Sinclair’s basic claim is simple, if seemingly improbable: he has found an elixir of youth.

In his Australian drawl, the 38-year-old Harvard University professor of pathology explains how he discovered that resveratrol, a chemical found in red wine, extends life span in mice by up to 24 percent and in other animals, including flies and worms, by as much as 59 percent.

Sinclair hopes that resveratrol will bump up the life span of people, too. “The system at work in the mice and other organisms is evolutionarily very old, so I suspect that what works in mice will work in humans,” he says.

Sinclair thinks resveratrol works by activating SIRT1, a gene that many scientists believe plays a fundamental role in regulating life span in animals.

(((Weird idea. No, he’s not kidding. Yes, he has big lab resources from wealthy backers.)))

While Sinclair was in Guarente’s lab in the late 1990s, he discovered that sir2 prevents aging in yeast by slowing down the accumulation of ERCs, circular strands of DNA that build up in organisms as they age, eventually killing them.

Around the same time, others in Guarente’s lab made another crucial discovery: that a link may exist between sir2 and a molecule critical for metabolizing food, called NAD. The connection suggested that the longevity gene might be related to diet–specifically, Guarente postulated, to caloric restriction.

A nutritionally complete diet containing 30 to 40 percent fewer calories than normal had long been known to extend life span in some animals, ramping up cell defenses and slowing down aging.

Guarente and others theorize that in times of scarcity, such as famine or drought, this mechanism allows an organism to survive–and postpone reproduction–until the crisis is over. The link between sir2 and NAD, therefore, suggested to Guarente that caloric restriction might be affecting longevity by activating the antiaging gene. (((See, it doesn’t rebuild you or anything ambitious — it’s just triggering an ancient system that’s already in there.)))

In a 2004 Science interview, Sinclair added to his reputation as a zealot, calling resveratrol “as close to a miraculous molecule as you can find.” “One hundred years from now,” he said, “people will maybe be taking these molecules on a daily basis to prevent heart disease, stroke, and cancer.”

Sinclair’s paper came out within days of a study in Cell from the lab of Johan Auwerx of the Institute of Genetics and Molecular and Cellular Biology in Illkirch, France. ­Auwerx’s team, which was partially funded by Sirtris ­(Auwerx is on the company’s scientific advisory board), had given mice even higher doses of resveratrol–400 milligrams per kilogram.

These mice stayed slender and strong on a high-fat diet, with the energy-charged muscles and reduced heart rate of athletes. The number of mitochondria in their cells increased, which improved the cells’ energy output.

Students in Sinclair’s lab say he sometimes seems driven, and he admits that he is: “I’m driven to get to goals as fast as possible. It frustrates people in my lab who have something they think is cool, but if it doesn’t move us forward, I don’t want to do it.” He says he views all the experiments being done at Sirtris, all his work, as part of a master plan. “I see this laid out in my mind, every step. But it’s happening faster than I imagined–it’s taking 10 years instead of 20 years.”

“When will it be ready for humans?” I ask.

“This will impact humans within a decade,” he says. “That’s why I don’t think there is anything more important than this quest. That’s why I take chances, and why the controversy is worth it: because I think we are right.”


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Date: 10 Jan 2011 | Author: mesmerX | Category: News | Views: 13113

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