$36,000
$24,120

Don't Expect Science to Save You From Negligence

I think that an important point is illustrated in a recent study on the relative cost and effectiveness of a good lifestyle versus drugs on age-related diabetes.

Compared with the placebo intervention, the lifestyle and metformin interventions were estimated to delay the development of type 2 diabetes by 11 and 3 years, respectively, and to reduce the absolute incidence of diabetes by 20% and 8%, respectively. The cumulative incidence of microvascular, neuropathic, and cardiovascular complications were reduced and survival was improved by 0.5 and 0.2 years. Compared with the placebo intervention, the cost per [quality-adjusted life-year (QALY)] was approximately $1100 for the lifestyle intervention and $31,300 for the metformin intervention. From a societal perspective, the interventions cost approximately $8800 and $29,900 per QALY, respectively. From both perspectives, the lifestyle intervention dominated the metformin intervention.

In other words, if you're not taking good care of yourself now, don't expect your future medical bills to be low. Even though the cost of medicine of a given effectiveness should decline with time - due to competition in the markeplace, increasing research into efficiency and effectiveness, improval of existing methodologies, and so forth - this trend could quite easily be offset by encroaching socialism in medicine.

Besides paying some of the highest prices for health care, we have the dubious distinction of having the most heavily regulated healthcare system in the world. In no other country on earth are doctors and hospitals subjected to as many oversight and enforcement agencies, bureaus and commissions. Rules, regulations, and laws are duplicated, redundant, multiplied, magnified, and contradictory. Laws and regulations covering doctors and hospitals plus all the other parts of our healthcare system now account for over half of all the words, sentences, and paragraphs in our entire body of law.

If regulations could make a healthcare system work better, ours would surely be perfect. In fact, the opposite has occurred. Even those who believe that only government regulation can assure quality health care should face this fact. More laws and regulations are not going to fix our system. If we are truly concerned about the high cost of health care, if we really desire greater safety and higher quality, then we must undertake a dispassionate analysis of the current mess. If we wish to begin effective treatment of our healthcare system, we must first make an accurate diagnosis.

The other main consequence of medical socialism (and other protectionist, centralization or entitlement programs) is that it may just be that the whole system will collapse in some way before you get to the point of needing expensive medicine - you'll think a lot more rationally about future costs in healthcare incurred today if you assume it likely you'll be paying in full.

You should not expect insurance or governments to pay for real anti-aging treatments when they become available. They might do it, or they might not. There are several proposed future scenarios under which the medical insurance industry and government programs are bankrupted or forced into reform by extended healthy life spans. "Forced into reform" is a polite euphemism for "we are not paying for your treatment." The power of compound interest allows you to accumulate a great deal of money before you will need to spend it on retirement and future medical technologies - so make best use of your time and save wisely.

The future is uncertain; you shouldn't count on advances in serious anti-aging medicine arriving in time to make your later life easier, healthier and longer. So look after your health, and raise your voice in support of serious anti-aging research and more effective medicine.

On The Grandmother Hypothesis

A long article from RedNova explains the Grandmother Hypothesis as it relates to the evolution of human life span and reproductive capabilities. Finding an explanation for the comparatively long human life span is one part of wider longevity research - we live longer than other mammals of the same size, but we do know know why this is the case. "There is little question that positive selection has acted on genes that increase lifespan. [However] there is still considerable debate as to whether or not prolonged lifespan has been selected to ensure the survival of offspring (Mother Hypotheses) or to increase the reproductive success of those offspring (Grandmother Hypotheses)."

Link: http://www.rednova.com/news/display/?id=131393

Searching For Supercentenarians

The Post-Gazette profiles the activities of the Gerontology Research Group: "GRG's 40 volunteers - a loose, international network of demographers, gerontologists, epidemiologists and self-styled 'hobbyists' - are dedicated to verifying the ages of the world's oldest people, and to learning the secrets of their longevity. But to do so, they must contend with dishonest schemers, governments that gleefully support false claims and what researchers call 'the invisible barrier of 115.' Because almost no one who reaches age 114 ever sees 115, the group is skeptical of any claims to ages higher than that. ... Dr. Coles believes that if doctors find answers about superlongevity, the pharmaceutical industry will develop drugs to help the oldest of us survive longer."

Link: http://www.post-gazette.com/pg/05059/463487.stm

On Early Alzheimer's Development

(From News-Medical.net). Understanding exactly how Alzheimer's disease develops in its earliest stages is a very necessary first step on the path to early detection and prevention. Researchers are now looking beyond the characteristic amyloid plaques to uncover the causative biochemistry: "Early Alzheimer's disease may be precipitated by a 'traffic jam' within neurons that causes swelling and prevents proper transport of proteins and structures in the cells ... we decided to look at mouse models of Alzheimer's disease early in their life, before plaque formation, to see if we could detect early evidence of abnormal axonal transport ... What we saw quite early in the life of those animals - well before any plaque deposition - were obvious axonal defects."

Link: http://www.news-medical.net/?id=7979

More On Controlling Stem Cells

Forbes has more on recent advances in our knowledge of stem cell differentiation and ability to control it. "In experiments with mice, scientists believe they've discovered a new class of gene signals that either prevent or permit stem cells to develop into specific cell types ... This discovery could lead to new stem cell therapies. We have very little understanding of how stem cells work. This is a small piece of the puzzle of how stem cells maintain their stem 'cell-ness.'" These new insights follow on from recent work linking the biochemistry of graying hair, stem cells and melanomas. "It is fascinating that these embryonic genes are active in adult stem cells. The big issue is, can adult stem cells ever be as multipotential as embryonic stem cells? And we still don't know the answer."

Link: http://www.forbes.com/lifestyle/health/feeds/hscout/2005/02/23/hscout524154.html

A Weekend Dose Of Stem Cell Politics, Part II

More politics for those of you who like to keep an eye on such things; the current state-level battles in the US are likely to set the script for coming attempts to criminalize medical research by federal legislators. It's a strange world we live in, one in which groups of people fight so hard to prevent cures for age-related conditions from being realized.

The debate over embryonic stem cell research in Massachusetts has been getting a fair amount of press in past days. A summary of the pertinent points can be found at Newsweek:

From an academic standpoint, Massachusetts may have the most to lose if stem-cell research is outlawed or discouraged. "At this moment," says Boston-based state Sen. Cynthia Creem, "there are more scientists doing groundbreaking biological and medical research within 10 miles of my desk than in any other city in the world."

...

The governor, whose wife suffers from multiple sclerosis, a potential target of stem-cell research, had met with a prominent Harvard scientist and backed Creem's original bill. But Romney, a Republican rumored to have national political ambitions, stunned stem-cell supporters with a carefully crafted statement. Yes, he would support some forms of the research. But nuclear transfer performed on embryos created solely for research purposes - the most controversial and one of the most promising techniques - was out of the question.

Bioethicist Arthur Caplan dismantles the Govenor's position in his latest column:

In a state with an economy intimately linked to research in the life sciences, a pronouncement from the governor that the kind of stem cell research being aggressively pursued at world-class universities in California, Singapore, the United Kingdom, Israel, China, India and Korea ought not be done in the Commonwealth is going to receive a very cool reception in many quarters.

Meanwhile, funding and other legislative debates continue in Maryland and in Utah.

Being libertarian, I'm not in favor of state funding for anything; I am in favor of various layers of government getting out of the way - the real damage done so far to progress in stem cell research in the US has resulted from the threat of criminalization. This has scared away the vast pool of potential private funding and greatly slowed progress by those companies and new ventures best placed to move ahead with the commercialization of new research. Even now, federal anti-research legislation in the US is still a possibility - all the more reason to speak up in defense of curing age-related conditions through research into therapeutic cloning and embryonic stem cell research.

Just How Important Is Exercise?

Modest exercise is very important for your long-term health and longevity, as noted at Forbes. "Most of the issues we look at as aging really are disuse. We're meant to move ... Exercising is the closest thing to a 'magic bullet,' to ensure longevity and a good quality of life." Calorie restriction is another proven, available way to enhance your healthy longevity. "There is good evidence that older people respond just as well to exercise as younger people do, but most older people don't exercise." By not taking care of your health, you risk age-related conditions that make it much harder to exercise - age-related degeneration is a downward spiral, but even today you have control over how fast it happens and what your risk levels are. To benefit from the longevity medicine of tomorrow you must stay healthy today.

Link: http://www.forbes.com/lifestyle/health/feeds/hscout/2005/02/25/hscout522467.html

Reminder: De Grey Versus Olshansky

This press release provides a reminder that Aubrey de Grey and S. Jay Olshansky will debate the future of healthy life extension in mainstream science on March 30 at BIOMEDEX 2005. "The debate will be examining ageing and human mortality, and already promises to be a lively one. Dr. Aubrey de Grey will be defending the notion that ageing is a treatable disease and that dramatic increases in life expectancy are forthcoming, while Dr. Olshansky will be upholding the thesis that ageing is an inevitable by-product of operating the machinery of life and that life expectancy could begin to decline in the next few decades." Olshansky's position is a little more nuanced than that, as a look at an exchange at Fight Aging! will show.

Link: http://www.cnw.ca/fr/releases/archive/February2005/24/c8233.html

A Weekend Dose Of Stem Cell Politics

Some thoughts to chew over for those of you with a political bent, found at the end of a fairly wonkish article at Newsweek:

For a country accustomed to leading the world in medical research, the loss of momentum for the biotech industry together with the human cost of the stalled research is prompting a fresh attempt at legislation on Capitol Hill. Republican Mike Castle of Delaware and Democrat Diana DeGette of Colorado are introducing the "Stem Cell Research Enhancement Act of 2005," which would allow federally funded researchers to use embryos that would otherwise be discarded by fertility clinics if patients agree to offer them for research. The lawmakers introduced the same bill last year and believed they had enough votes for passage.

Republican leader Tom DeLay refused to allow the bill to come to the floor for a vote, and he is playing the same game this time. The current bill has 156 cosponsors in the House and the support of such staunch Senate Republicans as Orrin Hatch of Utah. It would easily pass in both the House and Senate if it weren't for the stranglehold the right has on Bush and the GOP. If ever there was an issue where Democrats could borrow a page from Norquist's playbook and unite under a single winning banner, this is it.

Politicians only seem able to "fix" a problem of their own creation by piling it on higher and deeper. Politicians and other agents of the state cannot create - all they can do is obstruct and destroy. Meanwhile, private funding for research into curing age-related conditions continues to be deterred by the threat of criminalization. Meanwhile, millions continue to suffer and die.

Following The Debate In Missouri

(From the Record). The fight over anti-research legislation in Missouri has grown heated: "State legislators have introduced bills in both the Missouri House and Senate to ban a technique known as somatic cell nuclear transfer (SCNT), criminalizing certain kinds of research into medical uses of embryonic stem cells in Missouri. SB160 was recently approved by the Senate Judiciary Committee and will go to the full Senate for vote." This article gives a good high-level background to the science and proposed legislation - this is the same sort of fight we can expect to see at the Federal level over the next few years. So watch, learn, and make sure your elected representatives know your opinions on better medical research and longer, healthier lives.

Link: http://record.wustl.edu/news/page/normal/4786.html

On Anti-Aging Hype

The attitudes of conservative gerontologists towards healthy life extension, the loud "anti-aging" marketplace and the serious pursuit of longevity research are summed up in a new book. "The Gerontological Society of America's 2004 peer-reviewed article series on the truth of anti-aging medicine is now available in a single volume. ... Supervised by editors S. Jay Olshansky, PhD, Leonard Hayflick, PhD, and Thomas T. Perls, MD, MPH, this book focuses on the history of anti-aging research, the debate among scientists on the societal implications of modifying the biological rate of aging, and the reality of what is currently known about the aging process. Further attention is given to growth hormones and supplements and legal issues associated with the practice of anti-aging medicine."

Link: http://www.geron.org/press/antiagingbook.htm

Aubrey de Grey on Aging Bacteria

An interesting conversation regarding evidence of aging in bacteria previously thought to be essentially immortal is currently taking place on the Gerontology Research Group mailing list. Biogerontologist Aubrey de Grey had this to say on the topic:

Based on the evidence so far available, I think there is indeed a truly fundamental phenomenon being demonstrated here. It seems likely to me that all unicellular organisms that have cell walls (as opposed to only cell membranes) will behave much as shown in this study, because the cell wall is a heavily cross-linked proteinaceous structure within which accumulating damage does not diffuse (as it does in lipid membranes). If E. coli grow by adding more cell wall at the centre (which I think they do), therefore, increasingly old "poles" will indeed feature an increasing amount of damage (e.g. extra cross-linking and hardening). (Note that the authors' use of "pole" is possibly misleading, as that term normally applies to the tip of the mitotic or meiotic spindle, a structire not present in bacteria.) So in hindsight (presuming that the above turns out to be true), this is (just as Pete Estep said) a case where we fell too in love with the natural hypothesis in the absence of data. Rather like the inability of one mutation to extend lifespan, which Tom Johnson had such a hard time in getting the field to accept back in 1988. But note, it doesn't apply to animal cells, as they don't have cell walls. So a crucial thing to do is to repeat this experiment with single-celled animals.

...

It's probably the most talked-about scientific publication of the month, in fact. It's certainly very exciting, but various details need to be kept in mind at this stage:

1) The experiment was done for eight generations and showed a linear decline in the growth rate with increasing numbers of generations in which the old pole was inherited. This is in contrast to the standard pattern in aging where the functional decline accelerates with age. It is thus very important to extend this study to 20 or 30 generations to see whether the trend eventually accelerates or levels off. Of course the entire lineage does not need to be followed -- one just needs some cells at each point in the virtual lineage.

2) The authors measured "growth rate", and they really do mean rate of increase in the size of the cells. However, they note that new-pole daughters are larger on average than old-pole ones, and additionally that the new-pole daughter tends to divide first. The latter is to be expected, since increase of size is generally limiting for generation time for bacteria in rich medium. This merits a lot more discussion (for example there is nothing about whether multi-generation-old-pole cells are especially small), because the whole result may be because smaller cells grow more slowly at first (not that that wouldn't be interesting, of course). The authors describe the above results as showing that there is no "juvenile phase" whereby the new cell needs to go through some initial maturation process before it gets going, but they forget that it may be the daughter with the old pole that is going through such a phase.

3) The authors allude in the discussion to the phenomenon constituting a 2% "cost" of the aging process at the population level. They don't elaborate, but I think the meaning must be that the colony would grow 2% faster if all cells grew as fast as the new-pole ones. But this is not the right calculation if one wants to determine cost, because if the divisions were precisely symmetrical then the old-pole cell would grow faster but the new-pole cell would grow more slowly. I haven't done the maths but I strongly suspect that asymmetrical division (and hence asymmetrical dilution of damage) can for some examples of the function linking growth rate to damage levels confer a higher colony growth rate than symmetrical division.

