March 2006

The Fountain of Health

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Risk Factor
At Elixir and Sirtris, there is little talk about slowing down the aging process. Rather, both companies are intensely focused on the discovery and development of drugs for various age-related diseases, such as type 2 diabetes. Sirtris's Westphal puts it bluntly: "I was never interested in a company that would try to prolong life. I was interested in a company that was going to use genes involved in diseases of aging and in finding an FDA-approved path to get those drugs approved for important disorders like diabetes and neurological disorders."

Nevertheless, antiaging research and drug discovery efforts like Sirtris's and Elixir's are closely linked and share a common premise; a few master genes are thought to regulate both the body's ability to fight off diseases associated with aging and the extension of life span. Though it is still a controversial hypothesis, Sinclair and Guarente believe that in times of adversity or stress -- when food is scarce, for instance -- sirtuins somehow marshal an organism's natural defenses. They argue that, among other things, activated SIRT1 triggers changes in cells that mobilize repair mechanisms and increase energy production. It is, perhaps, these enhanced natural defense mechanisms that explain why animals on a calorie-restricted diet live longer and are healthier.

The idea that the genetic and molecular causes of aging and of many diseases are connected could provide a powerful new way of thinking about medicine, suggests Toren Finkel, a cardiologist at the National Heart, Lung, and Blood Institute in Bethesda, MD. Walk down the corridors of any hospital, he says, and you can't help but notice that many of the patients are elderly. "As cardiologists, we target what we view as causes of diseases -- clearly involved risk factors like hypertension." While that approach is effective, he says, it has largely ignored the most obvious factor in many diseases: age.

"It is obvious....We get sicker as we get older," says Finkel. He says he's not sure whether that observation "is so obvious it is stupid, or so obvious it is profound." But either way, he says, new research explaining the genetic and molecular events behind the aging process is, for the first time, raising the possibility of treating a broad range of diseases by intervening in that process. "No one had really thought about controlling aging as a practical way to control these diseases," says Finkel. "But it could be a powerful way of treating patients."

Our understanding of why people grow old is still primitive, but researchers say the drug discovery effort can push ahead regardless. "We don't understand a damn thing about aging," admits Helfand. But he's quick to add that the health benefits of calorie restriction are well documented in many organisms. And that, he says, "is very exciting from a drug discovery perspective."

The goal is clear: the discovery of drugs that will delay the onset of many of our most devastating diseases, the kind of illnesses that frequently turn the golden years into years of chronic ill health. "Everybody associates caloric restriction with longevity and life span, but the effects on diseases are much more immediate and important," says Guarente. "If only we understood how [calorie restriction] works, such knowledge would guide us in drug development. We would have a drug that would favorably impact many of the common diseases."

David Rotman is editor of Technology Review.

The Fountain of Health

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