The Pursuit of Longevity

Long-lived worms tantalize researchers with the promise of extended life. In the meantime, though, they suggest cures for chronic diseases of old age.

DAVID EWING DUNCAN

In the University of California at San Francisco�s new, silver-skinned lab complex at Mission Bay, Cynthia Kenyon, Ph.D., shows me a video that she frequently parades in front of investors, journalists, and PBS audiences: millimeter-long worms bioengineered to live more than twice as long as usual. In 1993, Dr. Kenyon, a molecular geneticist at UCSF, made global headlines when her lab discovered that the suppression of a single gene, DAF-2, could extend a nematode�s life span. A key component in the genetic pathway that regulates endocrine signaling and resistance to oxidative stress (that is to say, the damage done when cells use oxygen in metabolism) the natural silencing of DAF-2 triggers a kind of slowing down in worm larvae during times of extreme environmental pressure (for instance, a lack of food), allowing the larvae to survive. When Dr. Kenyon suppressed DAF-2 in adult worms, they lived 45 days instead of the usual 18 days—and they remained vigorous and healthy until close to the end.

Dr. Kenyon�s finding shocked biologists, who had long assumed that something as complex as aging couldn�t be affected by a single gene, even in nematodes. Hundreds, possibly thousands, of human genes are known to contribute to aging, influencing everything from baldness to dementia. Yet I see the evidence on Dr. Kenyon�s video monitor: a normal, 3-day-old worm in the prime of life, a Caenorhabditis elegans (whose simple genetics and cell structure make it a favorite of geneticists) is wriggling in a broth of nutritious bacteria. At 13 days, the worm is sluggish, its head barely stirring as death approaches. The next images are of a mutant worm, with the knocked-down DAF-2 gene, which at 25 days is still squirming away.

“This video says more than 20 Nature articles [can say],” says Dr. Kenyon, a thin, youthful 49 year old. What she tells me next is harder to accept: her mutant worms and other recent breakthroughs in antiaging, might hold the key to extending life in far more complex organisms—even in humans. “Worms are worms, and humans are humans,” she says, “but I see no reason yet why this shouldn�t work in people.”

Once a moribund field out on the fringe, antiaging science has witnessed an impressive list of discoveries since Dr. Kenyon�s DAF-2 research appeared in Nature a decade ago.¹ The most enthusiastic researchers contend that the days of normal aging in humans may be numbered. Most interesting, they argue that people will not age like Tiresias—that is, by enduring a wizened old age. They believe that the manipulation of genes like DAF-2 and other age-retarding remedies will extend youth in humans, as it has for worms, flies, and mice.

1  Kenyon, C. et al. (1993) A C. elegans mutant that lives twice as long as wild type. Nature 366:461�4.