4) Possibly the main reason the above points matter so much, especially the last one, is because of the effect on the validity of concluding that the observed phenomenon is universal, inescapable etc. There are numerous circumstances in which an organism's optimum metabolic tactics vary non-linearly with stress: for example the increase of maintenance at the expense of reproduction in caloric restriction, or the fusion response of mitochondria to high stress, or the senescence response of cells to over-frequent double-strand breaks. I suspect that under a variety of alternative, reasonable assumptions, the colony growth rate would switch from being best with symmetrical division to being best with asymmetrical division depending on whether stress (e.g. oxidative) and hence rate of damage accumulation was above or below some threshold. If so, repeating this experiment under low oxygen might give different results.

Steps Towards Replacement Organs

The Telegraph reports on another small - but complex and significant - step forward towards growing replacement organs from a patient's own cells. "Researchers in Japan have succeeded in cloning a human kidney by cultivating human stem cells extracted from adult bone marrow into rat embryos, team members said. The development is expected to increase the possibility of expanding regenerative medicine to anatomically complicated organs such as the kidney and lung as a potential means to treat patients with disorders of those organs." This sort of work with animals is running in parallel to other efforts that focus on tissue engineering and nanoscale material scaffolds.

Link: http://www.telegraphindia.com/1050224/asp/foreign/story_4417769.asp

Stem Cells, Front and Center

Andrew Lynch pointed me to a New York Times article profiling Hans S. Keirstead; you may recall I've mentioned his research into curing paralysis using embryonic stem cells at the Longevity Meme.

Dr. Keirstead, an assistant professor at the University of California campus here, has been making paralyzed rats walk again, using a treatment based on human embryonic stem cells. Next year he and his corporate partner, Geron, plan to try treating people who have recent spinal cord injuries, in what would almost certainly be the first human trial of any therapy derived from such cells.

"You've got a patient community out there that is in desperate need," Dr. Keirstead said in an interview. "If the treatment is safe, let's get it out there and try it."

And to those who argue that it is too soon to test his technique on humans, he has an answer. "There will always be people who say slow down, slow down," he said. "I guarantee you none of them have relatives in wheelchairs."

Human nature being what it is, we see the same thing happening for research into healthy life extension and cures for age-related degenerative conditions. The folks standing in opposition aren't the ones suffering...

Update On Mitochondrial Research

Betterhumans provides an update on some of the more interesting research into mitochondrial regeneration. "Halting aging and the development of diseases such as Alzheimer's and Parkinson's may one day be as simple as seeing the doctor for a mitochondrial 'tune up.' The tune up, currently in the early stages of development, would repair mutations that occur in mitochondria and are believed to contribute to many afflictions, from diabetes to heart disease." The timeline is still long, however: "Once we prove the efficacy of [mitochondrial DNA repair] in animals, we need to show that it works in humans and then expand its use to other conditions, which should be enough to keep us busy for the next 15 to 20 years."

Link: http://www.betterhumans.com/News/news.aspx?articleID=2005-02-23-3

The Downside of Discussing Immortality

I recently mentioned a little of the upside relating to public discussions of biological immortality (a state of agelessness, not invulnerability) - this in connection to the "suitable outrageous extreme." In essence, the presence of a serious discussion about the science of a cure for aging and a post-aging world creates an environment in which is is easier to gain support and raise funding for more modest research into extending the healthy human life span. This more modest research still happens to be the first step on the road to a cure for aging. Talking about the end goal speeds the journey by increasing public acceptance and thus driving funding. In that sense, I'm all for the responsible discussion of biological immortality through medical technology - curing aging, in other words. On the other hand, talking about immortality rubs some intelligent, well-meaning folks the wrong way right off the bat. Two good examples are here:

We can see that this fellow is so repulsed by something that is "obviously" fringe that he throws out or refuses to investigate associated facts and science - despite coming across as someone who would be sympathetic to a more subtle approach. For example:

To these concerns, de Grey would no doubt say, "Don't give me possible problems that might or might not happen. Give me the possibility of problems that might or might not be so bad that it's preferable to carry on condemning 100,000 people a day to death, forever."

If there's one thing I hate more than brute force, it's brute reasoning. I wonder how many of those people die from war, famine, car accidents, political prosecution, disease or other factors a genetic code for immortality wouldn't solve. Come to think of it, how are we supposed to get the secret of immortality to people who can't even get clean water? Or how are we going to stop wars? Sure doesn't look like finding immortality is going to do a lot to reduce that amazingly large questionably calculated number.

A few moments of research would uncover that, yes, approximately 100,000 people each and every day could be saved by a cure for aging and age-related degeneration. Another 50,000 each day die from violence, non-age-related disease such as malaria, and other consequences of politically-imposed poverty - but you can't hold back progress on account of poor distribution strategies and bad politics. That's simply reaching for all the old, disproved arguments against any new technology. A rising tide raises all boats, and the building of better boats is a separate topic from raising the tide.

There's much more in that and similar veins of course, the sort of thing an educated person would pick up from filtering the public opinions of scientists and a little knowledge of science through a prexisting bias that any talk of a cure for aging is "fringe" or "cultish." The question would be what we advocates can take away from this view point. What can we learn? From my observations, this sort of reaction is in a minority compared to more positive responses - especially when balanced against the "outrageous extreme" effect of a discussion of immortality on public support for near-term healthy life extension goals. Still, is there a good way to gain the support of people like this while continuing to educate the public about the possibilities offered by healthy life extension research and the fight to defeat aging?

Anti-Research Groups Attack CIRM

(From AZCentral). Groups opposed to embryonic stem cell research and therapeutic cloning are attempting to derail the California Institute for Regenerative Medicine through a variety of legal avenues - none of which are related to their actual ethical objections to the research, of course. "One lawsuit alleges the California Institute for Regenerative Medicine violates state law because it's not governed exclusively by the state government, and the committee that controls the research money it will dole out isn't publicly elected." Personally, I can't help but feel that people who prioritize unthinking, unfeeling clumps of a few cells - no different from the skin cells you shed each and every day - above the continuing suffering and death of millions have their ethics all backwards.

Link: http://www.azcentral.com/news/articles/0223stemcells23.html

Progress In Nerve Regeneration

As noted at EurekAlert, "for the first time, scientists have regenerated a damaged optic nerve - from the eye to the brain" in mice. Regeneration of large amounts of nerve fibre is still a hurdle - and vital to any effective future therapy for many injuries and conditions relating to nerve damage - but this is a promising stem forward. "Chen and her research team have dedicated themselves to learning the reasons why [central nervous system] tissue stops regenerating and to finding ways to reverse that process, using the optic nerve as their research model. ... [new techniques] caused the optic nerves to return to an embryonic state and stimulated rapid, robust regeneration of the optic nerve - again, as with the younger mice - within only a few days."

Link: http://www.eurekalert.org/pub_releases/2005-02/seri-ssr022305.php

Protein Experiments In Mice

Betterhumans reports on the latest in a line of studies in mice to determine the effects of regulatory proteins on muscle, fat and bone development. "A protein that blocks the production of fat in mice also gives them a bone mass four times that of normal mice, hinting at new ways of treating osteoporosis in humans. ... [It] is part of a family of 19 proteins that regulate changes that take place as embryos develop. ... Otherwise, say the researchers, there didn't appear to be any abnormal features in the bone." It is a fair way from experiments such as these to producing gene therapies for humans that address age-related degeneration - but scientists have to start with the basics.

Link: http://www.betterhumans.com/News/news.aspx?articleID=2005-02-21-4

More Long-Lived Animals

EurekAlert reminds us that many animals have very long life spans - 250 years in the case of a particular breed of tubeworm. Whales are also surprisingly long-lived and you'll find a great deal more interesting information of this sort at the Ageless Animals website. That so many different species of animal live so long is a clear rebuttal to many of the arguments against healthy life extension. The basis of the complex machinery making up our bodies is clearly capable of extreme longevity in other configurations - many of these very long-lived animals are not so different, biochemically speaking, from us humans.

Link: http://www.eurekalert.org/pub_releases/2005-02/plos-tst021605.php

On Social Security and Age-Related Frailty

Jay Fox weighs in on social security and age-related frailty:

Can this be avoided? Ironically, people who oppose life extension technology - i.e., people who claim to value the dignity of human life and of our elders - are the very people who may ensure that this collapse arrives. People who oppose life extension and medical research are in fact going to cause frail people to overburden society to collapse. Needless to say, society will not go down without a fight, and frail people are the ones who will suffer at the hands of the disenfranchised young.

If you truly care about our elders, you owe it to them to make sure that we find a way to prevent the crisis of the impending tsunami of frail people that will flood society in the next 50 years. You owe it to them to find a way to make frailty the exception among the extremely old, rather than the rule.

I've had my say on this before; quite aside from pointing out that all these "problems" could be dealt with through individual choice in insurance and charitable giving, it strikes me that the light and noise surrounding the social security debate is simply more displacement behavior. Most people work very hard to avoid thinking about the realities of age-related degeneration and its consequences, sad to say. This is a big problem, since this sort of attitude helps to delay work on a cure for aging - large scale research requires a vocal, supportive, educated public.

Glenn Reynolds is another person echoing these sorts of thoughts:

Plague, of course, was once seen as inevitable, and there were even those who thought that efforts to fight it represented a challenge to God's will. We got over that, and I think we should recognize that aging is just another disease that science can't address -- yet.

But as the developed nations face a huge unfunded retirement liability, lots of people are talking about extending the retirement age to cut down on payments. I wonder if we might consider extending the retirement age through making people live longer, healthier lives -- perhaps by diverting a small portion of retirement money into aging research.

As is Randall Parker:

Given that the four major alternatives discussed above have major downsides why not consider science as a potential solution? After all, science will eventually produce solutions that cheaply cure or prevent all the major diseases. The only question is when. Acceleration of the rate of advance could not only reduce the size of future liabilities but could also have the very attractive added benefit allowing us all to get healthier and stay healthier for much longer.

...

My modest proposal for funding medical research: Change the major medical entitlements programs to require that 10% of all medical entitlements budgets go to fund medical research. Then when medical entitlements spending inevitably goes up medical research spending will go up proportionately. Yes, that will make the financial numbers for the medical entitlements programs look worse in the short run. But the money thereby spent will produce much larger savings for those programs in the longer run and will also produce treatments that will lead to great improvements in the health of the vast majority of people.

Nanomedicine On The Horizon

The Nashua Telegraph takes a look at early nanomedicine - which is to say improved nanoscale manufacturing techniques applied to medicine. "'Nanobots' remain imaginary for now, but a number of other futuristic nanodevices are already proving their potential in animal and human experiments. More than 60 drugs and drug delivery systems based on nanotechnology, and more than 90 medical devices or diagnostic tests, are already being tested." Molecular manufacturing and true nanomedical robots are still decades away despite the efforts of well-known researchers - and the promise for healthy life extension - but diagnostic technologies are currently improving rapidly.

Link: http://www.nashuatelegraph.com/apps/pbcs.dll/article?AID=/20050220/ENTERTAINMENT/102200054

Weight Increases Dementia Risk

(From the Life Extension Foundation News). Here is another reminder that excess weight at any point in life increases your chance of suffering age-related degenerative diseases. "People who gain even just a few extra kilos/pounds when they reach middle-age increase their risk of developing dementia later in life, according results from a new Swedish study ... Based on data collected over a 28-year-period from more than 7,000 men in the southwestern town of Gothenburg, the study reveals a clear link between middle-age weight-gain and later deterioration of intellectual faculties. ... The link between weight-gain and dementia remained clear even after factors like smoking, exercise and diabetes had been taken into consideration."

Link: http://www.lef.org/news/LefDailyNews.htm?NewsID=1865&Section=NUTRITION

Footnote to the Footnote

The UN has issued its non-binding declaration calling for bans on therapeutic cloning, the last gasp for US-backed efforts to craft an international treaty criminalizing this important medical research. A few quotes from Wired, which wraps this into the broader topic of science and politics in the US:

The politicization of science policy in the United States has become a contentious issue in the past several years, with groups like the Union of Concerned Scientists criticizing the Bush administration for favoring political interests over scientific results. Now, that trend seems to be making international inroads.

Nations including Singapore, South Korea, Belgium and the United Kingdom blasted the declaration by the divided U.N. committee, calling it political posturing.

...

"In the scientific community in other countries we are ridiculed," said Kurt Gottfried, chairman of the Union of Concerned Scientists, in an interview. "It has certainly lowered our prestige across the world."

U.S. delegates to the United Nations supported a treaty to ban all cloning starting in 2002. After nearly two years of negotiations, the U.N. shelved attempts to agree on a treaty and instead delegates opposed to cloning pushed for a non-binding declaration as a compromise.

...

The United States is becoming notorious in the eyes of other countries, Gottfried said, as a nation that has allowed ideology to become a premise for science. That perception is sure to have harmful repercussions on the American science community, he said. Scientists are already leaving the country and graduate students are less uninterested in studying in the United States, he said.

South Korean politicians have declared they will not interfere with therapeutic cloning research:

South Korea will continue its stem cell research despite the anti-cloning resolution of a U.N. committee, according to the Ministry of Health and Welfare Monday.

"It is just a non-binding declaration and we have no plan to review our policy of allowing therapeutic cloning," the ministry's manager Kim Heon-joo said.

...

When contacted, Hwang's team echoed the stance of the health ministry, saying the U.N. resolution is simply a recommendation and that they would continue with their cloning research.

"We don't know much about the U.N. decision but we don't feel bound by it. We will continue our stem cell research as long as Korea sees it as legal," said SNU professor Kang Sung-keun, one of Hwang's top lieutenants.

Mechanisms Of Osteoarthritis

EurekAlert: researchers have found that joints whose cartilage lacks a specific type of collagen will develop osteoarthritis - the so-called 'wear-and-tear' form of the disease - at a greatly accelerated rate. The results of their experiments with mice provide new insights that could lead to potential treatments for a disease that afflicts more than 40 million Americans." This is early stage research, in the sense that a link has been identified and mechanisms to explain it proposed - but it's way to go from here to deploy working regenerative medicine for this form of arthritis. "While the mechanism behind the accelerated development of osteoarthritis is not yet clear, it suggests that the lack of type VI collagen negatively impacts the ability of the cartilage to respond properly to the mechanical stresses and pressures on the joint."

