The Youth Pill

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;http://www.longevitymeme.org/articles/viewarticle.cfm?article_id=12 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;http://ibgwww.colorado.edu/tj-lab/frame_people1.html linkurl:reported;http://www.ncbi.nlm.nih.gov/pubmed/8608934 that a gene mutation in nematodes could more than double their life spans. Five years later, linkurl:Cynthia Kenyon;http://kenyonlab.ucsf.edu/html/ck_biosketch.html at the University of California, San Francisco, linkurl:nailed a similar worm "gerontogene";http://www.ncbi.nlm.nih.gov/pubmed/8247153 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,;http://www.siumed.edu/medicine/geriatricslab/ 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;http://www.ncbi.nlm.nih.gov/pubmed/8900272 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;http://www.ncbi.nlm.nih.gov/pubmed/19587680 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__,;http://www.amazon.com/Youth-Pill-Scientists-Anti-Aging-Revolution/dp/1591843340 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;http://www.the-scientist.com/article/display/23191/ 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, linkurl:www.davidstipp.com.;http://davidstipp.com/
**__Related stories:__***linkurl:Shock and Age;http://www.the-scientist.com/article/display/57461/
[June 2010]*linkurl:The Longevity Dividend;http://www.the-scientist.com/article/display/23191/
[March 2006]*linkurl:The Age of Senescence;http://www.the-scientist.com/article/display/23041/
[February 2006]

The Youth Pill

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