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Substance in Red Wine Extends Life Span of Organisms

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PHILADELPHIA - Could the fountain of youth be red?

A compound found in red wine - and to a lesser extent in peanuts - extends the life span of yeast cells by about 80 percent, researchers have found.

Whether the substance, known as resveratrol, has the same effect on humans remains to be seen. But the early findings have sparked widespread interest in the compound and the Plymouth Meeting, Pa., scientists behind the research.

Ira Taffer and Robert Zipkin weren't looking for anti-aging miracles 20 years ago when, fresh out of Drexel University, they started a company called BIOMOL Research Laboratories Inc. But their work veered in that direction this year when they discovered that resveratrol staved off aging and death in simple organisms.

"What's really astonishing about this study is they were able to extend the life span of these organisms," said Jef Boeke, a yeast geneticist from Johns Hopkins University. People have been able to extend animal life spans through genetic manipulation and other extreme means, but never before by a drug-like substance.

Taffer, Zipkin and BIOMOL's director of molecular biology Konrad Howitz collaborated with Harvard University. They released their results electronically last month and will officially publish the findings in this week's issue of the journal "Nature."

Will this lead to anti-aging pills?

"This research makes it a real possibility we'll see those in our lifetime," Boeke said.

No one knows how much resveratrol - or wine - it would take to have a similar effect in humans. Some earlier research shows that resveratrol has anti-cancer properties, though other studies show that alcohol increases risk for some cancers.

The BIOMOL team members agree that resveratrol is unlikely to make people live to 160, but they say it's worth further investigation. Yeast cells and human cells share similar architecture and function, the researchers say, and if the substance has such a profoundly positive effect on the yeast cells, it might do something in people - perhaps offer protection against a major disease associated with aging, such as Alzheimer's disease.

Before its newfound fame, BIOMOL, housed in a low brick building in a narrow suburban cul-de-sac, was doing a brisk business making chemical tools used by medical researchers. The company specialized in making certain kinds of tests that signal the presence of various biological compounds.

Those were tools Harvard researcher David Sinclair needed. Sinclair was studying aging and had begun to concentrate on the role played by a class of enzymes called sirtuins.

A few years ago, another researcher, MIT's Leonard Guarente, discovered the importance of these enzymes while tinkering with the genetics of worms, trying to find ways to make them live longer. He found that he could make them live nearly twice as long by adding copies of a gene that held the code, or recipe for sirtuins.

Sinclair and others later found that sirtuins were involved in a puzzling effect that had been known for some time: that mice and other animals lived longer if kept on a very low-calorie diet.

It turned out that near-starvation was sending the animal sirtuins into overdrive. They were working harder at a particular chemical task, snipping off a bit of another protein, which fed into some other link in a chain of reactions that involved the production of energy from food.

Sinclair started looking for an easier way to increase the activity of these sirtuins.

First, he needed a good test to measure sirtuin activity, and he turned to BIOMOL. Zipkin said they had a test for a more general class of enzymes and they were able to refine that for sirtuins.

In the course of this project, Zipkin decided to use the test on substances he thought might influence sirtuin activity. He found two chemicals that dramatically increased it.

"It was a Eureka moment," Zipkin said.

He said he realized that these substances both shared similar chemical structures to resveratrol, a component of red wine. "This already had a reputation," he said for health-giving properties.

At Harvard, Sinclair tested the resveratrol on his yeast cells and found it worked as well as starvation for extending their lives. The BIOMOL scientists say another researcher has found similar results in fruit flies but has not yet published his findings.

Howitz, Zipkin and Taffer say they realized they might be able to make and sell resveratrol as a supplement, once further testing showed it worked in laboratory animals such as mice. But others already have, Zipkin said, holding up a white plastic bottle labeled resveratrol - an herbal supplement extracted from a plant called Japanese knotweed.

Zipkin says that when they repeated their experiment trying to activate the sirtuins using the health-food company product, they got no effect whatsoever. He said a chemical analysis revealed that the supplements contained much less resveratrol than stated on the label.

A quick Internet search revealed a handful of other companies that have pounced on these new results to promote sales of resveratrol supplements. A company called "Young Again Nutrients" quoted headlines such as "red wine molecule extends life" to hawk red wine extracts.

John Pezutto, a Purdue University researcher who first discovered resveratrol's anti-cancer properties and published his findings in the journal "Science" in 1997, said that he gets his from a Canadian company called Royalmount Pharma, which he believes also manufactures reliable supplements using a synthetic version of the compound.

As for red wines, Pezutto said they vary in the amounts - some red wines carry almost no resveratrol. He said grapes can be grown under special conditions to increase their resveratrol content, or could be genetically engineered to become a richer source.

Should doctors start advocating a glass of red wine a day? Various studies point to cardiovascular benefits from small amounts of wine, but there's no shortage of evidence of the downsides of alcohol consumption - liver damage, links to some cancers, and alcoholism. There isn't any good evidence yet that the dose of resveratrol found in red wine would make a difference in human aging.

Many oenophiles point to the "French paradox," that the French enjoy better cardiovascular health than Americans despite eating more butter, cream and other rich food. Some credit the French affinity for red wine, though alternative explanations abound: The saturated fats in meat and butter turn out to be less harmful that the "transfats" in margarine and processed foods; the French eat smaller portions; they walk more; obesity is less prevalent.

Zipkin said his company is looking for a compound that works even better than resveratrol, something they might try to get into clinical trials. "But that will take years," he said.


(c) 2003, The Philadelphia Inquirer. Distributed by Knight Ridder/Tribune News Service.

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