Link: http://www.eurekalert.org/pub_releases/2005-02/dumc-los021505.php

On Upb10 And Telomeres

The LEF News is reprinting an interesting illustration of cellular complexity. "Genomic instability, particularly in the regions at the ends of the chromosomes known as telomeres, has been linked to aging in humans and an elevated risk for aging-related diseases, the most prominent of which is cancer. ... an enzyme known as Ubp10 plays a vital role in protecting the telomeric regions of the genome from potential destabilizing molecular events. ... Interestingly, Ubp10 appears to work similarly and in concert with another enzyme called Sir2 ... Sir2 has also been associated with promoting genomic stability, and some studies have linked it intriguingly to the aging process. Some studies, for example, have suggested that low-calorie diets that extend life also boost Sir2 activity dramatically."

Link: http://www.lef.org/news/LefDailyNews.htm?NewsID=1856&Section=AGING

Stem Cell Research Update, Outsourced

A fair amount has been happening in the US and elsewhere of late regarding stem cell research, funding and legislation. Fortunately, I don't feel so obligated to run off updates to these things now that a number of other folks are doing an excellent job in this area. Stem cell research has always been of great interest to me because it leads to regenerative medicine, which leads to cures for a wide range of age-related conditions ... which leads to incidental (rather than directed) healthy life extension. In addition, the research and capabilities required to make stem cell medicine a reality dovetail very nicely with the research and capabilities required to cure aging - it all comes down to understanding and controlling our cells in the end. So a focus on stem cell science (and legislation) isn't really as core to Fight Aging! as a focus on longevity science - I'm glad to see other people working on it. Some frequently updated blogs and news sources worth following:

A last note: now that things are heating up once more at the Federal level in the US, isn't it time you faxed your representatives to protest attempts to criminalize therapeutic cloning and embryonic stem cell research? The threat of anti-research legislation over the past few years has caused great harm to private funding - the cost of imposed delays in research into cures for age-related conditions is very high. You have a voice and can do something about this!

Another Clever Use Of Gene Therapy

EurekAlert reports that scientists have successfully used gene therapy to get mice immune systems to accept grafts of dead bone (a common procedure for drastic bone loss in humans). "Everyday activities cause microscopic fractures in our bones ... when the bone is dead, there is no healing, and those tiny fractures begin to accumulate until finally, perhaps in 10 years, the implanted section collapses, and more drastic surgery becomes necessary. ... the virus permeated the inflammatory tissue around the dead bone and turned on the genes. The mouse body then began to treat the implanted bone as if it were its own tissue instead of a foreign object ... It's at that point that the body actually begins changing the dead, foreign bone splint, into the body's own, whole, living bone."

Link: http://www.eurekalert.org/pub_releases/2005-02/uorm-gtc021805.php

Growing Support For Stem Cell Research

Public support for embryonic stem cell research is still growing in the US - a hopeful sign that in this case, as for others in the past, people do not refuse the chance of cures for age-related disease. "More than three out of five Americans (63 percent) now back embryonic stem cell research, and even higher levels of support exist for bipartisan federal legislation to promote more such research (70 percent) and the growing number of state-level initiatives to encourage stem cell work (76 percent do or might support such measures), according to a
new survey." A pity that support is usually portrayed in terms of public rather than private funding, but this level of awareness and enthusiasm is certainly an improvement over the state of play just a few years ago.

Link: http://www.prnewswire.com/cgi-bin/stories.pl?ACCT=109&STORY=/www/story/02-15-2005/0003022386&EDATE=

Enumerating The Benefits

(From the Kansas City News). Estimating out the number of people likely to benefit from near-future regenerative therapies developed using therapeutic cloning - or somatic cell nuclear transfer - is a good tack to take in political debates, as is happening in Missouri. "A study has found that more than 400,000 Missourians suffer from six diseases and injuries that could be treated or cured with therapies that scientists expect to develop using somatic cell nuclear transfer. ... The study, conducted by The Analysis Group, a national research firm, looked at six medical conditions that are considered most likely to benefit from future stem cell research: juvenile diabetes and a related disease that develops in adults; Parkinson's diseases; spinal cord injury; heart attack; stroke; and Alzheimer's disease."

Link: http://kansascity.bizjournals.com/kansascity/stories/2005/02/14/daily42.html

Federal Fight Over Stem Cell Research

Reuters reports on new legislative initiatives in the US: "Aiming to circumvent President Bush's limits on the use of stem cells from human embryos, members of Congress on Wednesday introduced bills to allow federal funding of embryonic stem cell research. Supporters from both major parties joined the coordinated introduction in the House of Representatives and Senate, saying they have given up on persuading Bush to change his policy. ... Feinstein said she and other senators also planned to introduce a bipartisan bill to encourage so-called therapeutic cloning, or somatic cell nuclear transfer. This technique produces stem cells directly from a patient. Bush has said he plans to work to outlaw it completely."

Link: http://olympics.reuters.com/newsArticle.jhtml?type=scienceNews&storyID=7652383

Good Commentary From Randall Parker

As always, good, thoughtful commentary from Randall Parker on some recent advances in stem cell research:

Pig Embryonic Cell Transplants May Work For Humans

My guess is that in the future both the use of starter cells to grow replacement organs in a human body and the transfer of fully grown xenotransplants will become commonly used treatments for organ failures. These treatments might even be used in a complementary fashion. Get an emergency full sized xenotransplant organ with immunosuppressive drugs to meet an immediate emergency need and then once the patient is stabilized and healthy transfer in some more immunologically compatible cells to grow yet another organ that will serve as the permanent replacement.

In the longer run it seems reasonable to expect the development of techniques that allow the growth of full sized immunologically compatible organs. Alternatively, full sized organs will be grown up and then immune system modification therapies will be developed that will be able to adjust an immune system to teach it that a transplant organ should be treated as native tissue.

I'm not so confident here; my suspicious is that the level of biomedical competence required to overcome the various hurdles associated with xenotransplantation will also allow organs to be grown from scratch from a patient's own tissue or remove obstacles associated with immune rejections between humans. From my admittedly distant position of viewing, it looks like scientists have about the same level of work remaining in any of these fields.

Young Mice Blood Turns On Regenerative Ability Of Old Mice Muscle

This is an important report. But I repeat my caution above: If the presence or absence of some compound(s) in the blood is reducing the repair ability of a variety of tissue types (and it seems likely other tissue types will also be found to be affected by young versus old blood) then there is a decent chance that this reduction in repair ability was selected for to achieve some benefit, most likely a reduction in cancer risk.

...

Suppose that changes in levels (either increases in suppressor molecules or decreases in cell growth stimulating molecules) of one or more compounds in the blood as we age happens in order to reduce the risk of cancer. Well, this is problematic for hopes to derive maximal benefits from replacing aged stem cell reservoirs with youthful stem cells. The old stem cells could be replaced with younger cells. There'd be immediate gains from lowered risk of cancer and relative improvements in the vigor and health of adult stem cells. So that is still worth doing. Yet the young replacement stem cells would still be restrained by levels of compounds in the aged blood. Here's the problem: If some but not all stem cell reservoirs have their stem cells replaced with younger stem cells it might not be safe to change the blood to make it more like young blood. It might be necessary to rejuvenate all stem cell reservoirs before the blood can safely be made more like young blood.

Here is an analogy: Imagine you have a car. It is old and it has 4 bad axles that will fall off if the car is driven too fast as well as a steering column that will fall apart at high speeds. Suppose you know how to replace the 4 axles but not the steering column. Well, if you replace only the 4 axles you still can't safely drive your car at high speeds. But with humans this problem is even tougher because there are many stem cell reservoirs located near every muscle and organ that would need to be rejuvenated before they could all have their level of stimulation by the blood safely raised to youthful levels.

Once really effective anti-cancer treatments (even treatments that kill all precancerous cells) are developed then most (all?) safety worries from making blood young again would go away. Any cancers that popped up in response to having youthful and growth-stimulating blood could quickly be slain or they could be slain even before the blood was rejuvenated. So great cancer-slaying treatments would make rejuvenation treatments easier to implement.

Xenotransplantation Of Stem Cells

National Geographic News reports on the prospects for using pig embryonic stem cells to regrow damaged human tissue. Xenotransplantation is beset by all sorts of biochemical obstacles, but medical science is advancing to the point at which we can start to see ways around these roadblocks. "By implantation of pig embryonic tissues into immune-deficient mice, we have now determined for the first time distinct gestational time windows for the growth of transplanted pig embryonic liver, pancreas, and lung precursor tissue into functioning tissue ... Using pig tissue to replace failing human organs could help patients with diseases such as diabetes, Parkinson's, and liver failure."

Link: http://news.nationalgeographic.com/news/2005/02/0215_050215_transplant.html

Connecting a Field of Research With a Pool of Money

It is always good to see a high-value application emerge from a field of science that will eventually lead to healthy life extension, even if that application itself doesn't have any effect on our life spans. Applications are bridges to pools of money and consumers - the process of serving those consumers helps to fund and broaden the underlying science. Cloning animals (especially pets) is a good recent example, as is stem cell based hair restoration. Wired offers another potential application of stem cell science that could tap into a large pool of money: breast implants.

What could be better than breast implants? Why, breast implants that continually repair themselves, of course. Saline implants can leak, rupture, interfere with mammograms, and lose their shape. But scientists are studying ways to make breast augmentations from stem cells, which are famous for their self-renewing capabilities. Researchers at the University of Illinois at Chicago will publish a study in the April issue of Tissue Engineering showing that stem-cell tissue implants in mice kept their shape longer than traditional implants.

Younger fields of research need as many of these lucrative bridges to money and consumers as possible in order to grow the pool of funding, scientists and knowledge. Private funding is quite capable of outweighing public funding, but it won't come out to play in the absence of a clear, defined market.

Young Blood For Old Muscles

A fascinating experiment with genetically identical mice of different ages demonstrates that an influsion of young blood helps old muscles to heal as though they too were young. Wired reports that researchers "must pinpoint the youth-inducing molecules in the blood that are responsible for switching on the stem-cell capabilities in old muscles. Rando said that grueling process will be his lab's next project. ... Rando and his colleagues studied muscle stem cells called satellite cells, which in young mice and humans induce repair when injury strikes. Rando found in previous work that satellite cells exist in older muscle, but they don't respond to a muscle's cry for help after injury. In the new study, the presence of younger blood helped the satellite cells work more like they do in young mice."

Link: http://www.wired.com/news/medtech/0,1286,66615,00.html?tw=wn_tophead_2

Another Interview At The Eagle

A Telegraph reporter caught up with biogerontologist Aubrey de Grey at the Eagle - the scene of a number of past interviews - to discuss his predictions for the future of longevity research. "Two people die every second, one of them from diseases that would not afflict a young person. That means that 100,000 people die unnecessarily every day. Or 30 million a year. ... De Grey thinks he can save these lives. In his assessment, there are only seven fundamental kinds of cell damage that occur in ageing (generating such side effects as arthritis, diabetes, cancer). He maintains that we have - or soon will have - practical solutions for each of them." If you support work towards longer, healthier lives, then donate to the M Prize for anti-aging research - help the science move faster!

Link: http://www.telegraph.co.uk/health/main.jhtml?xml=/health/2005/02/16/hage16.xml

University of Alberta Talk a Success

Aubrey de Grey's presentation at the University of Alberta went well by all accounts. April notes:

When people begin to ask questions about the consequences of curing aging as we know it, it signals to me that they can't refute de Grey's arguments about the *possibility* of curing aging, so they turn to arguing about the *desirability.* It is indeed hard to refute the basic premise that if we could repair the damage caused by being alive, there's no reason to believe that we can't continue being alive indefinitely (or until we get squashed by a truck on the New Jersey Turnpike.)

The problem with arguing about the *desiribility* of curing aging is that it requires one to argue that people have the moral obligation to die. We would never say to a representative of the American Heart Association that curing heart disease is bad because it would cause lots of people to live longer. We would never tell a nurse who works in the neonatal ICU that it would be better for those palm of the hand-sized babies to die instead of growing into healthy, productive adults. So why should we argue that just because someone is 80, or 90, or 100, or 110, or 150, they should make the planet less crowded by going off somewhere to die?

For me, watching from afar, the most interesting part of this event was the comparatively large amount of globally accessible press attention it generated - which in turn is reflected in the blogosphere - all due to the hard work of volunteers and this useful internet thing you might have heard of. It shows that even comparatively minor events can be used to very good effect in continuing attempts to educate the public ... when the media are appropriately prepared and cultivated, that is.

Adjusting Free Radicals In Flies

Betterhumans reports on efforts to extend fly life span through a "genetic manipulation that reduces free radical damage to nerve cells ... The life extension appeared to derive from an increase in mitochondrial uncoupling in the flies' heads, which led to a decline in free radical production and oxidative damage." It is interesting to see manipulation of mitochondrial function in this way, focused on reducing the damaging waste output - as the authors note, "Our findings highlight the plasticity of mitochondria and suggest the intriguing possibility that genetic or pharmaceutical interventions altering mitochondrial respiration in adults could have significant positive effects on healthy lifespan."

Link: http://www.betterhumans.com/News/news.aspx?articleID=2005-02-15-3

A Pro-Death Distillation

As a counterpoint to a flurry of articles on healthy life extension and biological immortality (or vulnerable agelessness) in the past week, here is an editorial that neatly distills a number of different (and debunked) pro-death ideas into a few short paragraphs.

Humanity has always found its greatest triumphs, if not its very reason for being, in struggle. Those regarded as our greatest leaders - people like Churchill, Lincoln, and in Canadian terms, Trudeau - are defined more by what opposed them than what they did. Much of invention is born from a struggle of some kind or another, whether it's against nature or just trying to get information out quicker. Even in our everyday lives, competition inspires us to something more; we'll often try harder or do better when we have someone or something we're trying to best.

And with the removal of the threat of death, we'll have done away with arguably the biggest competition we have. One doesn't need to point out the countless works of art, to say nothing of entire philosophies, that have tried to come to grips with man's mortality. Ignoring the obvious religious significance of such an event, if man no longer fears death, what reason does man have to continue living? We'll have, for lack of a better term, won.

This isn't to say that the arrival of an elixir of life will be met with mass suicides and depression across the world. No, people will probably continue on pretty much as is, but that would be precisely the problem. Things would stagnate; people would find no reason to do much of anything. Why work, why create, why learn, why suffer, why strive, why believe, why love, why hate, when in the end, it's likely those who take the safest path will end up ahead, in the form of living longer? The world will be locked in permanent suburbia, where too much or too little will lose out in favour of just enough.

