3:17pm

Wed September 21, 2011
The Salt

What's In That Wine Glass May Not Prevent Aging After All

Originally published on Wed September 21, 2011 5:43 pm

If you've been counting on your daily dose of merlot to stave off mortality, you might want to consider Plan B.

The links between red wine and longevity aren't nearly as strong as they once seemed, according to new research in the journal Nature. In fact, the research calls into question the whole mechanism used to explain wine's power to extend life.

Sorry, oenophiles.

This all has to do with some natural proteins called sirtuins. (That's pronounced sir-TWO-ins in American English, in case you're reading this out loud at a bar.) Yeast carry a version. So do worms, mice and people.

About 10 years ago, scientists noticed that an extra helping of sirtuins seemed to help living things live longer. And there was some evidence that a substance in red wine called resveratrol could crank up sirtuin production.

Then, in 2006, a Harvard researcher named David Sinclair reported that obese mice that got doses of resveratrol lived longer than fat mice who didn't — about 30 percent longer.

The study was published in Nature and reported by media around the world. The assumption was that what was good for fat mice would also be good for thin animals, or even people.

As a result, sales of red wine jumped and a biotechnology company founded by Sinclair and others to develop the substance as a drug became extremely valuable. In 2008, the drug company GlaxoSmithKline bought Sinclair's company, Sirtris, for $720 million.

But over the years, some scientists had begun to question whether sirtuins really were the key to extending life. Some studies of sirtuins even suggested they didn't affect lifespan.

And this week, Nature published research that offers a strong rebuttal to the idea.

The centerpiece is a study by a team including David Gems, a geneticist who studies aging at University College London. The team attempted to replicate some of the early experiments with worms and fruit flies.

"We could create worms and flies with elevated levels of this sirtuin protein," Gems says. But, he adds, "They were not long-lived."

The reason that animals in the original studies lived longer, Gems says, is that they had genetic mutations that had nothing to do with sirtuins. And this puts the proteins in a very different light, he says.

"What this should do is act as a cap on the idea that they are important in the biology of aging," Gems says.

It also "blows apart" the idea that scientists have figured out the nature of aging, says Scott Pletcher a geneticist at the University of Michigan who wrote an article that accompanies the new Sirtuin research in Nature.

Some of the researchers who did the early work on sirtuins disagree with that conclusion. But they concede that there were genetic changes in some of the animals in those early studies.

"One strain did have a problem and so we redid everything," says Leonard Guarente from MIT, who is on the science advisory board of Sirtris.

When that strain was removed from the results, Guarente says, sirtuins still produced a life-extending effect, but it was "in the 10 to 15 percent range rather than the 30 percent range."

People shouldn't give up on sirtuin drugs though — especially people who eat too much, or have a high-fat diet, Guarente says.

He says a primary goal of the research on sirtuins was to develop drugs that could prevent diseases associated with aging, like diabetes and heart disease. As a result, many of the experiments have looked at drugs that affect sirtuins in animals that are obese or eat a lot of fat.

And those studies show that sirtuin drugs do make a difference, Guarente says.

"We're treating diseases," he says. "We're not treating aging itself."

Other scientists agree that sirtuin drugs do show promise in preventing diseases in high-risk individuals. In theory, that could mean drugs that would let you eat fatty foods or get fat without putting your life at risk.

But it's unlikely that red wine will help by activating sirtuins.

The new research in Nature includes an experiment that tested the supposed active ingredient in red wine: Resveratrol. The researchers found that resveratrol had no effect on sirtuins.

We have no doubt we haven't reached the bottom of the bottle on this one.

Copyright 2013 NPR. To see more, visit http://www.npr.org/.

Transcript

MELISSA BLOCK, Host:

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. Transcript provided by NPR, Copyright NPR.