The Youth Pill

A new book explores the science behind the quest to extend healthy life span

By David Stipp | June 25, 2010

No scientific advances inspire more media hype than ones in gerontology, the study of aging. Even the crustiest editors have been known to turn giddy when new light is shed on the topic and take to blowing raspberries at the Reaper with headlines suggesting immortality elixirs are just around the corner.
Biologists aren't so easily wowed, though, and before the mid-1990s they generally saw gerontology as a dismal bog where once-promising peers sank out of sight, or worse, re-emerged clutching beakers of snake oil. Compelling logic underlay the dismissiveness: Natural selection has sculpted our genes to care about getting to the next generation, not about keeping our bodies youthful for a long time. Thus, soon after we reach reproductive age, our genes' preservative influence fades, and escalating random damage sets in. Studying the details of this inexorable, chaotic decay seemed a waste of time to most life scientists. And attempting to block or slow it seemed utterly quixotic. In 1957, evolutionary biologist George Williams linkurl:encapsulated the conventional wisdom; by equating the anti-aging quest to the hunt for perpetual motion. Then in 1988 a miracle happened -- the University of Colorado's linkurl:Thomas Johnson; linkurl:reported; that a gene mutation in nematodes could more than double their life spans. Five years later, linkurl:Cynthia Kenyon; at the University of California, San Francisco, linkurl:nailed a similar worm "gerontogene"; dubbed __daf-2__. These flabbergasting discoveries revealed that not everything about aging is intractable chaos -- worms, at least, apparently possessed gene-encoded modules poised to oppose the ravages of advancing age when activated by a single mutation. Optimists soon speculated that similar modules exist in mammals. But for several years after the discovery of worm gerontogenes, it wasn't at all clear that mammals possess such modules. After all, __daf-2__ and related genes were known to work by activating a semblance of the "dauer phase," a kind of suspended animation that enables nematode larvae to ride out food shortages, and there's a lack of evidence that we warm-blooded types similarly turn into living mummies when the larder is bare. But then two remarkably persistent scientists settled the burning issue -- and solved a murine murder mystery in the process. One was linkurl:Andrzej Bartke,; an endocrine researcher at Southern Illinois University in Carbondale who'd long nurtured the world's only colony of Ames dwarfs -- mice whose growth is stunted by a mutation in the __prop-1__ gene, which curtails the production of growth hormone. The dwarfs were widely regarded as delicate, short-lived runts. But Bartke disagreed. He'd watched giant transgenic mice, which over-express growth hormone, undergo what seemed accelerated aging, and so had guessed that his dwarfs' hormone deficiency might actually boost their longevity. Proving his hunch wasn't easy. Mammalian life span studies are the grueling marathons of life science. Conducting one with normal mice typically takes two to three years; Bartke knew that proving his dwarfs' age slowly could easily take more than four. That represents perhaps 15 percent of a researcher's entire career. And history has repeatedly shown that the length of such experiments increases the risk that diseases or stresses will crop up that shorten the rodents' lives and ruin everything. Still, in 1993 Bartke and two postdocs pitted 34 Ames dwarfs against 28 of their normal siblings in a slow race to the death. A little over three years later, linkurl:their data showed; that the dwarfs were living 50 percent longer than the controls. But while preparing to report the discovery, Bartke learned that researchers at The Jackson Laboratory in Maine had earlier found that Snell dwarfs -- mutant mice nearly identical to Ames dwarfs -- were short-lived. Fearing his lab's contrary finding would be dismissed as a fluke, he phoned Kevin Flurkey, the Maine lab's dwarf mouse keeper, to compare notes. It turned out that despite the earlier findings, Flurkey had a hunch about the dwarfs' longevity and had more recently launched a new life span study on them. After 18 months, his data had indicated the females were strikingly long-lived, but the males were dying very young. Then one day Flurkey had witnessed one of his male "caretaker" mice -- normal mice caged with the easily-chilled dwarfs so they can snuggle up and keep warm -- apparently trying to throttle a dwarf. Suddenly it clicked: He'd always caged his dwarfs with same-sex caretakers, and male mice have been known to kill pups sired by other males. Further, adult dwarf mice resemble pups. No wonder his Snells had generally seemed short-lived -- lots of them were being murdered in the night by mice three times their size. Not long before Bartke phoned, he'd realized what was happening and placed his surviving Snell males with female caretakers, where they'd lived happily ever after -- or at least a lot longer than the controls. Bartke and Flurkey wound up extending the gerontogene revolution to mammals, and now more than a half dozen gene mutations are known to boost mouse longevity. While it's not known whether human gerontogenes exist, the mouse discoveries argue that an ancient, evolutionarily conserved anti-aging module is likely embedded in our genomes that could dramatically extend our healthy life spans if cleverly tweaked with drugs. Last year another landmark mouse study linkurl:gave an exciting hint; that the module is coming into view: Researchers showed for the first time that a drug could convincingly extend life span in mammals. Called rapamycin, the drug inhibits __mTOR__, a gene found in all mammals, suggesting that it may be a key part of an anti-aging module that can be readily manipulated. linkurl:__The Youth Pill: Scientists at the brink of an anti-aging revolution__,; by David Stipp, Penguin Books, London, 2010. 320 pp. ISBN: 978-1-617-23000-4. $26.95. David Stipp is a freelance science writer, formerly with the __Wall Street Journal__ and __Fortune__, who has extensively covered gerontology since the late 1990s. One of the key inspirations for his new book on the topic was a linkurl:2006 article; in __The Scientist__ calling for pursuit of the "longevity dividend" promised by anti-aging research. He recently launched a blog on aging science at his website,;
**__Related stories:__***linkurl:Shock and Age;
[June 2010]*linkurl:The Longevity Dividend;
[March 2006]*linkurl:The Age of Senescence;
[February 2006]