Obviously, this happens enough in our world as is; people will almost always settle for mediocre over something that might just be good, but might also be bad. But now, at least, there is one thing that can push us into something more: the fact that, eventually, we're not going to be around anymore. If nothing else stirs us, at least the cold, hard truth of mortality will give rise to something more than sitting on the couch.

But to remove that, to remove the one thing that humanity has always struggled against, is to take out something that is essentially human. If this ever happens, we might just live forever, but I doubt we'll have any reason to.

How silly! How shortsighted! An infinity of far, far greater challenges awaits us after this comparatively simple fix for less desirable characteristics of our biology - exploring the solar system, traveling to the stars, cataloguing all life on Earth, terraforming mars, understanding the roots of intelligence, building a science to determine whether or not we have free will ... I could go on. Personally, I'd like to be around and in good health to try my hand at helping to overcome a few of these future challenges.

More to the point, you, oh writer of editorials, may feel this way, but a great many people fail to share your pessimism, lack of foresight, world-weariness and death wish.

Defending Freedom Of Research

An excellent op-ed from the Joplin Independent hits the right notes: "Rep. Emery seems to believe that a small group of undifferentiated cells - with no brain or nerve cells, no awareness, no thoughts or feelings and never destined to be implanted in a human womb - is the same thing as a human baby. Because of his belief, which to me defies common sense, he would halt medical progress and condemn our children and grandchildren to the same diseases, the same pain and suffering that we face today. We can do better; we should do better; as a state, we must do better. [Therapeutic cloning] is the bright hope of regenerative medicine, and if pursued diligently, it could someday empower physicians to do more to restore their patients' health than previous generations dreamed possible."

Link: http://www.joplinindependent.com/display_article.php/stowers1108408311

Enthusiasm For Private Bioengineering

Articles like this one from MSNBC show that the investment community is warming up to at least some regenerative and tissue engineering technologies required for future healthy life extension medicine. "Cellular Bioengineering has developed a process for growing corneal tissue, which may someday eliminate the need for human donors. It is creating a cell bank that would enable cells from one donor to generate enough supply for 1,000 recipients. ... The company expects to begin human clinical trials in 2006. An estimated 10 million people suffer from some type of corneal blindness, which can usually be cured by transplanting corneas from donors who have arranged to donate their organs after death."

Link: http://msnbc.msn.com/id/6967000/

Gene Therapy For Deafness?

(From the Telegraph). Our ability to hear depends on hair cells in the inner ear: "Normally, humans are born with about 50,000 hair cells but since they do not regenerate, the steady loss that can accompany ageing produces significant hearing deterioration in about a third of the population by the age of 70." Fortunately, scientists have demonstrated - in guinea pigs at least - that gene therapy can be used to coax these hair cells into growing once more. "Now Dr Raphael and colleagues have shown that a type of cold virus, called an adenovirus, can be used to implant a gene, Atoh1, and induce new hair cells to grow in the cochleas of deafened guinea pigs. The gene helps guide development of the ear. In a second study, another American has found that the deletion of a specific gene permits the growth of new hair cells in the inner ear."

Link: http://www.telegraph.co.uk/news/main.jhtml?xml=/news/2005/02/14/wgene14.xml

Finding Progenitor Stem Cells

As the sophistication of biotech tools increase, scientists are identifying more sources of stem cells for regenerative medicine. Here, Nature reports on the discovery of small numbers of heart progenitor stem cells that remain in the adult body. "These are very rare cells, which accounts for why they have not yet been reported ... Only a few hundred progenitor cells remain in the heart after birth, and this number decreases with age, the researchers say. Unlike stem cells, which have a seemingly unlimited capacity for self-renewal, progenitor cells undergo a finite number of divisions ... cardiac progenitor cells have one considerable advantage over stem cells: scientists can easily coax them into becoming fully specialized heart-muscle cells, without chemical or hormonal stimuli."

Link: http://www.nature.com/news/2005/050207/full/050207-8.html

Advance of the Suitable Outrageous Extreme

Back at the end of 2003, I proposed that we need a "suitable outrageous extreme" in our promotion of healthy life extension.

The middle of the road, "reasonable" position in public or political debate tends to gravitate to midway between what are perceived to be the two opposite outrageous extremes, regardless of the actual merits of any of these positions.

With this in mind, it is occurring to me that part of the ongoing problem in the modern political debate over healthy life extension is that our "outrageous extreme" has always been a tentative, reasonably proposal that medical research carry on and that near-term technology would seem to allow us all to live a little longer ... say, to 150.

I mentioned Aubrey de Grey's figure of 5000 years for the life span of an ageless human (based on accident rates - you can find more information on that sort of calculation in "The Tithonus Option is Not an Option" at the Longevity Meme) as a suitable outrageous extreme at the time. I was pleased to see a recent example of this sort of psychology at work in an amusing column at the National Review:

Here we are talking about the federal retirement system facing possible disaster because a lot of people are living into their 80s and 90s. Meanwhile, out in the real world of science, medicine, and hypercompetitive Americans, 90 years old is already peanuts.

...

Normally skeptical journalists are reduced to goo by any news from the longevity frontier. Who cares if a lot of the science is dubious and contradictory? There's a massive audience for this stuff, and the media are only too happy to provide it, quality be damned. Now, with Baby Boomers on the verge of oldster-hood, there's a lot more to come.

Cautious longevity scientists say that it may soon become common for people to live up to 100 or 120 years. Bolder optimists extend it to 150. And there's the prominent inventor and futurist Ray Kurzweil, who takes 250 vitamins a day and co-authored the recent book Fantastic Voyage: Live Long Enough to Live Forever. The book, which got serious coverage in elite media outlets, contends that if we can just all live another 20 or 30 years, we'll be in the age of "intelligent nanobots," tiny machines that will go into our bodies and eradicate all disease and damage, allowing us, potentially, to live forever.

Between these extremes is a Cambridge University scientist named Aubrey de Grey, who has said that people born in the next century (i.e., beginning 95 years from now) may have a life span of 5,000 years.

So 5000 years is now "between these extremes" and must thus be a sensible prediction, never mind the underlying science. While despairing of any attempt to inject rational, factual discourse into mainstream journalism, I think that we are making progress in the marketplace of ideas. That progress will translate to an easier time for scientists working on longevity medicine - when people are producing good science to back up projected future life spans in the thousands of years, proposals for funding to extend the healthy human life span by a few decades look quite reasonable.

Footnote On UN Cloning Ban

ABCNews discusses the aftermath of failed attempts to ban therapeutic cloning at the United Nations - in essence back to business as usual. "U.N. diplomats, deadlocked for years over the drafting of treaty to ban the cloning of human beings worldwide, open negotiations on Monday on an alternative that would instead urge each government to adopt its own laws on human cloning. ... The U.S. campaign to persuade the 191-nation U.N. General Assembly to approve a broad anti-cloning treaty ran out of steam last November." In the US, we still face the prospect of a federal ban on this most promising research into cures for age-related conditions - it's not too late to speak up in support of freedom of research and medical progress.

Link: http://abcnews.go.com/Technology/wireStory?id=495707

Leonid Gavrilov on Funding and Advocacy

Some very characteristic comments from aging researcher Leonid Gavrilov over at Longevity Science:

Where are the generous sponsors and philanthropists willing to support human longevity studies?

Aauuu!

The generous sponsors are, of course, somewhat lacking at this moment in time. This is a problem noted by Gavrilov at greater length in an article at the Longevity Meme. Why longevity research funding is hard to come by is explained in an excellent piece by biogerontologist Aubrey de Grey - there is a problematic feedback loop between scientific conservatism, funding sources and public opinion. The normal process of organization, paradigm shift and debate within the scientific community is proceeding at a slow pace, but scientists also face obstacles arising from a lack of public awareness, widespread misconceptions and poor education. Research advocates and their projects (like the M Prize) can help to make the jobs of scientists like Leonid Gavrilov and Aubrey de Grey a great deal easier by raising awareness and increasing understanding of healthy life extension research - thus making funding much more likely.

NYT On Alcor

The New York Times is running an educational article on Alcor, the largest and most well known cryonics provider. "Alcor is a small nonprofit company built on the spectacular wager that it can rescue its patients from natural post-mortem deterioration until a distant time when cellular regeneration, nanotechnology, cloning or some other science can restart their lives, as if the diseases, heart attacks, old age, murders or accidents that concluded their first go-rounds had never happened." It's good to see the cryonics industry getting respectful, serious press; as the article notes, "Alcor knows that the rest of its potential market - that is, almost everyone else - needs an education."

Link: http://www.nytimes.com/2005/02/13/business/yourmoney/13freeze.html?pagewanted=all

An Interview With Ray Kurzweil

Dateline Alabama is carrying an interesting interview with Ray Kurzweil and a few of his detractors on the topics of longevity, science and biological immortality. I see Kurzweil's projected timelines as unrealistic, but only because a full-press multi-billion-dollar level of funding for basic research and the required technologies is not yet underway. It's going to take a while to ramp up to that level - requiring widespread public understanding and support - which is why continuing advocacy and education for serious anti-aging research is so important. The future doesn't make itself; it is a result of all our actions. If we just sit back and expect healthy life extension to happen, then we are going to be disappointed. So make yourself heard and help to support serious anti-aging research!

Link: http://www.tuscaloosanews.com/apps/pbcs.dll/article?AID=/20050212/APN/502120702&cachetime=3&template=dateline

The Pace Of Future Progress

An alternative to the prosaic debate over longevity and social security can be found at the LEF News. "We stand on the cusp of a bold new era in the history of our species in which we will see the end of death, disease and sorrow. ... According to anti-aging researcher Aubrey de Grey, in the next decade, we will be adding more than one year to our life expectancies every year, effectively keeping the cold hand of death at bay. [He] also predicts that we will be able to stop aging in mice in the next 10 years and will have human therapies to stop, even reverse, aging as little as five to 10 years after that. This makes the prospect of clinical immortality (the ability to stop aging and disease) something members of our generation should put considerable effort into." These are predictions that could happen with the right level of funding - but the funding isn't there yet.

Link: http://www.lef.org/news/LefDailyNews.htm?NewsID=1818&Section=AGING

Another Good Aubrey de Grey Interview

The busy bees of the Methuselah Foundation are doing a great job in generating press for Aubrey de Grey's presentation on the 15th. It just goes to show what can be done when you put your mind to it - excellent practice for engaging the larger players in the media. Another good interview has shown up in the University of Alberta's ExpressNews paper:

De Grey does admit his timeframe may be "somewhat overoptimistic." But he argues that only by treating it as a realistic goal do we stand any chance of making it happen. The main obstacle to progress, he said, is that many biologists work on the problems of aging in isolated experimental silos, too rarely pulling back from their work to take the long view.

"You don't have departments of theoretical biology, but you ought to," said de Grey. "When I actually identify a way in which different strands of biology could be put together for a productive purpose, I find it quite easy to get people interested in listening to each other once they've heard about the possibility."

The question de Grey faces perhaps more than any other, however, has less to do with cell biology than ethics or social science - is it desirable to extend human life, given that our world is already overpopulated? For de Grey, it's not up to him, or even any of us, to make that call. It is, however, a fundamental right of future societies to decide whether to adopt anti-aging therapies once discovered and whether the accompanying sacrifices are worth it.

"There are good reasons to suppose that we may genuinely have to make hard choices as a society," he said. "I like to be quite stark about this ... There's a good chance that we will end up having to make a choice between having fewer children than we really want or living less time than we really want.

"This is a choice that society of the future is entitled to make for itself as opposed to us trying to second guess ... by not developing these things and thereby forcing on society the requirement to choose death rather than childlessness."

A number of important talking points are buried in that short except. Firstly on timescales: if everyone accepts that developing working anti-aging medicine is going to take a long time - absent the work done to confirm this proposition - then this research will certainly take a long time. This is because funding will lag; no funding group devotes much time and money to what are considered to be extremely long term projects. Thus pessimism, reasonable or unreasonable, becomes a self-fulfilling prophecy in scientific and medical progress. Aubrey de Grey has good science and good motivations behind his timescale claims; in order to have any chance of reaching the goal of greatly extended healthy life spans in our lifetime, we need to support this research.

On overpopulation, I'm of the view that it's a nonissue based on what we know of human behavior and economics; Max More treats this subject well in his essay on Superlongevity and Overpopulation. Nor is the world currently overpopulated. Too many people mistake the terrible problems caused by politically-maintained poverty for overpopulation, but this is not a case of too many people - rather, it is an absence of the rule of law and undercapitalization of existing, unused resources. Here, as in many other aspects of healthy life extension and related topics, we need a better, more effective approach to education and the presentation of our ideas.

Life Span Increase Projection From Systems Biology

An e-mail from the Gerontology Research Group references an interesting projection from Leroy Hood of the Institute for Systems Biology:

One of our GRG Co-Founders, Dr. Robert Nathan, asked Dr. Hood during the Q&A Session that followed his lecture this afternoon at CalTech (attended by Prof. David Baltimore, CalTech President), "But what about aging, which you hardly mentioned in your talk? Shouldn't that receive some special focus of attention in the new Systems Biology?"

Hood replied: "We've made some spectacular progress in aging research using model organisms like C. elegans and Drosphila. Next, we have to apply this knowledge to humans. I predict that, by applying the principles of Systems Biology, in ten years we can expect to see a 10- to 20-year increase in average life expectancy for the general population. In ten years, with the cost of DNA sequencing coming down by another 100,000-fold due to advances in technology, every single person in this room, who wishes, will have their unique DNA sequence routinely placed in a computer data base that will lead to custom therapeutic interventions that are tailored to their individual, idiosyncratic genes."

The point regarding cost reductions is one that is frequently made by Randall Parker. I see advances in life span of the sort projected by Leroy Hood as incidental life extension - not arising due to deliberate efforts to extend the healthy human life span, but rather due to increased capabilities in medical interventions across the board. According to the reliability theory of aging, the more cellular wear and damage you prevent throughout your lifetime, the longer you will live. Incidental life extension isn't a bad thing, but directed, serious anti-aging research is needed in order to reach escape velocity - in which healthy life span increases faster than we age - in our lifetimes.

Type 2 Diabetes Progress

It is good to see that the most common age-related conditions yielding their secrets to scientists. EurekAlert reports: "Using a revolutionary technique to turn off chemical signals inside the cell, scientists at Joslin Diabetes Center have discovered that the different metabolic abnormalities present in type 2 diabetes can be caused by knocking out two key signals in liver cells. Their findings in mice may someday lead to strategies in humans to boost these two different signals, providing a powerful new way to treat the different metabolic components present in the most common form of diabetes." As we have seen in recent years, understanding the molecular biochemistry of a condition provides a fairly short path to developing effective therapies.

