloid peptides in the brain before they form plaques." Calorie restriction has been shown to have a wide range of health benefits in recent years.

Link: http://www.betterhumans.com/News/news.aspx?articleID=2005-01-12-7

The MIT Technology Review is printing a long article on Aubrey de Grey by a fellow who is adamantly opposed to healthy life extension beyond an arbitrary line drawn in the sand. It's an interesting piece, complete with all the old, disproven anti-life-extension arguments, and clearly illustrates the lengths that some folks go to insulate themselves from the slightest acceptance of longer, healthier lives as a good thing. I have nothing against people who choose not to live a longer life - freedom is vitally important - but the doom and gloom crowd who wish to block medical science and cap all life spans at their arbitrary limit are a real threat. Healthy life spans have greatly increased over the past century and the sky hasn't fallen - nor will it.

Link: http://www.technologyreview.com/articles/05/02/issue/feature_aging.asp?p=0

The bioconservatism discussion over at the Immortality Institute is getting interesting. You should take a look. Aubrey de Grey used this as an opportunity to preview the latest updates to his Strategies for Engineered Negligible Senescence website - a fair amount of new material has been added based on the discussions and experience of the past year.

OK, my site is fully updated. I rushed it a bit for our new friend, so readers are welcome to mail me with bug reports. Oh, and feedback on the text is OK too....

SFGate notes that a South Korean team has been permitted to proceed with therapeutic cloning and embryonic stem cell research: "[the] team of scientists who produced the first cloned human embryo last year were given government approval Wednesday to proceed with stem-cell research to find cures for diabetes, cerebral palsy and Parkinson's and other diseases -- but not for work toward reproductive human cloning ... scientists hope this research will one day allow them to grow replacement tissue to treat spinal cord injuries as well as diabetes and other diseases." That teams outside the US are forging ahead makes it less likely that the US goverment will be able to shut down this very promising research.

Link: http://www.sfgate.com/cgi-bin/article.cgi?file=/news/archive/2005/01/12/financial1028EST0076.DTL

It's always exciting to see genes and proteins you recognize as being important to one area of study showing up in a related field - it implies that researchers are getting closer to a good understanding. Medical News Today reports on a program that "will study how key enzymes are regulated and should increase our understanding of the essential mechanisms governing appetite, food intake and energy consumption. Learning more about how the body responds to exercise at a molecular level will, for example increase our understanding of how the body regulates energy intake in the form of food and appetite control and energy output such as burning off fat and affecting metabolic rate." This overlaps nicely with ongoing studies of calorie restriction and mitochondria as they relate to metabolism and healthy life span.

Link: http://www.medicalnewstoday.com/medicalnews.php?newsid=18788

MSNBC mentions Elixir Pharmaceuticals in an article on up and coming biotech companies. "Elixir Pharmaceuticals Inc. begins 2005 as an early-stage drug development company focused on the science of aging. But the company plans to end the year as a much more mature version of itself, with at least one drug generating revenue and two in clinical trials, thanks to some anticipated licensing deals with larger partners. And assuming those milestones are accomplished, Elixir plans to go even further and pursue an IPO." As you may recall, Elixir has been researching the biochemistry of calorie restriction and longevity genes. Financial success means more companies entering this field - a good thing for all of us in the long run.

Link: http://msnbc.msn.com/id/6806865/

An interesting discussion on bioconservatism and related ideas is currently underway at the Immortality Institute: embryonic stem cell research, transhumanism, human dignity (whatever that might be), healthy life extension and the scientific path towards an ageless future are all up for debate. What do you think about attempts to restrict medical research or the way in which bioethical arguments are conducted in our society? What is the nature of being human and where do we (or should we) draw the line? You should drop by and have your say; the bioconservative side of the conversation is being held up by a smart fellow with a readable writing style.

Link: http://www.imminst.org/forum/index.php?s=&act=ST&f=1&t=5051&st=0

Biogerontologist Aubrey de Grey will be giving a presentation entitled "The Foreseeability of Real Anti-Aging Medicine, a survey of relevant biotechnology and likely timeframes" at the University of Alberta, Canada, on February 15th.

