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Kenyon's Ageless Quest

A San Francisco scientist's genetic research renews the ancient hope for a way to slow aging

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The poster taped to the door of Cynthia Kenyon’s office at the University of California at San Francisco seems so ordinary that you would hardly suspect it advertises a revolution in human affairs. It announces a talk she was about to give on genes that influence the life span of a type of nematode, a tiny worm that lives in soil. The poster shows a cartoonish illustration of a wizened little worm hobbling along with the help of a cane, while half a dozen human infants, in diapers, splash in the spray of a fountain. Despite the whimsical drawing and the mischievous title of Kenyon’s lecture, “Genes from the Fountain of Youth,” she’s not kidding. Since the early 1990s, Kenyon, a molecular biologist, has produced a body of research about this simple organism that has broad implications. She and her collaborators have doubled, quadrupled, and in some instances sextupled the worm’s life span by manipulating several of its genes. And others have found that the same metabolic pathway, controlled by genes, appears to function in other organisms, including yeast, fruit flies and mice. The question is whether it also functions in people—and might be manipulated to extend human life.

Many scientists say no, but Kenyon is betting on yes. Four years ago, she co-founded a biotechnology company, Elixir Pharmaceuticals, in Cambridge, Massachusetts, to develop drugs and other products to treat age-related diseases and slow down the process of aging. Another company cofounder, Leonard Guarente, an MIT biologist and an old friend of Kenyon’s, has suggested that the company might, within a decade, develop a pill that could add 10 to 30 years to a person’s life. “We may not have a perfect drug in 10 years, but we’ll have something to build on,” says Kenyon, 50. “Potentially, we could have it sooner.”

Elixir is one of about a dozen small biotechnology companies jumping into the fountain-of-youth business. Only a decade or so ago, the pool was pretty empty, unless you counted the pseudoscientists and snake-oil salesmen who have historically hawked anti-aging nostrums. But genuine advances in genetics and the study of stem cells, unspecialized cells that can be coaxed to develop particular functions and thus might replace damaged tissues, have engendered new ways of thinking. “The thing about aging,” Kenyon says, “was that everybody thought, ‘Well, you know, the animal just breaks down, and what’s to study, really? It’s not going to be very interesting.’ But when I looked at it, I could see that different animals have different life spans.” Consider a mouse, a canary and a bat. “The mouse lives two years and the bat can live 50 years and the canary lives about 15 or so years. They’re all small animals. They’re warmblooded. And they’re not that different, really, in such a fundamental way from each other.”Afairly small number of genes, she argues, may control the creatures’ differing life spans.

To a lot of biologists, aging research has not always been a respectable calling. When Kenyon’s lab first began to work in the field, she insisted that her co-workers avoid even using the “a-word” in research reports and grant applications. “It was embarrassing to say we were working on aging,” she says. “The field had a reputation for going nowhere.” To be sure, life extension is still subject to wild exaggeration and implausible predictions, but the field has progressed tremendously, and Kenyon’s research has had a lot to do with that. “The field needed an injection of fantastic talent, people like Kenyon and Guarente,” says Gordon Lithgow, a molecular biologist at the Buck Institute for age research in Novato, California. “They’re great communicators, but they’re also just the tip of the iceberg. There’s some great science coming out of this area.”

The marriage of molecular genetics, our most precise and vaunted life science, with perhaps the oldest and most alluring human fantasy—eternal youth—is one of the most intriguing aspects of recent gerontological research. Given the moral embedded in the misfortune of Tithonus—the sad sack of Greek mythology whose wife mistakenly asked the gods for eternal life for him instead of eternal youth, causing him to wind up in an endless purgatory of decrepitude—the myth of a fountain of youth has been part of the record of human longing for at least two millennia.

If Tithonus gave that longing a cautionary quality, ancient cultures, notably the Egyptians and Chinese, gave it an aura of quackery, at least to modern eyes. More than 2,000 years ago, Chinese alchemists known as “thaumaturgists” devoted considerable energy to creating “drinkable gold” as a means of prolonging life. “The king of the state of Chu was presented with an ‘elixir of deathlessness’ by thaumaturgical technicians,” notes a Chinese text of around 400 b.c. (which did not, however, reveal if the potion worked). Gerald J. Gruman, a historian who has surveyed life extension, writes that “interest in the fountain of youth had reached an apex in the fourteenth and fifteenth centuries, and the discovery of America gave a new impetus to the tradition in the early years of the sixteenth century.”

It was Juan Ponce de León, of course, who put a more modern face on the myth and gave it an enduring ethos of futility. Legend has it that, around 1509, while serving as governor of what is now Puerto Rico, he first heard tales about a fountain or spring on Bimini, an island to the northwest, that rejuvenated anyone who drank from it. Intrigued perhaps more by reports of gold than rejuvenating waters, Ponce de León mounted an expedition in March 1513. He failed to find either Bimini or the “Fountain of Youth,” but within a month or so did discover Florida.

The search for youthful immortality took a notably pseudoscientific turn in 1889, when the respected French scientist Charles-Edouard Brown-Sequard claimed he could rejuvenate old men with an injection containing crushed dog testicles. Though the claim was mistaken, it incited scientific races in the early 20th century to isolate the male hormone testosterone and the female hormone estrogen, which have long been promoted by physicians and charlatans alike as anti-aging tonics.

On Kenyon’s office bookshelf, Lewis Carroll’s Alice’s Adventures in Wonderland and Edgar Allan Poe’s Tales of Mystery and Imagination sit alongside James D. Watson’s The Molecular Biology of the Gene, a combination that hints not only at the breadth of Kenyon’s interests but the way they straddle popular culture and hard-core science. Even her scientific papers are accessible. “The process of aging influences our poetry, our art, our lifestyle, and our happiness, yet we know surprisingly little about it,” she writes in the data-thick, jargon- strewn journal Cell.

Born in Chicago and raised in Georgia, New York, New Jersey and Connecticut, Kenyon attended the University of Georgia, where her father was a member of the geography faculty and her mother worked as an administrator in the physics department. Cynthia Kenyon traces her passion for genetics to the day her mother brought home Watson’s The Molecular Biology of the Gene, which taught her, she recalls, “about switching on and off genes in bacteria. I just thought it was fabulous.” After graduating as class valedictorian in 1976 with a degree in biochemistry, Kenyon moved on to MIT, where she got her PhD. She then spent five years at CambridgeUniversity in England, where she was tutored in the ways of one of the lowliest and yet most astonishingly instructive creatures to crawl out of the ground: the nematode.

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