Link: http://www.eurekalert.org/pub_releases/2005-02/jdc-jss021005.php

Another Aubrey de Grey Interview

Vue Weekly interviews biogerontologist Aubrey de Grey: "He proposes that the development of 'rejuvenation therapies' to ward off aging in humans could happen within about 30 to 100 years. 'The only thing that might change that [timescale] is if over the next 10 years from now, the funding is good enough,' de Grey says. This period will be critical, he explains, as he predicts that within this span of time scientists will dramatically improve the longevity of mice. ... 'I think that sort of result [in mice] will be enough to convince society that we can actually do something about aging in humans fairly soon,' he argues, 'and that will change everything.'" Extremely long lived mice will make funding for human radical life extension that much more likely - hence the Methuselah Mouse Prize.

Link: http://www.vueweekly.com/articles/default.aspx?i=1543

Debating SENS

Jay Fox comments on debates over SENS (Strategies for Engineered Negligible Senescence) within the healthy life extension community.

The important thing to keep in mind is that, in debating how "good" an anti-aging treatment is, we only need to consider whether it will allow people to live long enough for something better to come along. In other words, the first effective anti-aging treatments don't need to completely cure aging, they just need to buy us time for something better.

In that light, Dr. de Grey has admitted that his 7-point strategy is likely not going to be a true cure for aging. It's not good enough to cure aging, but he believes it will be good enough to buy us time, so much time that future advances will continue to buy us more time, etc. In effect, once his 7-point plan is achieved, future biomedicine will always stay at least one step ahead of the aging process. This is what Dr. de Grey means when he says "escape velocity".

I do not doubt that Dr. de Grey's plan will work, and so it may be perceived as somewhat hypocritical that I am sometimes critical of Dr. de Grey's plan. What needs to be made clear is that I don't doubt that Dr. de Grey's plan will work; what I have reservations about is whether it will be available soon enough, and broadly enough, to save the most lives possible. That is, I believe that there are other strategies which will make escape velocity occur sooner, for more people, and in effect, save more lives.

My position on these sorts of discussions is that we are still in the stage of needing many more qualified and useful people (e.g. scientists, folks with money to spend on research, advocates with a large audience, etc) to take part. It's never too early to critique and improve ideas - especially when it comes to getting to the end goal more rapidly - but we still need to devote much more effort to raise awareness and bring new faces to the debating table.

Aubrey de Grey In Alberta

As biogerontologist Aubrey de Grey's presentation at the University of Alberta grows near, the Gateway is running an overview of his views on the future of aging and rejuvenation research. "He has theorized that aging in humans is caused by molecular and cellular damage that accumulates in the body over time (the by-products of basic processes like digestion). By limiting the buildup of these by-products, which are only harmful to the body in high quantities, de Grey suspects people can thwart the aging process and live young, vibrant lives for thousands of years. Currently, scientists are working to find ways of making mice live far beyond their typical life expectancies. To speed up the process, de Grey helped establish [the Methuselah Mouse Prize], a cash award given to scientists who can engineer the oldest mice."

Link: http://www.gateway.ualberta.ca/view.php?aid=3961

Committee Fights Anti-Research Legislation

ABCNews reports that the committee behind Proposition 71 is gearing up to fight federal legislation that would criminalize embryonic stem cell research into cures for age-related conditions. "Robert Klein II, the wealthy Palo Alto housing developer who chaired the campaign, said the organization intends to raise $1 million to fight Sen. Sam Brownback, R-Kansas, and his anti-cloning allies in the Senate. ... Brownback is sponsoring legislation that would ban the cloning of human embryos for any reason, including medical research. Such a law would directly threaten the California Institute for Regenerative Medicine, which intends to use some of the $3 billion in voter-approved bond money to dole out grants for so-called therapeutic cloning projects."

Link: http://abcnews.go.com/Technology/wireStory?id=486214

Gene Therapy For Parkinson's

(From News-Medical.net). Researchers are getting closer to demonstrating a gene therapy for Parkinson's disease: "Parkinson's disease is caused by the death of brain cells that produce a vital chemical known as dopamine, which carries messages that tell the body how and when to move. In tests with 31 monkeys, including a control group, scientists inserted copies of a gene to produce [the protective protein] GDNF into a region in the front part of the brain called the striatum. They then induced Parkinson-like conditions by introducing a drug to destroy the dopamine-producing cells. Seventeen weeks after that, not only did the GDNF-treated monkeys show improvement in performing tasks, analysis of brain tissue showed the animals' dopamine systems were actually spared by the treatment."

Link: http://www.news-medical.net/?id=7686

On State Funded Stem Cell Research

MSNBC is running an overview article on current funding initiatives for stem cell research in US state legislatures. "Everyone's rushing to put together a stem cell program. People recognize that this field of study has incredible potential, not only to cure disease, but also as an economic tool." A big change from just a few years ago, when politicians were racing to ban this most promising field of research. Private funding is making a comeback in this less restrictive atmosphere: "Proposition 71 has caused a stir of enthusiasm in the biotechnology community and has stoked investor interest in the science. ... Over the last eight years, Geron has invested $96 million in the field of human embryonic stem cell research."

Link: http://www.msnbc.msn.com/id/6847933/

Aubrey de Grey Interviewed For Wired

A brief interview with biogerontologist Aubrey de Grey can be found in the February issue of Wired magazine:

WIRED: Your Gerontology piece claims that the current approach to prolonging life - developing drugs that mimic nutrient deprivation - is wrong. How so?

DE GREY: I present a detailed evolutionary argument that caloric restriction in humans will give only a very small increase in lifespan. Starved worms and flies can live many times longer than normal, whereas mice can live only about 40 percent longer and dogs only 10 to 15 percent. We'll get only two to three years from that approach. Better than nothing, but not enough. This is a big deal because the majority of academic-led biotech startups aimed at postponing aging are developing drugs based on caloric restriction.

WIRED: You think we can actually reverse aging instead of just slow it down?

DE GREY: That's right. The rejuvenation therapies we are on the verge of developing will actually repair cellular damage. The reason I think we're close is that we can describe what aging is in such minute detail, and we can also describe feasible, foreseeable ways of repairing each of those categories of damage that go together to make up aging.

You can read Aubrey de Grey's work in detail at the Strategies for Engineered Negligible Senescence website, and you can help to make his view of the future of rejuvenation research a reality by contributing to the Methuselah Mouse Prize fund.

Once More Into the Breach

As noted recently by a number of commentators, the State of the Union address suggests that efforts to criminalize therapeutic cloning and embryonic stem cell research in the US will continue.

Sen. Sam Brownback (R-Kansas) and Rep. Dave Weldon (R-Florida) have been trying to push their anti-human-cloning bills through Congress since 2001, with Bush's unofficial stamp of approval. If either bill becomes law, researchers who violate the law would face up to $1 million in fines and jail time. Such a law could also put a kink in California's stem-cell initiative, which dedicates $3 billion to stem-cell research over the next decade, and could cause problems for similar efforts in New Jersey, Maryland, Wisconsin and several other states.

"I think what we have here is a real civil war over stem cells, and if the president has his way with this policy and we see the Brownback bill passes, it's going to undercut every single state funding initiative for stem-cell research,"

...

"I would expect to see the Weldon and Brownback bills reintroduced soon. ... What's interesting about the president's statement is that he goes further than Brownback in seeking a ban on all embryo creation for research, whether through (somatic cell nuclear transfer) or in vitro techniques, and states his intention to work with Congress to get this into law."

Federal criminalization of this science will wreck important research into cures for age-related conditions - diabetes, Parkinson's, Alzheimer's, cancer, and many more - and block a greater understanding of biochemical processes. It will drive away the billions in private funding still waiting in the wings. So much damage has been done and time wasted already - hundreds of thousands of people continue to suffer and die each and every day.

It is a good idea to make our opinions known before this goes much further. A sample letter to your elected representatives can be found at the Longevity Meme; I strongly urge to take it as a basis for your own letter. You can find fax information for your representatives at Congress.org - a fax is much more likely to be read than any other form of communication with politicians in the US.

More On Federal Research Ban

Wired has more on the continuing threat of a federal ban on all therapeutic cloning - a technology vital to the most promising regenerative research. "I would expect to see the Weldon and Brownback bills reintroduced soon. What's interesting about the president's statement is that he goes further than Brownback in seeking a ban on all embryo creation for research, whether through (somatic cell nuclear transfer) or in vitro techniques, and states his intention to work with Congress to get this into law ... The real risk is having the substance of the Brownback bill tacked on as a non-germane amendment to some other Senate legislation." We must make our voices heard once more as anti-research groups continue to try to block cures and cause suffering.

Link: http://www.wired.com/news/medtech/0,1286,66533,00.html?tw=wn_tophead_3

Telomere Tales

An good introductory article on telomeres showed up this week at SAGE Crossroads. "For a long time scientists believed [that] the length of our lives was meted out in our telomeres - the protective caps at the ends of the threadlike chromosomes that carry our genes. But life is never as simple as legend, and most researchers have abandoned the telomere theory of aging. They haven't given up on telomeres, though. Scientists are now testing whether degradation of these termini heralds the maladies associated with growing old, such as heart disease, dementia, and cancer. Understanding the association between telomeres and disease could lead to better treatments for cancer or new ways to stay healthy as we mature."

Link: http://www.sagecrossroads.net/public/news/show_article.cfm?articleID=99

A4M Leaning Towards Regenerative Medicine

This should be of interest for those who like to keep tabs on what the anti-aging marketplace is up to: if you cast your eyes over the A4M website, you'll note a strong focus on the growing field of regenerative medicine these days. A4M are influential in the sense that they both reflect and help determine marketing and presentation within the anti-aging industry - reputable and disreputable groups included. Regular readers will recall that I have my issues with the way in which A4M conducts business, especially as it relates to their conferences, but a strong focus on regenerative medicine from this crowd can't be a bad thing. I don't think they have the clout to hurt the public view of regenerative medicine in any way at this time, and a greater influx of real, working science may chase out some of the bad actors in the industry. This has been coming for a while; the last update to the A4M definition of "anti-aging medicine" incorporated language that would not sound out of place in a prospectus for future regenerative medicine.

To this challenge, anti-aging medicine arrives as the new health care paradigm, offering a solution to alleviate some of the burden of this burgeoning older population. Anti-aging medicine, an extension of preventive health care, is the next great model of health care for the new millennium. This model is based on the early detection, prevention, and reversal of aging- related diseases.

One sea change I hope to see in this marketplace is good medicine chasing out bad medicine - if real, demonstrable therapies for age-related conditions exist, then the modern pill and potion salesmen have less of a leg to stand on. Good riddance to them, since their actions greatly damage the credibility of serious research into slowing or reversing the aging process itself.

As a last note, please do read my commentary on anti-aging medicine and science at the Longevity Meme before taking anything you read at A4M or related sites at face value.

Read The Newsletter!

It's time for one of our occasional, gentle reminders that the Longevity Meme offers an e-mail newsletter. The Longevity Meme Newsletter contains news, opinions and commentary for people interested in making use of diet, lifestyle choices, technology and proven medical advances to live longer, healthier lives - which is why we are all here, right? If you don't feel like visiting the website for daily updates, you can sign up to receive a weekly e-mail summary of all of our news as well as a mixed bag of commentary, thoughts and updates from the healthy life extension community. You should take a look at the latest newsletter and see what you think.

Link: http://www.longevitymeme.org/newsletter/

Yet More Differentiation Progress

Resources are pouring into the vital task of understanding - and eventually controlling - the biochemistry and genetics of stem cell differentiation. Here, ScienceDaily reports on advances relating to blood stem cells: "Blood cell formation, known as hematopoiesis, begins with a [stem cell], which can either 'self-renew' and make more copies of itself or differentiate into either red blood cells, various types of white blood cells, or platelets. The genes that control proliferation and differentiation have been difficult to study using traditional gene disruption methods because loss of genes thought to be critical for this process often results in embryonic death, making it impossible to study the role of the gene of interest in mature animals. [Scientists have] found a way around this problem."

Link: http://www.sciencedaily.com/releases/2005/02/050201193549.htm

Superlongevity Without Overpopulation

The latest Longevity Meme article, by Max More of the Extropy Institute, addresses common Malthusian concerns about overpopulation in a world of greatly extended human life spans. Simply put, fears of overpopulation are no more than fears - and Max More handily shows why this is the case. As he says, "We would be severely misguided not to push for extended life out of fear of overpopulation. Let us move full speed ahead with extending life span." This article is one of many excellent pieces that can be found in The Scientific Conquest of Death: Essays on Infinite Lifespans, a book published by the Immortality Institute.

Link: http://www.longevitymeme.org/articles/viewarticle.cfm?page=1&article_id=24

Private Stem Cell Funding Returning?

It's good to see any sign of private philanthropic funding for embryonic stem cell research. Up until very recently, the strong possibility of criminalization of this research had scared away all but the hardiest funding organizations. "Inadequate federal funding for human embryonic stem cell research gives private funding in this area an exceptionally high impact, and we are very grateful for the investment that [the W.M. Keck Foundation] is making here. ... This grant unites expertise in engineering, bioinformatics and stem cell biology in a way that is unprecedented, and it provides a glimpse of the future of biological research." This is important work - finding out exactly how embryonic stem cells differentiate and how to control this process.

Link: http://www.news.wisc.edu/10654.html

Superlongevity Without Overpopulation

The Scientific Conquest of Death: Essays on Infinite Lifespans, a book published by the Immortality Institute, examines many of the social as well as technological aspects of the future of healthy life extension. Max More's contribution to The Scientific Conquest of Death, reprinted here with permission, handily demonstrates that fear of overpopulation is not a legitimate objection to greatly extending the healthy human life span.

Copyright © Max More.

Proponents of superlongevity (indefinitely extended life spans) have been making their case for the possibility and desirability of this change in the human condition for decades. For just as long, those hearing the arguments for superlongevity have deployed two or three unchanging, unrelenting responses. The question: "But what would we do with all that time?" is one of them. Another is the "But death is natural!" gambit. The final predict-able response is to conjure up the specter of overpopulation. Despite strong downward trends in population growth since this issue gained visibility in the 1960's, the third concern remains an impediment.

