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Molecules that could slow aging found

Go ahead, have a glass of merlot -- and maybe top it off with some peanut butter and mulberries while you're at it.

Harvard Medical School scientists have identified a group of molecules that lengthen the lives of yeast cells by as much as 80 percent. The life-extending substances are found in red wine, peanuts, and certain plants, fruits and vegetables.

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The researchers described the results as a potential breakthrough, which could lead to the development of drugs that could drastically extend human life- span and treat aging-related disorders such as stroke and Alzheimer's disease.

"This is the first time that slowing down human aging looks like a real possibility rather than science fiction," said Harvard molecular geneticist David Sinclair, who co-wrote the study. "This may be a turning point for humans."

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The researchers found a way to stimulate sirtuins, a class of enzymes that seems to help cells repair damage. Sirtuins are found in all living organisms except viruses. Humans have seven types of sirtuins. Published in the latest issue of Nature, the study identified 17 sirtuin-stimulating chemicals.

When yeast cells were exposed to small doses of these chemicals, known as polyphenols, the cells lived significantly longer than normal.

Many polyphenols are powerful anti-oxidants that protect cells from the harmful effects of certain oxygen molecules. But the life-extending benefits Sinclair found were not caused by the chemicals' anti-oxidant properties, he said.

The most powerful of these sirtuin-activating compounds (STAC) is a substance called resveratrol, which is found in mulberries, peanuts and especially in red wine. Yeast cells injected with resveratrol lived up to 80 percent longer than normal.

"That's the most exciting molecule we've found," Sinclair said. Since making the discovery, he has increased his red wine consumption, drinking about a glass a day. Before that, he had perhaps a glass a month.

The researchers have done preliminary work on the effect of STACs on humans. In an experiment on human cells, Sinclair found that resveratrol boosted a specific sirtuin enzyme. Cells treated with resveratrol were more than three times as likely to survive radiation as untreated controls.

The researchers are now looking at how STACs affect worms and flies. Sinclair says the early results are promising.

'Big leap'

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Some scientists expressed skepticism that these benefits could be transferred to humans. "It's great if you're a yeast. But it's a big leap from a yeast cell to a human," said Merck researcher Mark Lane, who studies aging in monkeys.

"It's intriguing. But will it work in people? We don't know," said David Finkelstein, a program manager at the National Institute on Aging, which funded Sinclair's study.

Diet similarity

Sirtuins seem to work by allowing injured cells more time to repair themselves before they die. Sinclair and his collaborators say sirtuin activators work via the same biochemical pathway as calorie restriction, a Spartan diet that has been shown to increase lifespan in a range of animals, including yeast, rats and other mammals.

"We think we've found something that chemically mimics calorie restriction," says molecular biologist Konrad Howitz, who co-wrote the study with Sinclair.

But Lane, who is working on an elaborate study of the diet regimen's effect on 120 rhesus monkeys, said that calorie restriction may not work by the same pathways in yeast and more complex animals: "Humans don't die of the same things that yeast do."

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Even if Sinclair's results can be applied to humans, that payoff is probably decades away, Lane said.

Howitz, who works for BIOMOL, a biotechnology company in suburban Philadelphia, disagreed, arguing that yeast's "longevity pathway" is similar to that of multicellular organisms. This resemblance probably extends to humans, he said. "Yeast is closer to humans than most people realize," he said.

BIOMOL and Sinclair have also created synthetic STACs that are more powerful and stable than the naturally occurring compounds. When exposed to oxygen, for example, the res- veratrol in red wine breaks down within hours.

These synthetic compounds could eventually be used to fight aging and a range of diseases, Sinclair said. He offered one example of how these sirtuin-activating drugs might work: "In stroke, brain cells die because they lack oxygen. If people were injected with these drugs, the cells could survive longer."

Research on aging

The study is part of a new trend in aging research. In recent years, a small group of scientists have turned away from looking for the cause of aging and focused instead on finding ways to slow the process.

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Sinclair is planning a study that looks at the compounds' effects on mice. If STACs are found to be safe and effective in these animals, human trials might begin within five years, he said.

Finkelstein, however, said that less drastic life-extension methods exist.

"You want to live a long life? Eat a healthy diet, keep active, exercise your mind," he said. "Don't smoke. And don't get run over by a car. We know for sure that all of those things work."

For the record

An article in Monday's Sun on discoveries about aging omitted the proper affiliation of researcher Mark Lane. His work on monkeys' lifespans was conducted at the National Institute on Aging.The Sun regrets the errors.


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