Avatar of: Vinod Nikhra

Vinod Nikhra

Posts: 48

June 25, 2010

Ageing is an enigma. We find people ageing; we ourselves age and grow older. The phenomenon of ageing is universal in the kingdom of living. With time, all living beings age. Yet, we do not understand it. We do not know, why do we age or what makes us age and grow old, finally losing vitality of life? \n\nThere have been immense developments in scientific research, which includes medical science as well. There has evolved a whole novel understanding of the biology of ageing. A vast body of knowledge can explain the changes that take place with ageing at molecular and cellular level. At the same time, the progress in health care and technology makes it possible to slow ageing. There are possibilities of being able to reverse the ageing process. \nThe hopes apart, any sort of life extension may be complicated with undesirable outcomes. The readers may find interesting to go thr' a chapter, "DARKER-SIDE OF LIFE EXTENSION: \nThe Tithonus Option, Etc." from my book, "Ageing slowly, Living longer". I am reproducing the same here.\nCHAPTER TWELVE\nDARKER-SIDE OF LIFE EXTENSION:\nThe Tithonus Option, Etc.\nTHE FEARS ASSOCIATED\nWITH EXTENDED LIFE\nFuture technology appears to offer us\nvisions that rival the dreams of myth and\nlegend. As per the Clarke's Law: ?any\nsufficiently advanced technology is\nindistinguishable from magic.? One of these\ndreams is that of extended life. It appears\nthat with the advancements in medical\nscience, genetics, biotechnology, coupled\nwith those in nano-science, a true extension\nof human lifespan will come in the near\nfuture. However, it may come at a price.\nThe Tithonus Option:\nThere is a fear that the anti-ageing\ntechnology may present us with the\nextended lifespan but limited improvement\nin quality of life. The nightmare, that we will\nlive longer, but in bad health and mental\ndeterioration, has been called Tithonus\noption - immortal life with sub-functional\nbrain or eternal dementia.\nThe Story of Tithonus: Tithonus was a\nmortal, who fell in love with Eos, the\ngoddess of the dawn in Greek\nmythology. The goddess, Eos, knowing that the mortal,\nTithonus was destined to age and die,\nbegged Zeus, the supreme god of ancient\nGreek mythology and counterpart of Roman\ngod Jupiter, to grant her lover an immortal\nlife. Zeus, the jealous god, granted the wish\nbut not the eternal youth. Tithonus aged,\nbecoming increasingly debilitated and\ndemented, eventually driving Eos to\ndistraction. In despair, she turned Tithonus\ninto a grasshopper. In Greek mythology,\nthe grasshopper is immortal.\nThere are several foreseeable outcomes\nfrom the anti-ageing technology. Today, the\nmajority of people living in the developed\ncountries can expect to live well into their\nseventies. Even so, the final years are\nusually marked by impaired health and\noften senile dementia. Here, three possible\nfuturistic outcomes may seem probable:\nThe first, we will live and die as we do\ntoday. There may accrue no benefit of\nageing research. The second possibility,\ncalled the Tithonus option, is that the\ntechnology will give extended lifespan but\nwill not be able to reduce prevalence of\ndementia and debility. The third possibility\nis that technology will be able to repair the\ndamage done with age to our\ntissues, including neurons, thus granting us\nlongevity with good quality of life.\nLife on Support Systems:\nIn the intensive care units, it is\ncommonly seen that for the critically ill\npatients, more and more invasive procedures\nare performed to save the life and more and\nmore of vital functions are taken over by biomachines.\nThe ventilator drives the\nrespiration, bolus and continuous infusion of\nintravenous fluids and drugs provide the\nnutrition and support the vital functions.\nSometimes, the heart and lung machine\ntakes over. The person is considered living till\nthe brain functions. It is an artificially\nprolonged life on support systems, amounting\nto a nightmare of proportion of the Tithonus\noption: a long life, with zero quality of life.\nSuperficially, this may seem a possibility.\nWhile genetic engineering and nanotechnology\nmay help in extending the life\nsignificantly, it does not follow that future\ntechnology will be able to repair all wear-andtear\non the brain and body organs. If the\nfuture technology can not repair all\nmicroscopic injuries, the Tithonus option will\nresult. Just consider the renal disease\npatients in whom the kidneys have totally\nfailed, they are maintained on dialysis since\neven a poor-quality-of-life is better than no\nlife. Will we not fall in the same trap, finally\nconciling ourselves to Tithonus option? People\nmay regard it better than cryopresevation in\nhope of a novel treatment in the remote\nfuture. Thus, the Tithonus option is feared.\nThe optimistic scientists, though, think that\nthe Tithonus Option is not a likely outcome\nfor various reasons.