Does anti-aging medicine exist yet? Certainly not in the sense in which the word "medicine" is normally used, i.e. therapies that cure people of the condition from which they are suffering. The therapies that we have today to combat some of the effects of aging are valuable, but a genuine anti-aging medical treatment will be incomparably more valuable, as it will restore elderly people to the physical and mental vitality of their youth -- and keep them youthful thereafter. It is therefore essential to be aware that these more powerful therapies are not nearly so far in the future as one might think. In this talk I will discuss the details of some of the components of a foreseeable panel of true rejuvenation therapies and explain why it is likely that, with the proper commitment and funding, this panel can be implemented in mice in just ten years from now and in humans in only 15-20 years thereafter.

If you are in the vicinity, you should certainly look at attending. Aubrey de Grey is a good, entertaining speaker - I recommend hearing about the Strategies for Engineered Negligible Senescence initiative from the horse's mouth, as it were.

A number of interesting conversations relating to fundraising, activism and support of healthy life extension research are currently underway in the Immortality Institute Action and Reaching Out forum. Take a look and see what folks have in mind for the year ahead: the ongoing growth of the Methuselah Mouse Prize for anti-aging research has made it much more likely that other successful fundraising efforts will emerge in the near future.

The BBC reports on yet another explanation for the well known difference between male and female life spans. "Men's hearts lose up to a quarter of their pumping power from 18 years old to 70. But there was little change in women's hearts from 20 to 70, the study of 250 people said. The researchers said the difference may explain why women live on average up to five years longer than men." The tendency of women to take better care of basic health matters has also been suggested as a root cause, as have trends in smoking. For my part, I think that fewer statistics and more research into regenerative medicine - doing rather than watching - would be a good plan.

Link: http://news.bbc.co.uk/1/hi/health/4161755.stm

(From Medical News Today). The Reliability Theory of aging suggests that we are born with a surprisingly large amount of cellular or genetic damage - or vulnerabilities that lead to the same long term effects as damage. Modern bioinformatics, genetic toolkits and embryonic stem cells allow researchers to investigate how this might happen: "We are trying to identify the primary factors that influence the methylation process and which therefore might affect an unborn child's long-term susceptibility to certain diseases in later life. We can use unspecialised stem cells to study the effect of [maternal] diet on the tagging of the DNA and then induce them to develop into a cell type such a heart cell to see whether the effect is still there."

Link: http://www.medicalnewstoday.com/medicalnews.php?newsid=18739

Limiting available energy through calorie restriction has been shown to extend life span (and provide numerous health benefits) in a variety of species. ScienceDaily notes recent research from Elixir Pharmaceuticals: "Using an array of genetic and molecular tricks on nematode worms, the team demonstrated that animals with extra copies of the AMP-1 enzyme lived on average 13% longer lives than controls. Other experiments demonstrated that environmental stressors that activate the AMP-1 enzyme, also lead to longer lived animals. ... The discovery that a sensor of energy levels regulates lifespan is very exciting because it tells us that the worm is actively making a decision in adjusting its lifespan in response to its energy state." The related biochemistry is very similar in humans, so stay tuned.

Link: http://www.sciencedaily.com/releases/2004/12/041203084728.htm

(From Newsweek). "Are the changes in the brain that accompany aging caused by damage to the underlying genes involved in functions such as learning, memory and the transmission of nerve impulses? Exciting new research suggests that they may be, and the findings could eventually help predict and prevent degenerative brain diseases like Alzheimer's and Parkinson's." The spectrum of possible degenerative conditions in the brain is as wide as the brain is complex - the well known conditions are simply those we see most often. Far greater understanding of brain genetics and cellular biochemistry is absolutely necessary for significant extension of the healthy human life span. What lies beyond cured Alzheimer's in a much longer life? We have no idea yet.

Link: http://msnbc.msn.com/id/6803301/site/newsweek/

A couple more interesting items from sci.life-extension to brighten up your day.

Nuclear DNA may be the key to aging after all:

It has been proposed that somatic mutations make major contributions to aging. The first paper, based on a gene knock-in mouse, supports a contributory role for mutation in [mitochondrial DNA] (mtDNA) in aging, but does not support a damaged-mtDNA-producing-more-damaged-mtDNA hypothesis. The second paper indicates some GC-rich sequences in the nuclear DNA are more sensitive to oxidative damage than mtDNA. As a result, key genes involved in brain function and mitochondrial function are progressively inactivated with age. Failure in these nucleus-encoded mitochondrial genes may be a primary reason for mitochondrial failure in old age.