Paul Ehrlich's 1968 bestseller, The Population Bomb [1], ignited a trend in which alarmists routinely ignored data and reasonable projections to scare the public. Those of us who see achieving the indefinite extension of the human life span as a central goal naturally find this behavior quite irritating. If baseless fear wins out, we will gain little from our personal programs of exercise, nutrition, or supplementation. Widespread fear leads to restrictive legislation - legislation that in this case could be deadly. Although the volume has been turned down a little on the population issue, it continues to reverberate and deserves a response. The purpose of this essay is to address the essential concerns, provide current facts, and dispel the errors behind the overpopulation worries.

VALUES FIRST

As I will show, we have little reason to fear population growth with or without extended lives. However, to bring into focus an ethical issue, I will pretend for a moment that population growth is or will become a serious problem. Would this give us a strong reason for turning against the extension of human lifespan?

No. Opposing extended life because, eventually, it might add to existing problems would be an ethically irresponsible response. Suppose you are a doctor faced with a child suffering from pneumonia. Would you refuse to cure the child because she would then be well enough to run around and step on the toes of others? On the contrary, our responsibility lies in striving to live long and vitally while helping others do the same. Once we are at work on this primary goal, we can focus more energy on solving other challenges. Long, vital living at the individual level certainly benefits from a healthy physical and social environment. The superlongevity advocate would want to help find solutions to any population issues. But dying is not a responsible or healthy way to solve anything.

Besides, if we take seriously the idea of limiting life span so as to control population, why not be more proactive about it? Why not drastically reduce access to currently commonplace medical treatments? Why not execute anyone reaching the age of seventy? Once the collective goal of population growth is accepted as overriding individual choices, it would seem hard to resist this logic.

IT IS HOW MANY, NOT HOW LONG, THAT MATTERS?

Limiting population growth by opposing life extension not only fails the ethical test, it also fails the pragmatic test. Keeping the death rate up simply is not an effective way of slowing popula-tion growth. Population growth depends far more on how many children families have, as opposed to how long people live. In mathematical terms, longer life has no effect on the exponential growth rate. It only affects a constant of the equation. This means that it matters little how long we live after we have reproduced. Compare two societies: In country A, people live on average only to 40 years of age, each family producing 5 children. In country B, the life span is 90 years but couples have 4 children. Despite the much longer life span in country B, their population growth rate will be much lower than that of country A. It makes little difference over the long term how many years people live after they have had children. The population growth rate is determined by how many children we have, not how long we live.

Even the short-term upward effect on population due to a falling death rate may be cancelled by a delay in child bearing. Many women in developed countries choose to bear children by their early 30's because the obstacles to successful pregnancy grow as they age. As the last few decades have already shown, extending the fertile period of women's lives would allow them to put off having children until later, until they have developed their careers. Not only will couples have children later, we can expect them to be better positioned financially and psychologically to care for them.

Almost certainly, the first truly effective technologies to extend the maximum human life span will come with a significant cost of human development and application. As a consequence population effects would first be felt in the developed countries. This points to another flaw in the suggestion that extended longevity will dramatically boost population growth. The fact is, superlongevity in the developed nations would have practically no global or local population impact. The lack of global impact is a consequence of the small and falling share of the global population accounted for by the developed nations. No local population boom drama can realistically be expected because these countries are experiencing very low, zero, or negative population growth:

The share of the global population accounted for by the developed nations has fallen from 32 percent in 1950 to 20 percent currently and is projected to fall to 13 percent in 2050. [2] If we look just at Europe, we see an even more remarkable shrinkage: In 1950, Europe accounted for 22 percent of the global population. Currently it has fallen to 13 percent, and is projected to fall to 7 percent by 2050. [3] To put this in perspective, consider that the population of Africa at 749 million is now greater than that of Europe at 729 million, according to UN figures. Europe's population growth rate of just 0.03 per cent will ensure that it will rapidly shrink relative to Africa and other developing areas.

In Eastern Europe, population is now shrinking at a rate of 0.2 percent. Between now and 2050, the population of the more developed regions is expected to change little. Projections show that by mid-century, the populations of 39 countries will be smaller than today. Some examples: Japan and Germany 14 percent smaller; Italy and Hungary 25 percent smaller; and the Russian Federation, Georgia and Ukraine between 28-40 percent smaller. [3]

For the United States (whose population grows faster than Europe), the bottom line was summed in a presentation to the President's Council on Bioethics by S.J. Olshansky who "did some basic calculations to demonstrate what would happen if we achieved immortality today". The bottom line is that if we achieved immortality today, the growth rate of the population would be less than what we observed during the post World War II baby boom. [4]

Low fertility means that population trends in the developed regions of the world would look even milder if not for immigra-tion. As the 2000 Revision to the UN Population Division's projections says: "The more developed regions are expected to continue being net receivers of international migrants, with an average gain of about 2 million per year over the next 50 years. Without migration, the population of more developed regions as a whole would start declining in 2003 rather than in 2025, and by 2050 it would be 126 million less than the 1.18 billion projected under the assumption of continued migration."

All things considered, countries fortunate enough to develop and make available radical solutions to aging and death need not worry about becoming overpopulated. In an ideal scenario, life extension treatments would rapidly plunge in cost, making them affordable well beyond the richest nations. We should therefore look beyond the developed nations and examine global popula-tion trends in case a significantly different picture emerges.

GLOBAL POPULATION FLATLINING

We have seen that we have no reason to hesitate in prolonging life even if population were to grow faster due to higher fertility rates. But does the developing world, with or without cheap, ubiquitous life extension, have much to fear from a population explosion? Are populations growing out of control in those regions? The fad for popular books foretelling doom started in the 1960's, at the tail end of the most rapid increase in population in human history. Since then, the poorer countries, well below us in the development cycle, have also been experiencing a drastic reduction of population growth. This is true despite major relative life extension - the extra decades of life bestowed by medical intervention and nutrition.

Taking a global perspective, the numbers reveal that the average annual population growth rate peaked in 1965-1970 at 2.07 percent. Ever since then, the rate of increase has been declining, coming down to 1.2 per cent annually. That means the addition of 77 million people per year, based on an estimated world population of 6.1 billion in mid-2000. [3] A mere six countries account for fully half of this growth: India for 21 percent; China for 12 percent; Pakistan for 5 percent; Nigeria for 4 percent; Bangladesh for 4 percent, and Indonesia for 3 percent. China has markedly reduced the average number of births per woman over the last 50 years from six to 1.8. Starting from the same birth rate at that time, India has fallen much less, although still almost halving the rate to 3.23 percent. If these trends continue up to 2050, India's population will exceed that of China. [5]

Despite the fecundity of these top people-producers, the overall picture is an encouraging one:

The total fertility rate for the world as a whole dropped by nearly two-fifths between 1950/55 and 1990/95 - from about 5 children per woman down to about 3.1 children per woman. Average fertility in the more developed regions fell from 2.8 to 1.7 children per woman, well below biological replacement. Meanwhile total fertility rates in less developed nations fell by 40 percent, falling from 6.2 to 3.5 children per woman. [6]

We can expect population growth to continue slowing until it reaches a stable size. What size will that be? No one knows for sure, but the best UN numbers indicate that population may peak at as low as 8 billion people, with a medium projection of 9.3 billion and an upper limit projection of 10.9 billion. [2;7] The medium projection also points to global population peaking around 2040 and then starting to fall.

I wrote the first version of this paper in 1996. In revising it, I found it interesting that, less than a decade ago, the higher projection allowed for 12 billion or more. Demographers had continued their long tradition of over-estimating population growth. This effect seems to have been reduced, but take all projections (especially those longer than a generation) with a healthy dose of skepticism.

FORCES OF POPULATION DECELERATION

Why, though, should we expect people in less developed countries, even given contraceptives, to continue choosing to have smaller families? This expectation is not merely speculation based on recent trends. Sound economic reasoning explains the continuing trend, and makes sense of why the poorer nations are only just beginning to make the transition to fewer births.

Decelerating population growth appears to be an inevitable result of growing wealth. Early on in a country's developmental curve, children can be regarded as 'producer goods' (as economists would say). Parents put their children to work on the farm to generate food and revenue. Very little effort is put into caring for the child: no expensive health plans, special classes, trips to Disneyland, X-Men action figures, or mounting phone bills. As we become wealthier, children become 'consumer goods'. That is, we look on them more and more as little people to be enjoyed and pampered and educated, not beasts of burden to help keep the family alive. We spend thousands of dollars on children to keep them healthy, entertain them, and educate them. We come to prefer fewer children to a vast mob of little ones. This preference seems to be reinforced by changing tastes resulting from improved education. The revenue vs. expense equation for extra children further shifts toward having fewer offspring as populations become urbanized. Children cost more to raise in cities and can produce less income than in the country.

Fertility declines for another reason: As poorer countries become wealthier, child mortality falls as a result of improved nutrition, sanitation, and health care. Reduced child mortality in modern times can come about even without a rise in income. People in poorer countries are not stupid; they adjust their childbearing plans to reflect changing conditions. When child death rates are high, research has shown that families have more children to ensure achieving a given family size. They have more children to make up for deaths, and often have additional children in anticipation of later deaths. Families reduce fertility as they realize that fewer births are needed to reach a desired family size. Given the incentives to have fewer children as wealth grows and urbanization proceeds, reduced mortality leads to families choosing to reduce family size.

Economic policy helps shape childbearing incentives. Many of the same people who have decried population growth have supported policies guaranteed to boost childbirths. More than that, they boost childbearing among those least able to raise and educate children well. If we want to encourage people to have more children, we should make it cheaper for them to do so. If we want to discourage fertility, or at least refrain from pushing it up, we should stop subsidizing it. Subsidies include free education (free to the parents, not to the tax-payers), free child health care, and additional welfare payments to women for each child they bear. If parents must personally bear the costs of having children, rather than everyone else paying, people will tend to have just the number of children for whom they can assume financial responsibility.

Even if there were a population problem in a few countries, extending the human life span would worsen the problem no more than would improving automobile safety or worker safety, or reducing violent crime. Who would want to keep these deadly threats high in order to combat population growth? If we want to slow population growth, we should focus on reducing births, not on raising or maintaining deaths. If we want to reduce births, we might voluntarily fund programs to provide contraceptives and family planning to couples in poorer countries. This will aid the natural developmental process of choosing to have fewer children. Couples will be able to have children by choice, not by accident. Women should also be encouraged to join the modern world by gaining the ability to pursue vocations other than child-raising.

'OVERPOPULATION' DISTRACTS FROM REAL PROBLEMS

Major downward revisions in population growth - throughout the UN's sixteen rounds of global demographic estimates and projections since 1950 - have drained the plausibility of any overpopulation-based argument against life extension. We can better understand the real problems that are talked about in relation to overpopulation instead as issues of poverty. Poverty, in turn, results not from having too many people, but from several major factors including political misrule, continual warfare, and insecurity of property rights.

As Bjorn Lomborg points out, we find many of the most densely populated countries in Europe. The region with the highest population density, Southeast Asia, has about same number of people per square mile as the United Kingdom. Although India has a large, growing population, it also has a population density far lower than that of The Netherlands, Belgium, or Japan. Lomborg also notes that Ohio and Denmark are more densely populated than Indonesia. [3]

We should also recognize that most population growth takes place in urban areas, which provide a better standard of living. As a result, most of this planet's landmass will not be more densely populated than it is today. Over the next three decades, we can expect to see almost no change in the rural population of the world and, by 2025, 97% of Europe will be less densely populated than today. [8] We should celebrate the urbanization trend since even the urban poor thrive better than they would in the country. The causes of this include better water supplies, sewage systems, health services, education, and nutrition. [9] Oddly enough, serious infectious diseases like malaria are less threatening the closer buildings are together (and so the smaller the space for swampy areas beloved of mosquitoes and flies). [10]

SUSTAINABILITY AND THE GREAT RESTORATION

The future could be far brighter than the eco-doomsters have long portrayed it. As Ronald Bailey [11] reports:

Jesse Ausubel, director of the Program for the Human Envi-ronment at Rockefeller University, believes the 21st century will see the beginning of a 'Great Restoration' as humanity's productive activities increasingly withdraw from the natural world.

If world farmers come to match the typical yield of today's US corn growers, ten billion people could eat amply while requiring only half of today's cropland. This is one way in which technological advance in farming will allow vast expanses of land to revert to nature. Transgenic crops could also multiply today's production levels while solving several significant environmental challenges. [12]

Visions that emphasize human ingenuity and opportunity have a far more impressive historical record than those that emphasize human passivity and helplessness. Paul Ehrlich is a classic case of the latter type and you have only to browse his dark, alarming books to recognize how consistently bad he has been at making environmental predictions. In a 1969 article, Ehrlich predicted the oceans dead from DDT poisoning by 1979 and devoid of fish; 200,000 deaths from 'smog disasters' in New York and Los Angeles in 1973; U.S. life expectancy dropping to 42 years by 1980 because of pesticide-induced cancers, and U.S. population declining to 22.6 million by 1999. [13] Ehrlich famously lost a ten year bet against cornucopian economist Julian Simon (and refused to renew the bet). In 1974, Ehrlich recommended stockpiling cans of tuna due to the certainty of protein shortages in the USA. And so on.

As Bailey explains [13], contrary to Ehrlich:

Instead, according to the United Nations, agricultural produc-tion in the developing world has increased by 52 percent per person since 1961. The daily food intake in poor countries has increased from 1,932 calories, barely enough for survival, in 1961 to 2,650 calories in 1998, and is expected to rise to 3,020 by 2030. Likewise, the proportion of people in developing countries who are starving has dropped from 45 percent in 1949 to 18 percent today, and is expected to decline even further to 12 percent in 2010 and just 6 percent in 2030. Food, in other words, is becoming not scarcer but ever more abundant. This is reflected in its price. Since 1800 food prices have decreased by more than 90 percent, and in 2000, according to the World Bank, prices were "lower than ever before".

A reading of economic and social history quickly makes one thing plain: throughout history people have envisaged overpopulation. Even the great nineteenth century social scientist W. Stanley Jevons in 1865 claimed that England's industrial expansion would soon cease due to the exhaustion of the country's coal supply. [15] However, as shortages developed, prices rose. The profit motive stimulated entrepreneurs to find new sources, to develop better technology for finding and extracting coal, and to transport it to where it was needed. The crisis never happened. Today, the USA has proven reserves sufficient to last hundreds or thousands of years. [16] If one resource does begin to run low, rising prices will encourage a switch to alternatives. Even a vastly bloated population cannot hope to exhaust energy supplies. (Solar energy and power from nuclear fission and soon fusion are practically endless.) So long as we have plentiful energy we can produce substitute resources and even generate more of existing resources, including food. Even if population were to grow far outside today's highest projections, we can expect human intelligence and technology to comfortably handle the numbers.