\nTHE FUTURE VISIONS\nAND THE GURSKY OPTION\nCurrent patterns of death: The\ndeath rate increases exponentially because\nour bodies accumulate damage. The\naccumulated mutational load over time leads\nto errors in DNA leading to cancer. It takes\nyears of accumulated mutations for cells to\nbecome cancerous.\nThe vascular disease is the result of\nnarrowing and plaque deposition in arteries\nbecause of the atherosclerosis process. The\nheart attack occurs when blood supply is\ninterrupted to a part of heart. The stroke\noccurs when a clot breaks off from an arterial\nplaque and lodges in an artery supplying a\npart of brain. A stroke can also occur when\nan artery bursts in the brain, pouring out\nblood under pressure. The resulting blood clot\ndamages brain tissue by a direct pressure\neffect. As such, the vascular disease\nrepresents an example of accumulated\nerrors.\nThe accidental deaths follow a complex\ncurve. Young people are more likely to die of\naccidents than those older. This is due to the\nhigher prevalence of risk-taking behaviours.\nAs the age increases, there comes awareness\nfor safety. The elderly, too, are more likely to\ndie because of accidents. Reduced balance\nand co-ordination, delayed response,\nmuscular weakness and osteoporosis put the\nelderly at greater risk of having an accident.\nBut, here, the accidental deaths show an\nexponential curve because, they are the\nresult of accumulated damage.\nThe Gursky option: The diseases of\naccumulated damage are destined to be the\nprimary causes of death in developed\ncountries. Also, with development, other\ncountries will reduce the rate of infections,\nfalling for the death patterns like in\ndeveloped countries.\nThe only possible escape from the\ndiseases of accumulated damage, is\ndeveloping advanced medical technologies\ncapable of repairing the bodily errors. This\nis called the Gursky option. So named after\nIan McDonald's novel, The Days of Solomon\nGursky, where the life of a nanotech\ndesigner?s inventions allow humans to stave\noff disease and improve their bodies.\nThe exponential death rates and\nincreasing debility go hand in hand. By\nsolving one, the other shows a favorable\ntrend. By decreasing cancer and accident\ndeaths, we can look forward to reduce\ndebility. Therefore, developing the antiageing\ntechnology will not lead to the\nTithonus option but rather the Gursky\nsolution.\nEFFECTS OF EXTENDED\nLIFESPANS ON THE SOCIETY\nTHE VISION OF LIFE EXTENSION\nTo stay alive is a basic human drive. It is\na precondition for all other activities. Lifeextension\nis the natural progression of curing\ndiseases by treatment and preventing the\neffects of ageing altogether. The human life is\nsacred and should be cherished and\npreserved.\nTHE FEARS OF SOCIAL BURDEN\nThe extended life spans will definitely\naffect human society. It will bring positive\neffects on society of a host of people with the\nwisdom of 150 years of life and the youthful\nvitality.\nThe issue of overpopulation should not\nbe feared. In technologically advanced\nsocieties, couples tend to have fewer\nchildren, often below the replacement rate.\nBy spread of benefits of technology,\neducation, and women?s rights, fertility rates\nwill decline. As the UN population studies\npredict, over-population is an unlikely\nproblem.\nLife extension will not place a burden on\nhealth care, as feared. The life extension,\nitself, is likely to be associated with good\nhealth and disability limitation. The older\nadults with extended life will be economically\nproductive members of society.\nBORING LONG LIFE? NOPE.\nPeople on learning life extension\nprojects, or sometimes, even scientists, air\nthe fear that living very long may be boring.\nBut, feeling bored is a state of mind. The\nstate is never permanent, it is a transient\nphase influenced by immediate situations. We\ndiscover new things, find something hidden in\nthe things known for long and feeling of\nboredom passes away, replaced by the joy of\nexcitement.\nTHE NON-AGEING WORLD\nBy eliminating a majority of age-related\ndiseases and maintaining the vitality of the\nbody for a very long time, we can look\nforward to achieve a significantly long life\nspan of more than 1,000 years.\nThis estimation of future average life\nspan of 1,000 years has been reached by\nconsidering the removal of age-related\nmortality from current statistics. Accidents\nand other such causes of death will still\nremain.\nThe anticipated problem of overpopulation\napart, there will be the danger\nthat people considered threats, someone like\nHitler and Stalin will remain in power much\nlonger than they would if they faded away or\ndied because of ageing. Criminals, too, would\nlive longer like characters in cartoon films,\ncontinuing to pose a threat.\nThe delayed ageing will lead to various\nsocial changes. The age stratification in the\nsociety will disappear, and along with it,\nmany of our current social mores. The new\nideas and new possibilities will evolve.\n\nVinod Nikhra, M.D.\\\n\n
Avatar of: anonymous poster