In other words, these researchers suggest that there is no feedback mechanism associated with ongoing damage in mitochondrial DNA, the cellular powerhouses, and reduction in mitochondrial function with age is caused by changes in cell nucleus DNA.

Cerium oxide nanoparticles extend cell longevity:

Nanobiology implies application of the engineering concepts of nanotechnology to biological systems, providing novel opportunities to intervene in the pathology of disease. Here, we have merged nanoscale engineering with cell biology to intervene in a common biomedical pathology, that being aging and free radical-induced cell dysfunction.

...

We hypothesize that the unique valence structure of cerium oxide, in the nanoparticle form, promotes cell longevity and protects against free radical-mediated injury by acting as a regenerative free radical scavenger.

The search for ever better antioxidants (free radical scavengers) has been going on for quite some time, ever since the free radical theory of aging was first developed. It remains to be seen whether current nanoscale materials science can do significantly better than the antioxidants already sold by the supplement industry.

The Daily Northwestern takes a look at proposals for public funding of an Illinois Regenerative Medicine Institute and the science behind stem cell based regenerative medicine. "Professors conducting stem cell research at Northwestern's Feinberg School of Medicine said they support a state proposal to implement a 6 percent tax on elective cosmetic surgery. If passed, the proposal would fund roughly $100 million a year specifically for stem cell research." The new technology of therapeutic cloning is a focus - it is required to produce stem cell lines for research into the biochemistry and genetics of currently incurable diseases, as well as some of the other promising uses of embryonic stem cells. Therapeutic cloning is still under threat in the US due to pending federal anti-research legislation.

Link: http://www.dailynorthwestern.com/vnews/display.v/ART/2005/01/07/41de474a34dfc

As I mention every now and again, diagnostics is important. Catch any disease very early on - even those that are currently untreatable in late stages - and often something can be done to at the very least delay progression. SFGate reports on a new test for the early diagnosis of Parkinson's disease: "By the time unambiguous symptoms emerge, Parkinson's has usually been on the attack for years, destroying 60 percent or more of the special cells in the brain that control voluntary movement. ... Now scientists at drug giant Pfizer think they have stumbled on a simple test that is both sensitive enough to detect subtle biological changes due to Parkinson's and specific enough to avoid false alarms: analyzing how people speak."

Link: http://www.sfgate.com/cgi-bin/article.cgi?f=/news/archive/2005/01/07/financial0941EST0047.DTL&type=health

The Science Advisory Board hosts a number of science blogs. The latest addition is Longevity Science from Leonid Gavrilov. You may recall his work (with Natalia Gavrilova) on the Reliability Theory of aging, good science that I think we'll be hearing more of in the years ahead. You can find out more about the work of Leonid Gavrilov and Natalia Gavrilova on aging and longevity at their website.

Numerous studies demonstrate that many manifestations of aging can be postponed or even reversed, and that lifespan can be significantly extended in experimental animals. Moreover, our own studies found remarkable plasticity of human longevity ... and suggest that there may be a significant potential for further extension of human lifespan.

A discussion of stem cell research in the Danvers Herald provides a good feel for the reasons why research into the human brain is vital to the future healthy life extension. The more we learn, the more we find can go wrong in the aging brain; articles like this make Paul Allen's decision to fund the Brain Atlas project look very smart. Twenty years from now, when most of the major organs in the body can be repaired in situ or regrown from scratch, regenerative neuroscience will become increasingly important. The brain is in a class of its own - the one organ we can't just replace as a matter of last resort. The technologies used to repair aging or damaged brains must, by necessity, be more advanced.

Link: http://www2.townonline.com/danvers/localRegional/view.bg?articleid=160021

Biomarkers are an important part of the medical diagnostic toolkit. Diagnostics isn't as flashy as the search for a cure, but bear in mind that many age-related conditions could be ameliorated or avoided entirely if predicted or otherwise caught in very early stages. EurekAlert reports on the identification of a biomarker for osteoarthritis: "a chronic degenerative joint disease, osteoarthritis (OA) is a common cause of pain and disability among older Americans. OA of the knee affects up to 6 percent of the older population, while OA of the hip affects about another 3 percent. While treatments vary, there is hope that early intervention - before joint destruction can be clearly seen and measured on an X-ray image - will improve outcomes."

