Monday, April 3, 2006

The Fountain of Health -- Part 1

Antiaging research could provide a powerful approach to treating the many diseases of old age.

By David Rotman

This article -- a feature story in Technology Review's March/April 2006 print issue -- has been divided into two parts for presentation online. This is part 1; part 2 will appear on Tuesday, April 4.

For the better part of two decades, Richard Weindruch, a professor of medicine at the University of Wisconsin-Madison, has fed half of a colony of 78 rhesus monkeys a diet adequate in nutrition but severely limited in calories -- 30 percent fewer calories than are fed to the control group. Scientists have known for nearly 70 years that such calorie restriction extends the life span of rodents, and Weindruch is determined to find out whether it can extend the life span of one of man's closest relatives, too.

It's too early to know the answer for certain. The monkeys in Weindruch's lab are only now growing elderly. And with 80 percent of them still alive, "there are too few deaths" to indicate whether the animals on the restricted diet will live longer, says Weindruch. But one thing is already clear: the monkeys on the restricted diet are healthier. Roughly twice as many of the monkeys in the control group have died from age-related diseases, and perhaps most dramatically, none of the animals on the restricted diet have developed diabetes, a leading cause of death in rhesus monkeys.

These encouraging, albeit preliminary, results are sure to cheer those few who have adopted severe calorie-restricted diets in hopes of living longer. But their real significance is the further evidence they provide that calorie restriction affects the molecular and genetic events that govern aging and the diseases of aging. Indeed, while calorie restriction remains impractical for all but the most determined dieters, it is providing an invaluable window on the molecular and cellular biology of disease resistance and the aging process.

Up until a decade or so ago, most biologists believed that the aging process was not only immensely complex but also inevitable. People aged, they assumed, much the way an old car does: eventually, everything just falls apart. Then in the early 1990s, Cynthia Kenyon, a young molecular biologist at the University of California, San Francisco, found that mutating a single gene, called daf-2, in worms doubled their life spans. Before the discovery, says Kenyon, "everyone thought aging just happened. To control aging, you had to fix everything, so it was impossible." Kenyon's research suggested a compelling alternative: that a relatively simple genetic network controlled the rate of aging.

The race to find the genetic fountain of youth was on. Within a few years, Leonard Guarente, a biologist at MIT, found that in yeast, another gene produced a similar dramatic increase in life span. Soon after, Guarente and his MIT coworkers made another startling discovery: the yeast antiaging gene, called sir2, required for its activity a common molecule that is involved in numerous metabolic reactions. Guarente, it seemed, had found a possible connection between an antiaging gene and diet. The gene, Guarente thought, might be responsible for the health benefits of calorie restriction; and indeed, the lab soon confirmed that calorie restriction in yeast had life-extending effects only when sir2 was present.