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The search for an antidote to aging has hit a snag. New research suggests that a natural substance once thought to extend lifespan may not be such a big deal after all. NPR's Jon Hamilton reports on the rise and fall of an idea that intrigued scientists and captivated the public.

JON HAMILTON: About a decade ago, scientists noticed that natural proteins called sirtuins seemed to help living things live longer. Then, in 2006, a Harvard researcher named David Sinclair reported that a substance thought to activate sirtuins actually did extend the lives of obese mice. The substance is called resveratrol and it's found in red wine. This is how Sinclair described its effect at the time.

DAVID SINCLAIR: The chance of dying was reduced about 30 percent. And the reason I can't tell you exactly how much longer they lived is the study's still going. We rushed it to publication because it was so dramatic.

HAMILTON: Sinclair's study was published in the journal Nature and reported by media around the world. The thinking was that if fat mice lived longer, so would thin, healthy mice. As a result, sales of red wine jumped and a biotechnology company co-founded by Sinclair became extremely valuable. The company, called Sirtris, was purchased by Glaxo Smith Kline in 2008 for $720 million.

But along the way, some scientists began questioning whether sirtuins really were the key to living longer. And this week, the journal Nature is publishing research that offers a strong rebuttal to that idea. The centerpiece is a study by a team including David Gems, a geneticist who studies aging at University College London. Gems says the team tried to replicate some of the early experiments with worms and fruit flies.

DAVID GEMS: We could create worms and flies with elevated levels of this sirtuin protein, and they were not long lived. So that implies that the sirtuin protein is not causing an increase in lifespan.

HAMILTON: Gems says some animals in the original studies had genetic mutations that made them live longer for reasons that had nothing to do with sirtuins. He says the new findings put sirtuins in a very different light.

GEMS: What this should do is act as a cap on the idea that they're important in the biology of aging. However, I suspect that the arguments will carry on for another year or two, with people who are very attached to the idea that they're important in aging.

HAMILTON: One of those people is Lenny Guarente from MIT. He did some of the key studies suggesting that sirtuins could extend life in both worms and fruit flies. He's also on the science advisory board at Sirtris.

Guarente has a new paper of his own in Nature that looks at whether his initial results with worms could have been affected by a mutation. He says they were.

LENNY GUARENTE: One strain did have a problem and so we redid everything and found that the basic conclusion of the paper stands. But the degree of extension of lifespan, we place now in the 10 to 15 percent range, rather than the 30 percent range.

HAMILTON: Guarente says he's not sure why Gems didn't find any life-extending effect. But Guarente adds that his goal has always been to find drugs that use the sirtuin system to prevent the diseases associated with aging, diseases like diabetes and heart disease. And he says in animals at least, sirtuin drugs have done just that.

GUARENTE: We're treating diseases. We're not treating aging itself. So I think that all this fuss about whether it's 10 percent or 15 percent or 30 percent extension in a roundworm is a bit of a tempest in a teapot.

HAMILTON: So even if sirtuins don't prevent aging, they might prevent disease. But this new thinking may be disappointing for healthy people hoping sirtuins would help them live longer.

Scott Pletcher is a geneticist at the University of Michigan who wrote an article that accompanies the new research in Nature. Pletcher agrees that sirtuin drugs may well turn out to have a role in preventing diseases.

SCOTT PLETCHER: But the concept of understanding the nature of aging and having that sort of be solved, that's what I think is sort of just blown apart.

HAMILTON: Pletcher says the new research also blows apart the idea that resveratrol, the substance in red wine thought to activate sirtuins, can extend life. The researchers included an experiment that found resveratrol didn't, in fact, activate those sirtuin proteins.

Jon Hamilton, NPR News.

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