Link: http://www.eurekalert.org/pub_releases/2005-01/jws-abt010705.php

Two articles today provide good examples of the way in which cancer research benefits all fields of medicine. Effectively fighting cancer requires detailed knowledge of biochemical and genetic mechanisms and the ability to manipulate cellular processes - one could argue that all of the effort prior to the 1990s went into developing the tools to make the tools to do the work. Only with comparatively recent capacities in genetics and bioinformatics has real progress been made in understanding cancer and developing cures. This work brings very real benefits to all other areas of medicine - knowing how cells work is revolutionizing the way in which new medicine is created.

Researchers Tease Out One Critical Role Of Tumor-Suppressor Gene

While mutations in Rb, are linked to several types of cancer including the childhood disease retinoblastoma, Rb normally keeps cell division in check. That means Rb is a tumor suppressor gene, which keeps cells from growing out of control. Scientists believe that Rb is linked to two key processes that frequently malfunction when cancer begins - proliferation (cell growth), and apoptosis (cell death).

...

Knowing how Rb functions in normal cells could clue scientists in to the gene's behavior as a tumor suppressor and why it mutates. It could also ultimately help scientists understand how other types of cancer progress.

"Cancer cells are altered in so many different ways that it's hard to conduct controlled experiments with them," Leone said. "That's why we need to figure out what Rb normally does, as opposed to studying a mutated version of the gene in a cancer cell. This may also help us uncover the mechanisms that cause mutations in other tumor-suppressing genes."

Pitt scientists study how cancer cells get out of control

"Virtually all cancer cells acquire the ability to change their genomic structure," said Saunders. "Researchers in the field are looking for single events that can cause multiple mutational changes to the genome, and this research is an example of that."

Before a normal cell divides, its chromosomes are duplicated and then pulled apart by a structure called a spindle, so that the two daughter cells each will have the same number of chromosomes.

At the end of a normal spindle is the spindle pole, also called the centrosome, which pulls the chromosomes outward. Cancer cells often have extra centrosomes. When a cell has more than two centrosomes, sometimes--but not always--the spindles will have more than one pole and cell division won't work correctly, leading to the swapping of genetic material, uncontrolled cell division, and the formation of tumors.

Why this doesn't always happen when there are too many centrosomes was the focus of the Pitt researchers' investigation. They found that as long as the extra centrosomes "cluster" together, the spindles will form normally, with two ends, and the cells will divide normally. "No one else appreciated that that was required, or what the mechanism was that separated them," said Saunders.

...

Investigating the mechanism by which this occurs, the researchers found that in cultured oral cancer cells a protein called dynein is missing from the spindle, and the centrosomes no longer cluster together.

Furthermore, the researchers discovered that in some types of tumors, dynein is inhibited by the overexpression of another protein called NuMA. Excess NuMA seems to prevent dynein from binding to the spindle. When they reduced the level of NuMA in cultured cancer cells, the dynein returned to the spindles, and the spindles were no longer multipolar.

"This finding suggests that a possible treatment for some types of cancer could be a drug that inhibits NuMA."

This sort of detailed knowledge of cellular processes will invariably prove useful to other scientists in other fields of medicine. There is no useless piece of the puzzle when it comes to understanding how our bodies work. Curing cancer is a very necessary part of the march towards longer, healthier lives - but the knowledge acquired while doing it will be essential to more directed attempts to extend the healthy human life span.

Here are two more items relating to ongoing attempts to fund, legalize or ban stem cell research around the US.

In Connecticut:

Following in the footsteps of California and New Jersey as well as other US states, the Connecticut legislature may this year pass legislation allowing both adult and embryonic stem cell research - a bill the state's governor, Jodi Rell (R), has said she will sign.

...

"Last year, all we wanted to do was make sure that Connecticut was a supportive place for research in adult and embryonic stem cell biology," Krause said. "But now that proposition 71 has passed in California and there are funds to recruit stem cell biologists, they are going to be able to start to recruit people away from existing institutions in Connecticut."

In Massachusetts:

Democratic leaders on Beacon Hill vowed yesterday to immediately push legislation to promote stem cell research in the Bay State, hoping to blunt the appeal of California's $3 billion investment in stem cell research.

