March 2006

The Fountain of Health

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Since the discovery of these and other antiaging genes in lower organisms, the scientific search for live-longer genes in people has, not surprisingly, garnered much publicity. Often lost in the excitement about the prospect of triple-digit birthdays, however, is a far more realistic and immediate implication of the research. While learning how to extend the life span of humans could take many decades, if it's even possible, researchers are already using insights gained from studies of aging and the effects of calorie restriction to search for new drugs to treat the numerous diseases tied to getting old.

The incidences of many illnesses, including cardiovascular disease, Alzheimer's, and cancer, rise nearly exponentially with age. And while we still don't know exactly why, we do know that calorie restriction -- at least in test animals -- delays the onset of a broad swath of these age-related diseases. "It's something people are surprised to hear, because it really begs the question, how is that possible? There must be some common metabolic component. But no one really knows how all those diseases can be tied together," says Guarente. Nevertheless, some biologists hope that a drug that mimics the molecular effects of calorie restriction might also delay the onset of some or all of these diseases.

At least one company, Sirtris, a small but heavily funded startup in Cambridge, MA, believes it is close to finding such drugs. The company, which boasts an impressive group of prominent molecular biologists and geneticists on its scientific board, was cofounded by David Sinclair, a former postdoctoral researcher in Guarente's lab and now an associate professor at Harvard Medical School. Sirtris has come up with hundreds of molecules that activate the SIRT1 enzyme, which is produced by the mammalian homologue of sir2. (Seven different SIRT genes have been found in humans; these and their homologues in other species are collectively known as sirtuins.) If the company is on the right track -- and Sirtris says potential drug candidates for treating diabetes and neurodegenerative diseases are expected to begin preliminary human tests over the next several years -- the molecules could mimic the genetic effects of calorie restriction, offering its apparent health benefits without its drawbacks.

"It's known that calorie restriction greatly enhances the body's natural ability to fight diseases," says Sinclair. The vital questions, he says, are what controls that process and whether we can develop drugs to target it. "We don't assume we know everything about it, but we do strongly believe that sirtuins are a major component in what could be a master regulatory system for human health."

The Fountain of Health

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