Human intelligence, new technology, and a market economy will allow this planet to support many times the current population of 6.2 billion - it can support many more humans than we are likely to see, given trends toward lower birth rates. Many countries, including the USA, have a rather low population density. If the USA's population were as dense as Japan - hardly a crowded place overall - our population would be 3.5 billion rather than 265 million. If the USA had a population density equal to that of Singapore, we would find almost 35 billion people here, or almost seven times the current world population. New technolo-gies, from simple improvements in irrigation and management to current breakthroughs in genetic engineering should continue to improve world food output. Fewer people are starving despite higher populations. This does not mean they are feeling satisfied. Millions still go hungry or are vulnerable to disruptions in supply. We need to push to remove trade barriers, abolish price controls on agriculture (which discourage production and investment), and pressure governments engaging in warfare and collectivization to change their ways.

POLLUTION

Nor should we expect pollution to worsen as population grows. Contrary to popular belief, overall pollution in the more developed countries has been decreasing for decades. In the USA, levels of lead have dropped dramatically. Since the 1960's levels of sulfur dioxide, carbon monoxide, ozone, and organic compounds have fallen despite a growing population. Air quality in major urban areas continues to improve, and the Great Lakes are returning toward earlier levels of purity. [17] This is no accident. As we become wealthier, we have more money to spare for a cleaner environment. When you are longing for food, shelter, and other basics, you will not spare much thought for the environment. So long as mechanisms exist for converting desires for cleaner air and water and space for recreation into the things themselves, we can expect it to happen.

Most effective at spurring the positive changes are markets - price signals creating incentives for moves in the right direction. If polluters must pay for what they produce because their activity intrudes on the property rights of others, they will search for ways to make things with less pollution. Pollution problems do exist. Most of them can be traced to a failure to enforce private property rights, so that resources are treated as free goods that need not be well managed. Fishing in unowned bodies of water is an example of this. The desertification of collectively or government owned land in Africa is another. We can be reasonably confident that the trend towards less pollution with greater population will continue. However, complacency is out of place. We should press for responsible management of resources by privatizing collectively owned resources to create incentives for sound management and renewal.

So long as we continue to allow freedom to generate more wealth and better technology, we can expect pollution to continue abating. More efficient recycling, production processes that generate fewer pollutants, and better monitoring and detection of polluters, along with economic incentives making each producer responsible for their output, will allow us to continue improving our environment even as population grows. Assuming that we achieve complete control of matter at the molecular level, as expected by nanotechnologists, we will have the keys to production without pollution. Another product of molecular manufacturing will be the disappearance of most large-scale, clumsy machinery. Less and less land will need to be used for manufacturing equipment, making more room for people to enjoy. Some manufacturing will be moved into space. The result of these and other changes (some of which are already underway) will be the freeing of the Earth from unwanted, but previously necessary, means and by-products of manufacturing.

The population issue raises numerous factual, economic, and ethical concerns. I urge the interested reader to check into the sources listed in the References, especially the essays by Jesse Ausubel [18] and the books by Bailey, Lomborg, and Simon. [3;19;20-25] I have only sketched lines of thinking showing that we would be severely misguided not to push for extended life out of fear of overpopulation. Let us move full speed ahead with extending life span: Once we have vanquished aging, I would expect other threats to life, such as war and violent crime, will become even less acceptable. We can look forward to a long-lived society better off than previous generations; not only in economic well being, but also in security of life and health.

REFERENCES

1) Ehrlich, Paul R; The Population Bomb (1968); Sierra Club-Ballantine

2) World Population Prospects: The 2000 Revision (2001a); United Nations Publications

3) Lomborg, Bjorn; The Skeptical Environmentalist: Measuring the Real State of the World (2001); Cambridge University Press

4) Olshansky, SJ; "Duration of Life: Is There a Biological Warranty Period?" in: The President's Council on Bioethics (2002) Washington, DC http://www.bioethics.gov/transcripts/dec02/session2.html

5) World Population Prospects: The 2000 Revision, Additional Data (2001c); United Nations Publications

6) Eberstadt, Nicholas; "Population, Food, and Income: Global Trends in the Twentieth Century" in: Bailey (1995).

7) World Population Prospects: The 2000 Revision, Annex Tables (2001b); United Nations Publications

8) World Urbanization Prospects: The 1996 Revision (1998); United Nations Publications

9) The Progress of Nations (1997) UNICEF http://www.unicef.org/pon97/

10) Miller, Jr. Tyler G; Living in the Environment: Principles, Connections, and Solutions (1998); Wadsworth Publishing Company

11) Bailey, Ronald; "The End Is Nigh, Again" in: Reason (2002); June 26

12) Rauch, Jonathan; "Will Frankenfood Save the Planet?" in: The Atlantic Monthly (2003); October

13) Bailey, Ronald; Eco-Scam (1993); St. Martin's Press

15) Jevons S; The Coal Question: An inquiry concerning the progress of the nation and the probable exhaustion of our coal mines (1865); Kelley Publishers

16) http://www.eia.doe.gov/

17) Taylor, B et al. "Water Quality and the Great Lakes" in: Michigan's Opportunities and Challenges: Msu Faculty Perspectives, Michigan in Brief: 2002-03. Public Sector Consultants, Inc.

18) Ausubel, Jesse; "The Great Restoration of Nature: Why and How" in: Challenges of a Changing Earth (2002); pg.175-182 // Proceedings of the Global Change Open Science Conference, Amsterdam, Netherlands (2001, 10-13 July) edited by Steffen, W & Jaeger, J & Carson, DJ & Bradshaw C; Springer http://phe.rockefeller.edu/sthubert/hubert.pdf // Ausubel, Jesse; "Where is Energy Going?" in: The Industrial Physicist (2000); http://phe.rockefeller.edu/IndustrialPhysicistWhere/where.pdf

19) The True State of the Planet (1995); edited by Bailey, Ronald; The Free Press

20) Simon, Julian L; "Resources, Population, Environment: An Over-Supply of False Bad News" in: Science (1980, Vol. 280); pg.1431-1437

21) Simon, Julian L; The Ultimate Resource (1981); Princeton University Press

22) Simon, Julian L; "Forecasting the Long-Term Trend of Raw Material Availability," in: International Journal of Forecasting (1985, Vol. 1); pg.85-109.

23) Simon, Julian L; Population Matters (1990); N.J.: Transaction

24) Simon, Julian L; "Bunkrapt: The Abstractions that lead to scares about resources and population growth," in: Extropy (1993, Vol. 11); Summer/Fall 1993, pg.34-41.

25) The Resourceful Earth (1984); edited by Simon, Julian L & Kahn, Herman; Basil Blackwell, Inc.

April Smith on Changesurfer Radio

James Hughes interviewed April Smith, the new full time fundraiser for the Methuselah Foundation for his show, Changesurfer Radio. You should download the audio and give it a spin. Speaking of fundraising, April is already hard at work - so if you have good connections or a good idea to help raise the profile and funding level for the Methuselah Mouse Prize for anti-aging research, now would be a great time to speak up.

Understanding The Dauer State

Something a little more scientific from Nature for you today - a paper describing progress towards understanding dauer biochemistry. Nematode worms are known to enter the dauer state, "an enduring and non-ageing stage of the nematode life cycle with distinctive adaptive features and extended life." Cynthia Kenyon and other researchers have gained some fame through manipulation of the dauer state and related genes to greatly extend worm life span. Researchers have made good first steps here, and as these Korean scientists note, a complete understanding of duaer biochemistry "might in turn influence ageing and obesity research."

Link: http://www.nature.com/uidfinder/10.1038/nature03201

More Proposed State Research Funding

Medical News Today reports on efforts to allocate significant state funding for embryonic stem cell research in Pennsylvania. "The lawmakers are also proposing that Pennsylvania join with New Jersey and Delaware to create an interstate compact and establish a joint stem cell research center." The proposed plan appears to follow the Illinois model of a narrow tax to raise revenue for a bond issuance. "Just this week researchers in Wisconsin announced a breakthrough where stem cells taken from human embryos became motor neurons -- an experiment that might one day help scientists repair damaged nervous systems. That is the kind of research we need to support in Pennsylvania."

Link: http://www.medicalnewstoday.com/medicalnews.php?newsid=19619

Whale Longevity as an Exemplar

Here is an interesting scan of an old article on whale life span that I hadn't noticed until now (it was mentioned in an article at Lew Rockwell that touched on healthy life extension - a rather surprising sign of the way in which our ideas are spreading).

In studies that could rewrite biology textbooks and establish whales as the longest-lived mammals on Earth, scientists in Alaska and at the Scripps Institution of Oceanography in La Jolla have estimated the ages of three bowhead whales killed by Inupiat Eskimos in northern Alaska at 135 to 172 years. At the time is was killed, a fourth bowhead whale was believed to be a stunning 211 years old, the researchers concluded.

Age was estimated by looking at chemical traces in the eyes and ivory harpoon tips from a century or more ago embedded in the whales. Fascinating stuff. I've mentioned the Ageless Animals website before at the Longevity Meme; the scientific findings reported there form a good rebuttal to some objections to healthy life extension. Many of these very long-lived animals are not so different, biochemically speaking, from us humans. If animals can live such very long lives, then it's certainly within the realm of possibility to develop therapies to greatly extend human healthy life spans.

More Years Of Fighting For Research

(From the Houston Chronicle). It looks as though we are in for another four years of fighting restrictions on embryonic stem cell research and therapeutic cloning in the US. If one is to take the recent state of the union address at face value - not, generally, an advisable idea, given the obvious disconnects between most political speeches and reality - then we can expect further attempts to push through Federal bans on all such research. We can hope that the continuing threat of criminalization will have less of an effect on the vast reserves of potential private funding now that a number of states are funding this research - but this state of affairs has caused untold suffering through delays to date.

Link: http://www.chron.com/cs/CDA/ssistory.mpl/nation/3023575

The Future Of Replacement Organs

The IEEE Spectrum is running a feature on the development of biological, prosthetic and mixed ("biohybrid") replacement organs through applied regenerative medicine or simply better, smarter materials science. "Part human, part machine, replacement organs may one day extend your life ... Bob is worried about getting old. As an engineer, Bob knows that the body is just one big system that runs by chemical gradients and electrical impulses. So why is it so difficult to come up with replacement parts when bodies like his start to break down?" It certainly isn't easy; the body is a very complex machine. Beyond the required scientific advances, there are no reasons why we can't just replace body parts as they fail, however - except the brain, which is going to require better technologies for in situ repair.

Link: http://www.spectrum.ieee.org/WEBONLY/publicfeature/feb05/0205bio.html

A Fascinating Exchange (and Comments)

Preston Estep of Longenity, Inc. chose to use the Technology Review forums for the recent Aubrey de Grey cover article to comment at length on the science, inaccuracies in the article and his own views on timescales and the difficulty of developing serious anti-aging medicine. Aubrey de Grey then responded, and think the two pieces are worth a much wider audience. Unfortunately, individual posts in the TR forums can't be linked directly, so I'll reproduce the exchange here in full:

Dear Editors,

I earned my Ph.D. in George Church's lab at Harvard Medical School, a antastic breeding ground for next-generation technology research and development, and for the last few years I have been President and CEO of Longenity Inc., a Boston-area biotech company doing aging research. So it should come as no surprise that I have been an avid reader of Technology Review (TR) for many years, and that I read with particular interest your cover story on Aubrey de Grey.

Even though I have a long history as a reader I have never, until now, felt compelled to write a letter to TR.

First, I do not agree with de Grey's SENS plan; however, I do agree with certain aspects of the "life extension escape velocity" theory of human longevity (as it is referred to in the original article) -- but not with his overly-optimistic version of it, especially his estimated timeline for its occurrence. I count myself in the mainstream of scientific aging research and I think the problem of life extension is far more vexing than does Dr. de Grey.

Dr. de Grey's belief that he knows the cause of aging and completely understands the path to its control, and even reversal, is accurately summarized in the article which states "He bases his certainty that there are only seven such factors on the fact that no new factor has been discovered in some twenty years, despite the flourishing state of research in the field known as biogerontology...".

Indeed, Dr. de Grey does believe this, and he is wrong. Moreover, unlike Sherwin Nuland or other casual critics of the SENS plan -- and unacknowledged by Dr. de Grey -- mainstream scientists have produced substantial evidence not addressed by de Grey and his plan. More importantly, certain of these data are related in a way that gives the immortalist or transhumanist particular discomfort since they suggest that the SENS plan does not address the primary -- and maybe the most difficult to control -- general aspect of aging: entropy.

In plain English, the loss of order and information essential for biological function.

The general concept of biological entropy encompasses several dynamic phenomena including cellular dedifferentiation or transdifferentiation (in which normally homogeneous groups of cells of a particular type become more heterogeneous), nuclear and mitochondrial mutation, chromosomal instability, aberrant methylation and other directed modification of the genome, loss of chromatin meta-structure, or changes in other aspects of transcriptional or signaling networks that render them more noisy and less robust over time. Many recent experiments, especially large-scale microarray transcript profiles of aging, support this general concept of time-dependent decay of orderliness (for examples, see references 1, 2, and 3).

It is difficult to imagine how the information-rich order that is established during embryogenesis and development can be restored or replicated. A critical evaluation of the SENS plan shows that, except for nuclear and mitochondrial mutation and instability, this general concept is almost entirely overlooked, and in vivo order and information content are assumed to remain at a high level.

This almost certainly mistaken assumption is betrayed by the logic of the entire SENS plan, and in particular by points 1 and 3, which direct the introduction of stem cells into a new environment of a person's body where they are to -- almost magically! -- assume specific roles. Guided by what signals are they to assume these roles? By the highly orderly signaling that already exists in vivo, naturally. And herein lies the problem. We know that differentiation of stem cells into other cell types is a highly regulated process that involves factors both extrinsic and intrinsic to the cell. Extrinsic factors include direct cell-cell interactions with tissue-type specific cells, and signaling with distant cells through various small molecules, including growth factors, hormones, and neurotransmitters.

And what will be the result if -- as current evidence suggests -- that many of these cell-extrinsic signals are gradually lost, or become dysregulated, over time? Then the newly introduced stem cells probably will simply contribute additional noise to these signaling networks. So, far from fixing existing problems, this proposed solution simply exacerbates them.

Even if these extrinsic factors remain essentially unchanged during aging -- which is highly doubtful -- stem cell biology is in its infancy, as is engineering of the genome in human cells; therefore, we cannot assume that all stem cells are equal, and that their paths of differentiation are controllable or predictable. Many of the factors that likely guide and regulate cellular differentiation, genomic stability, and cellular information content likely have not yet been identified.