Looking back, now that various local governments are falling over themselves to fund or otherwise back embryonic stem cell research and regenerative medicine, I think it is a useful exercise to examine just how we came to this point. How did bans, threatened legislation and a lack of public support a few short years ago transform into the situation we see today?

Details aside, I think that it is important to recognize that this didn't "just happen." Given that medical advances have historically been accepted with enthusiasm after initial resistance, there is a tendency towards complacency amongst some supporters of healthy life extension. This is a dangerous attitude! A great deal of time, resources and hard work were necessary to make progress in this case, as for other advances in medicine, from penicillin to IVF technologies. The fight isn't over yet, either - anti-research legislation is still pending at the federal level.

You get the future you are willing to create, which is why activism for medical research is vitally important.

The Financial Express notes public funding initiatives for human embryonic stem cell (ESC) research in India: "He said that at the national level, the scientists, in order to carry out human ESC research activities, have identified six city clusters across India. They are - New Delhi, Bangalore, Pune, Mumbai, Hyderabad and Vellore. These clusters will involve researchers exchanging ideas and carrying out research activities in the field of basic and applied sciences. ... Besides India, stem cell research activity is being carried out in the US, Korea and Japan, and our country remains an active practitioner of human ESC research activities."

Link: http://www.financialexpress.com/fe_full_story.php?content_id=79029

From Express Newsline: "While scientists around the world debate the ethical issues surrounding use of stem cells for medical treatment, India has already taken lead in this direction and has conducted the world's biggest and most successful adult stem cell experiment. ... The LV Prasad Eye Institute has been into adult stem cell research for the last six years and doctors at the hospital have successfully reconstructed over 160 damaged retinas using stem cells." Indian researchers are also working on stem cell based regenerative medicine for heart disease, another currently promising direction. First generation therapies based on transplants and adult stem cells are working well in trials - even though we don't yet know how they work.

Link: http://cities.expressindia.com/fullstory.php?newsid=112962

Life expectancy is an apparently straightforward term that hides a number of subtleties. From Wikipedia:

In demography, life expectancy is a statistical measure of the average, or mathematical expected value, of the remaining lifetime of an individual in the given group. For non-human organisms the term lifespan is often used to indicate the average length of life in a given species.

Notice that the life expectancy is heavily dependent on the criteria used to select the group. In countries with high infant mortality rates, the life expectancy at birth is highly sensitive to the rate of death in the first few years of life. In these cases, another measure such as life expectancy at age 10 can be used to exclude the effects of infant mortality to reveal the effects of other causes of death. Usually, though, life expectancy at birth is specified. To calculate it, it is assumed that current mortality levels remain constant throughout the lives of the hypothetical newborns.

Large reductions in infant mortality are responsible for much of the increase in birth life expectancy over the past century. Other contributions come from the reduction in chronic illness and the resulting damage it causes - all damage to a living being is likely to reduce life span according to the Reliability Theory of aging. As James Vaupel put it recently:

Life expectancy [at birth] is a measure of current conditions. It is not a prediction about how long somebody will live. But it's a measure of how long a person, a baby would live if that baby was confined to this year, could not get out of this year, was stuck with the conditions of this year.

It is slowly occurring to me that many folks, mainstream journalists included, use the term "life expectancy" in a fairly imprecise way. It doesn't mean projected life span, and it's not even all that useful to mention life expectancy unless you carefully qualify the group you are talking about. Life expectancy for who, and under what assumptions? There are plenty of examples of this sort of imprecision and mistaken meaning in the current debate over social security.

An article from Innovations Report goes into some detail on efforts by tissue engineers to grow new skin: "Our goal is to bioengineer an artificial skin scaffold that promotes tissue regeneration and even directs cell growth for hair follicles and sweat glands so that the new skin would look and feel like normal skin. ... Ultimately, we are interested in understanding and finding the right mixture of biological and synthetic materials that will yield the best results for wound healing and tissue regeneration and will significantly increase the quality of life for severe burn victims and medical patients." Like all matters biological, it is much more complex than you might at first imagine.