anonymous poster

Posts: 4

June 25, 2010

"The vital component of Darwin?s contribution was that evolution occurred by natural selection. This process he defined as favouring the survival of those organisms that leave the most progeny who will themselves successfully reproduce. The latter half of the sentence is important because it means that selective advantage will continue to act for many years after breeding. There is a clear advantage for humans in living long enough to bring up their children to sexual and economic maturity, which can take between a quarter and a third of the normal life span. The naive idea that natural selection ceases to act after active reproductive life is therefore certainly incorrect." (From Lachmann P (2010)"Genetic and Cultural Evolution: from fossils to proteins; and from behaviour to ethics" European Review 18:297-309
Avatar of: Steven Brenner

Steven Brenner

Posts: 14

June 26, 2010

Probably rather than prolonging aging, the only solution to longevity will be to extend youth. \nMost of the diseases of aging are not seen in youth, thus to avoid the ravages of aging, it will be necessary to maintain youth. \nThe prime diseases of aging, Alzheimer, Parkinson's in the brain, atherosclerosis in the vascular system, osteoarthritis in the skeletal system, cataracts in the eyes as well as macular degeneration in the retina are all related to aging. \n Finding the key for maintenance of youth will probably be necessary to avoid the ravages of aging. \n Does this mean extending puberty or that state prior to reproduction for true longevity to occur, or to extend childhood? Possibly. \n With the current state of modern technology, I think most likely a continued and extended state of symbiosis between man and machine, with pacemakers, defibrillators, even artificial hearts, kidneys and lungs being developed for implantation. We are seeing the dawn of such an age. Is it an age people will choose to live?\nCertainly now people are choosing to live in symbiosis with machines, and are becoming in closer relationships with them. \n It will require continued research and development, which is enormously expensive. \n Will only those of great wealth be the beneficiaries, possibly so. Currently those with wealth are more likely to live longer than those in poverty, and such a trend can be expected to continue. \n I think possibly the ancient stories of longevity such as Methuselah in the Bible who lived nearly a thousand years may have some basis in fact, perhaps persons who lived for extended periods of time in a more pristine environment. \n Does that mean something has been lost, perhaps a genetic heritage which might be regained or rediscovered? Possibly so. \n I think it is worth a look, although it would require time, effort and commitment, all things in short supply in modern times. \n There is more commitment to destruction, war, domination and the search for wealth rather than for those things leading to truth and beauty. \n First the priorities must be set, then the quest can begin, however the destination may not be that which is expected or even hoped for. \n Thanks\n
Avatar of: Sean McHugh

Sean McHugh

Posts: 2

June 26, 2010

Most living things are immortal - the vast majority, in fact. This does not mean they cannot be killed. They are single cells and viruses. Viruses alone kill half the planet's bacteria every day. Even so, it is statistically likely that somewhere one of the original bacteria of billion years ago, is placidly living on somewhere.\n\nAs to why larger animals age and die - I suggest it is an anti-cancer trick of evolution.
Avatar of: Anthony Gelbert

Anthony Gelbert

Posts: 50

June 27, 2010

Now we know why Warren Buffett and Bill Gates are funding so much research in "vaccines" (right- uh huh). And why does so much of this "work" go on in Africa? Do you know why the USA became the leader in medical advances beginning around 1890 (yes, EIGHTEEN ninety)? It was because of our experimentation with humans who had no public voice and were mostly unaware of their use as lab rats. Do you know why the african american community disdained the H1N1 vaccines? They, with good reason, do not trust our lilly white medical community. I would not put it past our rich elite to privately fund medical longevity research on human subjects in african countries for the despicable purpose of extending life for a select few. Perhaps Dr. Bartke can tell us if he has been approached.

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