And we are expected to have full control of these extremely complex processes within the next twenty years? I won't say it is impossible, but I will say that we are nowhere near the engineering phase since we do not clearly understand the nature of the problem. To further complicate matters, in the past few days it has been announced that all existing embryonic stem cell lines have been contaminated by mouse feeder cells.

What unforeseen hurdle will come next?

As baffling and challenging as are de Grey's positions on aging and how to deal with it, Dr. Nuland's seem simple and pretty straightforward: if it is conventional, it is good. Dr. Nuland claims he doesn't want to live excessively long, just a really long time for a human. So, this is how he feels...for now; however, once others live beyond the current upper limit, then he'll want to do it too -- but not until then. But, then it will be fine -- desirable, even -- because others will have done it. There are several problems with this attitude; primary among them is that it gets us nowhere. What of importance would ever be accomplished if this attitude prevailed, if everyone were a follower? This is a perspective completely lacking vision and imagination.

The choice not to extend healthy and productive lifespan also implicitly grants to the young an unearned degree of respect not accorded to older and wiser people. We are trained by innate mechanisms, refined by millions of years of evolution, to think highly of the young, to aspire to their advancement and betterment, and even to sacrifice the advancement and betterment of ourselves in this cause.

But I agree with the general proposition that this behavior is subject to modification, primarily because with wisdom comes the realization that while young people have certain admirable virtues, they also are far more violent, irrational, ignorant, and mistakenly -- and sometimes even dangerously -- idealistic. A great quote by H.H. Williams highlights a significant difference between young and old, and it succinctly summarizes why I have such admiration and respect for older people:

"Furious activity is no substitute for understanding." I think that a world in which healthy and wise older folks greatly outnumbered wild and reckless younger ones would be a fine place to be.

And then there is Dr. Nuland's speculation about the killer benevolence that will bring about the end of the world. While I don't think his apocalyptic vision completely unreasonable he should be cautious about casting stones; de Grey, at least, has methodically compiled some evidence to support his theories, although, it is far from sufficient to tackle the enormity of the problem. Nevertheless, at least he is trying -- very hard, in fact -- to do something I consider to be noble and worthwhile: he is trying to advance the cause of humanity -- all of humanity -- whether or not certain individuals want any part of it.

But he cannot succeed if he continues to pretend that his fellow scientists disagree with his theories out of ignorance. Nobody, not even de Grey, is above the normal scientific exchange in which unpleasant or unanticipated facts must be accounted for by either disproof, or by modification of existing theory, not by ad hominem dismissals of the messengers as being too "ignorant" to understand his brave and advanced conjectures. Methinks he doth protesteth, and pretendeth, too much.

Preston Estep III, Ph.D.
President and CEO
Longenity, Inc.

REFERENCES

1. Ly DH, Lockhart DJ, Lerner RA, Schultz PG. Mitotic misregulation and human aging. Science. 2000 Mar 31;287(5462):2486-92.

2. Whitney AR, Diehn M, Popper SJ, Alizadeh AA, Boldrick JC, Relman DA, Brown PO. Individuality and variation in gene expression patterns in human blood. Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1896-901. Epub 2003 Feb 10.

3. Welle S, Brooks AI, Delehanty JM, Needler N, Thornton CA. Gene expression profile of aging in human muscle. Physiol Genomics. 2003 Jul 07;14(2):149-59.

Aubrey de Grey replied as follows:

I thank Dr. Estep for his critique of my ideas and of their portrayal by Sherwin Nuland. I particularly thank him because it is so rarely that anyone with extensive knowledge of the biology of aging actually puts into words why they think my projected timescales are unrealistic (and indeed, it's the first time Estep has done so).

Firstly I must correct one statement: Estep claims that I believe that I know the cause of aging and completely understand the path to its control. That is not correct: I only claim that we know enough about the causes of aging and ways to control it that we have a 50% chance of achieving life extension escape velocity within 25 years assuming reasonable funding for the next ten years, and that having reached that point we will stay "ahead of the game" thereafter by refining those therapies faster than their incompleteness catches up with us. Again, in the second segment of his popst he discusses "full control in 20 years" -- which I do not claim we will have. He continues by losing the essence of my claims completely when he mentions the feeder cell problem: this is a problem of politics and politics alone. It has no relevance to the rate of progress in postponing mouse aging, which I claim (and have often said and written) will be the key to overturning all political objections to human rejuvenation therapies overnight.

Estep's error in his argument about entropy is to overlook the fact that cells introduced into the body in a cell therapy (of any kind) will in general have less entropy than the ones they replace did. He is quite right that they consume information while they are settling in, but thereafter they provide it. This can maintain a high degree of order indefinitely, even in the face of increasing entropy of all cells while in situ. I don't remotely deny that cell therapy is very tricky and complex -- indeed, getting the cells into the right phenotypic state before the therapy may generally be even harder than causing the right differentiation (or lack of it) in situ -- but it's not akin to building a perpetual motion machine, which is how Estep seems to characterise it. He alludes to the existence of "substantial evidence not addressed" by me and SENS, but the only references he gives are to the changes of gene expression with age, which of course occur but do not tell us anything about what can be done to reverse them.

I repeat, however, that even though this is a rather simple error (in my view) I am grateful to Estep for at least having a go at finding decisive holes in SENS. We need more of this.

Estep ends by suggesting that I am indulging in ad hominem dismissals of gerontologists who disagree with my proposals. Not so: I derive my view (that virtually no biogerontologists know enough about the state of current progress in several of the SENS areas to comment usefully on how long they will take to be completed) purely from talking to them and discovering how much they don't know. Most biogerontologists do not dispute this, which is the main reason they don't engage me in the sort of detailed, nuts-and-bolts discussion of feasibility that we need. I engage extensively in such discussion with the scientists who are actually working in these areas (sometimes even convening meetings for the purpose, documented at SENS3 and SENS4), and am constantly learning from those scientists about new difficulties and also new breakthroughs -- but those scientists are, by and large, not biogerontologists, and are working on these problems/technologies for reasons other than the postponement of aging.

In a recent Immortality Institute thread on a different - but tenuously related - topic, we can find some further interesting comments from knowledgable posters on Estep and de Grey's points. Just scroll down to read it all.

Investigating Mitochondrial DNA

Since accumulated damage to mitochondrial DNA is strongly correlated with the aging process - and possibly a cause of aging - these cellular powerhouses are a hot topic in aging research at the moment. As for all modern biology research, it is important for scientists to understand the molecular mechanisms associated with mitochondrial function and damage. Here, EurekAlert reports on the latest piece of the puzzle: "Mitochondrial DNA was discovered in the 1960s, and we still do not know much about how it is organized, packaged or inherited. What is really amazing is that we very recently discovered proteins associated with mitochondrial DNA that were thought to only have metabolic functions, and that aconitase, one of these proteins, is essential for mitochondrial DNA maintenance and inheritance."

Link: http://www.eurekalert.org/pub_releases/2005-02/uots-rau020205.php

Mitochondria - Cancer Connection

Research into both mitochondria and cancer (itself an age-related condition) is of great interest to the healthy life extension community. Here, ScienceDaily reports on a link between the two: "the excessive build-up of a simple metabolic molecule in mitochondria can trigger a sequence of events that leads to tumour growth. The discovery increases our understanding of the molecular basis of several types of cancer, which is crucial for the development of new ways to prevent, diagnose and treat the disease." Effective, targeted therapies can be produced ever more rapidly as scientists develop a greater understand of cellular processes - and their interaction - at the molecular level.

Link: http://www.sciencedaily.com/releases/2005/02/050201194815.htm

Crossing the Threshold

Alex Beam of the Boston Globe authored a rather characteristic filler piece on the Technology Review cover article profiling biogerontologist Aubrey de Grey - sniping at all sides without examining anything so prosaic as, say, the actual science involved. I am singled out as an invading crackpot at one point; I feel I've crossed a threshold of some sort. At least he bothered to e-mail me to verify my name and gender before starting in with the slander.

Still, no such thing as bad publicity. Let the know-nothings snipe and make snide remarks. If we've seen anything, it's that people open to examining the merits of healthy life extension research will hear the message loud and clear through many layers of pro-death (and other forms of) humbug.

Alternate Day Fasting Not So Great

Alternate day fasting has been suggested as a methodology of calorie restriction - but the scientific jury is still out as to whether it's any better or worse than the standard practice of simply limiting calories every day. Reuters reports that human subjects don't seem to like alternate day fasting all that much - which should be taken to be just as anecdotal as my observation that Calorie Restriction Society members seem to have few problems enjoying their diets. The lesson to take away here is that calorie restriction is proven to provide numerous health benefits and is likely to extend your healthy life span to some degree. The animal life span studies are certainly just as compelling as the human health studies performed to date.

Link: http://olympics.reuters.com/newsArticle.jhtml?type=healthNews&storyID=7500874

Examining Aging Flies

SFGate profiles the research of Pankaj Kapahi at the Buck Institute: "by feeding, poking, prodding and putting flies through a host of scientific indignities, he is searching for ways to make people live longer. ... Flies and humans share a number of metabolic processes that, when manipulated, can affect the rate of aging." On that note, it's worth mentioning that some folks are looking into starting a Methuselah Fly Prize along the same lines as the M Prize for anti-aging research in mice. Research into healthy life extension medicine - whether in flies, mice or humans - is still woefully underfunded, especially in light of what is likely to be possible with a comparatively modest level of resources.

Link: http://sfgate.com/cgi-bin/article.cgi?file=/c/a/2005/02/01/BAGL9B3FJP1.DTL&type=science

Uncovering the Mechanisms

Some recent work on cell senescence demonstrates one of my recurring points: we have reached the stage at which all new knowledge of cellular biochemistry and genetics found in the course of a single field of research has wider applications. We are seeing the ties between aging and cancer, for example, and the ways in which different conditions related to the same biochemical processes.

Earlier studies have demonstrated that as cells reach senescence, an alteration in chromatic structure called senescence-associated heterochromatin foci (SAHF) silences the genes that trigger the cells growth. This discovery reveals the process of SAHF formation. SAHF are domains of tightly packed chromatin that repress activity of the genes that normally trigger cell proliferation. The Fox researchers have identified at least three proteins in the cell that contribute to the formation of SAHF. These proteins are called ASF1a, HIRA, and promyelocytic leukemia (PML). Scientists have known for a while that PML suppresses the formation of this type of leukemia, but do not know why.

This research suggests the possibility that PML arises because the PML protein is not able to do its job in forming SAHF. If this is true, this study might help in the design of therapeutic drugs to treat cancer patients and even lessen some aspects of aging. Additional study in this field will define the molecular details by which HIRA, PML, and ASF1 and formation of SAHF may also be a factor in other human cancers.

The incidental benefits of fields like stem cell research and modern cancer research - focusing as they do on cellular biochemistry - are large. This new knowledge will serve as a basis for the targeted healthy life extension research of the future.

Obesity And Type 2 Diabetes

(From Boston.com). The link between obesity and age-related (type 2) diabetes has long been known: "The researchers, from Joslin Diabetes Center in Boston, discovered a genetic 'master switch' in the liver that is turned on when people become obese. ... this switch produces low-level inflammation, which disrupts the body's ability to process insulin, causing type 2 diabetes." As usual, understanding allows potential therapies to be explored quite rapidly. "Reasoning that aspirin-like drugs are used to quell inflammation, they successfully used the drugs, called salicylates, to eliminate the symptoms of type 2 diabetes in mice. Human tests are already underway in Boston, though no results have been published." The best therapy is, of course, a lifestyle that avoids obesity in the first place.

Link: http://www.boston.com/news/globe/health_science/articles/2005/01/31/researchers_find_diabetes_trigger_possible_fix?pg=full

Do All Bacteria Age?

Nature reports on an elegant photographic experiment that has detected the signs of aging (or senescence) in certain bacteria, once thought to be immortal. "E. coli divides down the middle, giving each daughter cell one newly regenerated tip. But the cell's other tip is passed down from its mother, or grandmother, or some older ancestor. The bacteria inheriting the older end reproduced 1% more slowly than their counterparts with each cell division ... Discovering how to monitor bacterial lifespan may help us understand the genes that control human ageing, which are implicated in everything from weakened immunity to sagging skin."

Link: http://www.nature.com/news/2005/050131/full/050131-6.html

More On Stem Cell Work From Randall Parker

Randall Parker makes some helpful observations on scientific progress towards controlling stem cells:

I think it is inevitable that methods will be found to dedifferentiate (i.e. make less specialized or less committed to a single purpose) both adult stem cell types and fully specialized cell types (e.g. liver cells or skin fibroblast cells) to turn these cells back into less differentiated stem cells and even all the way back into embryonic stem cells. So for the production of motor neurons we will not always be limited to starting with embryonic stem cells to pass them through that 2 week window in early embryonic development during which embryonic stem cells can be converted into motor neurons. In fact, compounds that cause cellular dedifferentiation have already been found. I expect many more techniques for dediffentiating cells will be found.

Think of cells as enormously complex state machines. Currently it is much easier (though not easy in an absolute sense) to coax cells to switch from the embryonic state into other states. The reason for this is pretty obvious: Cells in the embryonic state must be capable of transitioning through a series of steps into all the other states (e.g. to the state that heart muscle cells are in or the state that liver cells are in or the state that insulin-secreting Pancreatic Isles of Langerham cells are in) because embryos develop to produce cells in all those states. They must have that capacity or else a full organism couldn't develop starting from an embryo. However, just because there are some cell state transitions that do not happen under normal conditions of development that doesn't mean that those transitions can't be made to happen with the right (and waiting to be discovered) sequences of hormones, growth factors, gene therapies, and other stimuli.

Just because some day we will have methods to turn non-embryonic cell types into all other cell types that does not mean that avoidance of the use of hESCs in developing therapies has no future cost in terms of the health of some fraction of the human population. There is a very real possibility that hESCs can be developed for some therapeutic uses faster than other cell types can be developed for all uses. My guess is that at least for some purposes hESCs will be ready to provide treatments faster than adult stem cell types can be coaxed to do the same. We will see more research results such as this paper offering the possibilty of a cell therapy treatment for which the development of alternative non-hESC based cell therapy treatments are a more distant prospect.

I view research into stem cell based regenerative medicine as a real boon - in addition to all the obvious end goals, it is forcing scientists to uncover, understand and eventually manipulate the fundamental workings of our cells. Much like cancer research and AIDS research required the development of new basic science that has proven its worth across the board, stem cell research is spurring development of a scientific groundwork for the advanced medicine of decades to come.