Link: http://www.innovations-report.de/html/berichte/biowissenschaften_chemie/bericht-38471.html

(From NewsDay.com). The latest proposal for public funding of stem cell research has been floated in New Jersey: "New Jersey would invest $500 million in stem cell research under a proposal acting Gov. Richard J. Codey is expected to unveil next week in his State of the State address. ... Cohen, who favors a $1 billion investment, said legislation to put the initiative on the November ballot could be ready for introduction in three months." The New Jersey initiative is one of the more advanced of a number of similar proposals and debates in other US states. We still need to do away with anti-research legislation at the federal level, however, as this continues to damage private investment in regenerative medicine research.

Link: http://www.newsday.com/news/local/state/ny-bc-nj--statehousebriefs0104jan04,0,6070983.story

Anti-research groups and politicians in Missouri will continue to try and force through a ban on therapeutic cloning (or SCNT) this year. "A statewide ban on SCNT would limit Missouri's ability to recruit and retain biomedical scientists, and not just those who want to work with embryonic stem cells. ... The damage would extend far beyond regenerative medicine to every field of biomedical research ... The more people know about this research procedure and understand its potential to relieve human suffering, the more supportive they become." Therapeutic cloning is an essential technology for the production of stem cell lines used to explore the biochemical mechanisms of disease - the best first step towards a cure.

Link: http://www.biomedcentral.com/news/20050103/01/

A press release I stumbled across today pointed me in the direction of an interesting piece on the scientific definition of a stem cell. You'll have to pass through the gateway page for the Stem Cells and Development journal to read the PDF - click on the link for "Stem Cells: Shibboleths of Development" on that page.

... the Mouse replied rather crossly: "Of course you know what 'it' means."

"I know what 'it' means well enough, when I find a thing," said the Duck. ...

...

As the fields of development and stem cell research have evolved, different concepts have emerged in these two seemingly interrelated disciplines. As a result, developmental scientists view stem cells somewhat differently than clinical scientists, who have successfully used what they characterize as stem cells for therapeutic purposes. These latter pioneers include hematologists, who by demonstrating the reconstitution of an organ system with a single multipotent cell, have an undeniably strong claim to defining the concept of what constitutes the stem cell. Prior to, and, as will become evident, following this dramatic result, hematologists and developmentalists have viewed stem cells very differently; classifying stem cells as any that led to further development and differentiation. Consequently, the vernacular and rhetoric associated with any one journal claiming an interest in stem cell research has promoted only one of these paradigms.

Stem Cells and Development seeks to integrate the wealth of information the two disciplines provide and thereby close, or at least shrink, the gap between the two positions.

This sort of piece will become more common as research runs more rapidly than the process of accepting firm definitions and nomenclature. What is a stem cell? Is all stem cell research in fact using stem cells, or should we be calling some of these cells by a different name? Read the article and see what you think.

Scientists are making real progress in developing therapies for heart damage. Here, EurekAlert reports on a study showing that human cord blood stem cells (HUBC) can repair heart attack damage in rats. "The HUCB stem cells were injected directly into the heart muscle of rats an hour after heart attacks were induced. After four months of recovery, the size of scar tissue left by dead heart muscle was approximately three times smaller in the HUCB treated rats than in the untreated rats. As a result, the heart's pumping capacity improved to near normal in the treated rats, after an initial decline, and was significantly greater than the cardiac function in the untreated rats with heart attacks." As the article notes, scientists are still trying to understand how stem cells work to repair damage in these types of therapies.

Link: http://www.eurekalert.org/pub_releases/2005-01/uosf-sct010405.php

Scientists reported successful treatment of the rat version of Parkinson's disease using embryonic stem cells back in April of this year.

The Israeli team treated human stem cells in the laboratory. They then transplanted them into the brains of rats which had a Parkinson's-like condition. The rats' behaviour changed after their treatment. Before it took place, they would turn continually, and would be unable to make side steps while they were being dragged across a surface. But after the transplants, these symptoms were significantly reduced. When post-mortem examinations were carried out on the rats, it was found that the stem cells had developed into dopamine-producing cells.

Betterhumans noted today that similar work now has been accomplished in monkeys:

Takahashi and colleagues had previously shown that mouse embryonic stem cells can differentiate into neurons when cultured under specific conditions. The same culture approach - considered technically simple and efficient - was also recently shown to work in primate embryonic stem cells.

For the new study, Takahashi and colleagues generated neurons from monkey embryonic stem cells and exposed them to a growth factor called FGF20. The growth factor is produced exclusively in the part of the brain affected by Parkinson's disease and is reported to help protect dopamine-producing neurons.

The growth factor increased the development of dopamine-producing neurons, which the researchers then transplanted into monkeys with a primate model of Parkinson's disease. They found that the transplanted cells functioned as dopamine-producing neurons and lessened Parkinson's symptoms.

A few years ago, many observers - myself included - suspected that Parkinson's treatments would be one of the first widely available first generation regenerative therapies based on stem cells. That may still be the case, unless therapies for paralysis and heart disease arrive first. It is interesting to note that the varied therapies attracting the most attention and funding at the moment are all quite different in their approach and utilization of stem cells. This is a very positive sign.

(From EurekAlert). Scientists have made more progress in understanding the mechanisms of cell aging. "Aging cells are called senescent cells [and are] no longer able to divide but remain metabolically active. Accumulation of senescent cells over time appears to contribute to changes in tissue form and function commonly associated with aging, like the skin changes that occur between childhood and old age. ... Most importantly, the failure of cells to stop growing through differentiation or senescence can lead to the uncontrolled growth of cancer." This work identifies more of the biochemical mechanisms that control senescence; further investigation "might allow rationale design of therapeutics to treat cancer patients and even alleviate some aspects of human aging."

Link: http://www.eurekalert.org/pub_releases/2005-01/fccc-fcc123004.php

ScienceDaily reports on a new study that sheds more light on the way in which stem cells work to regenerate damaged heart tissue. "Most of all, this study is important because it begins to explain why stem cells can help a heart heal. Clinical trials that use bone marrow [adult] stem cells in people with heart damage have shown promise, but no one knows how it works. This starts to provide an explanation. ... human stem cells use different methods to morph into two kinds of cells needed to restore heart function - cardiac muscle cells that contract the heart as well as the endothelial cells that line blood vessels found throughout the organ."

Link: http://www.sciencedaily.com/releases/2004/12/041219183402.htm

ScienceDaily provides a wonderful example of the way in which our increased ability to work with genetic information has revolutionized the process of developing therapies. Researchers can now identify the precise biochemical mechanisms behind a given disease - and then try to tailor a drug or therapy to precisely manipulate or block that mechanism. This is a huge step forward over the old ways and greatly speeds the advance of medicine. "Researchers have known that mutations in a key gene called parkin are a major cause of Parkinson's disease (PD). Now they have discovered a new mechanism by which the parkin gene can be compromised, a finding that they say could lead to new drugs for the disorder."

Link: http://www.sciencedaily.com/releases/2004/12/041219195508.htm

Even in the age of biotechnology, you must take care of the basics if you want to live healthily for long enough to benefit from future advances in medicine and longevity. InfoAging provides another reminder of the importance of regular exercise to health: "[Exercise] helped reduce metabolic syndrome - the potentially deadly mix of risk factors that can make a person more likely to develop heart disease, diabetes or stroke. These risk factors include high blood pressure, excess fat around the abdomen, elevated blood sugar levels and abnormal cholesterol levels. ... At the start of the study 43% of the participants had metabolic syndrome. After the six-month programme, those in the exercising group saw no new cases of the syndrome and the condition had been resolved in nine people - a reduction of 41%."

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

ScienceDirect provides free access to the contents of the latest issue of Aging Research Reviews. Have a look through; it's a good way to gain an impression of the state of aging research today.

As the average human life expectancy has increased, so too has the impact of ageing and age-related disease on ou society. Ageing research is now the focus of thousands of laboratories that include leaders in the areas of genetics, molecular and cellular biology, biochemistry, and behaviour. Ageing Research Reviews (ARR) covers the trends in this field. It is designed to fill a large void, namely, a source for critical reviews and viewpoints on emerging findings on mechanisms of ageing and age-related disease. Rapid advances in understanding of mechanisms that control cellular proliferation, differentiation and survival are leading to new insight into the regulation of ageing. From telomerase to stem cells to energy and oxyradical metabolism, this is an exciting new era in the multidisciplinary field of ageing research. The cellular and molecular underpinnings of manipulations that extend lifespan, such as caloric restriction, are being identified and novel approaches for preventing age-related diseases are being developed. ARR publishes articles on focussed topics selected from the broad field of ageing research, with an emphasis on cellular and molecular mechanisms of the aging process and age-related diseases such as cancer, cardiovascular disease, diabetes and neurodegenerative disorders. Applications of basic ageing research to lifespan extension and disease prevention are also covered in this journal.

In particular, you might find "Lessons learned from gene expression profile studies of aging and caloric restriction" to be an interesting paper. Joao de Magalhaes also has a paper in the latest issue, entitled "Open-minded scepticism: inferring the causal mechanisms of human ageing from genetic perturbations":

Given the myriad of age-related changes and the many proposed mechanistic theories of ageing, a major problem in gerontology is distinguishing causes from effects. This review aims to identify and evaluate those mechanisms which have gathered experimental support in favour of seeing them as a cause rather than an effect of ageing. Recent results related to energy metabolism and ageing, the free radical and the DNA damage theories of ageing are reviewed and their predictions evaluated through a systems biology rationale. Crucial in this approach are genetic manipulations in animal models that enable researchers to discriminate causes from effects of ageing and focus on the causal structure of human ageing. Based on a system-level interpretation, the GH/IGF-1 axis appears the most likely explanation for caloric restriction and a possible causal mechanism of human ageing. Although much work remains to fully understand the human ageing process, there is little evidence that free radicals are a causal factor in mammalian ageing, though they may be involved in signalling pathways related to ageing. On the other hand, studying how the DNA machinery affects ageing appears a promising avenue for disclosing the human ageing process.

"To lengthen thy life, lessen thy meals." Starting with those wise words from Benjamin Franklin in 1733, ScienCentral takes a look at the mechanisms of calorie restriction (CR). "Can we find other ways of creating this same state as calorie restriction creates without having to calorie restrict? ... CR appears to trigger a gene called Sir (Silent Information Regulator) 2, which seems to be directly linked to prolonging lifespan in different organisms. ... Our studies show that, in fact, when you increase Sir2, you live longer; when you block Sir2 from being able to be increased, you can block the calorie restriction response ... What we're trying to achieve is a longer lifespan while maintaining our healthy physiology longer."

Link: http://www.sciencentral.com/articles/view.php3?type=article&article_id=218392437

Most important improvements in medicine don't get all that much press. It's improvements in the glue that holds the system together - and the resulting reduction in cost of medical processes - that will make as much difference in the future of your health as more flashy prospective developments, like cures for cancer and working anti-aging therapies. Infrastructure is only boring and unromantic until you start to consider what might be possible if you cut specific costs by a factor of ten, or a hundred, or a thousand - let's say the costs of obtaining, moving and processing medical data, for example:

Meeting the needs of those with the chronic diseases of aging - heart disease, Alzheimer's, and so forth - is a labor-intensive chore we increasingly cannot afford. Health care consumes 15 percent of the U.S. gross national product, up from 5 percent in 1960. In Japan and Europe, which manage care more frugally, the share has in most cases already passed the 10 percent mark. And the numbers continue to rise. We will have to find clever ways to economize on labor, the most expensive element in health care. "General practitioners and other front-line health care people are overwhelmed; they haven't got time for patients, and the vast majority would welcome relief from some well-chosen, well-placed technology," says Philippe M. Fauchet, an electrical engineer and director of the Center for Future Health at the University of Rochester, in New York. He and others are betting that information gleaned from our increasingly networked world will be a big part of the solution.

As the folks at FasterCures correctly identified, working on the infrastructure that could make costs of new medicine fall more rapidly is a desirable goal. Medicine is increasingly becoming an information industry; this means that the major costs and trends could all be subject to the same level and scale of improvements that bioinformatics has brought to medical research. If, that is, that regulatory and other monopoly obstacles can be overcome. Medicine is a backward and inefficient industry precisely because enormous costs are imposed on improvement and innovation by government at the behest of medical associations and other protectionist groups.

John Schloendorn is undertaking an online survey of attitudes, opinions and background in connection with Aubrey de Grey's proposed Institute of Biomedical Gerontology (IBG). This has some similarities to the marketing surveys employed by large advertisers; the results will be used to guide fundraising strategies for the Methuselah Foundation and the future Institute of Biomedical Gerontology. The survey runs through to the end of January, so please do take a few minutes to help enable more effective fundraising for serious anti-aging research. Related discussions are taking place at the Immortality Institute, so drop by and have your say.

Link: http://www.pvexperiment.bravehost.com/IBGS/