Researchers discover the first compounds that slow aging across species

Three colleagues with a common interest in the biology of aging have determined that the compound resveratrol, an antioxidant found in red wine, can slow the aging process in yeast, fruit flies and nematodes. The three — David Sinclair of Harvard, Marc Tatar of Brown, and Stephen Helfand of the University of Connecticut — reported their findings in the July 15, 2004, issue of Nature.

From Brown University:
Researchers discover the first compounds that slow aging across species

Three colleagues with a common interest in the biology of aging have determined that the compound resveratrol, an antioxidant found in red wine, can slow the aging process in yeast, fruit flies and nematodes. The three — David Sinclair of Harvard, Marc Tatar of Brown, and Stephen Helfand of the University of Connecticut — report their findings in the July 15, 2004, issue of Nature.

Last July, during a day trip to Boston, Brown biologist Marc Tatar popped into the lab of David Sinclair, a friend and pathology researcher at Harvard Medical School.

Tatar and Sinclair share a fundamental fascination: how and why living organisms age. Tatar experiments with fruit flies. Sinclair works with yeast — and he wanted to share an interesting find. Sinclair put a teaspoonful of clear liquid in a vial and placed it in a box of ice. He handed the box to Tatar and said, ”We think it’s safe. Try it out.”

Tatar, an associate professor in the Department of Ecology and Evolutionary Biology, was intrigued. Back at Brown, he cooked the compound into a sweet corn meal mush, fed his flies and waited. He was amazed. The flies lived longer — some nearly 30 percent longer — than the average Drosophila melanogaster.

This discovery prompted an unusual, three-university experiment that has netted a true scientific breakthrough: the discovery of the first compounds that slow aging across species. The results are published in the July 15, 2004, issue of Nature.

”To work across species, the mechanism behind how these compounds function must be very, very old — predating the evolution of yeast,” Tatar said. ”It’s amazing stuff.”

The compound Sinclair gave Tatar was resveratrol, an antioxidant found in red wine. To put resveratrol to a more rigorous, far-reaching test, Tatar and Sinclair enlisted Stephen Helfand, a researcher at the University of Connecticut.

The trio tested resveratrol along with fisetin, a close cousin in its plant-based family. They fed the compounds to yeast, worms and flies. Results showed that molecules called sirtuins slowed aging in all organisms. Flies, for example, live an average of 43 days. But flies that ate resveratrol lived up to 51 days. Flies that ate fisetin lived as long as 53 days.

Why? Sirtuins mimic the life-extending effects of caloric restriction, a biochemical cascade known to slow aging in mammals. Scientists don’t fully understand why caloric restriction prolongs life. Tatar said the best thinking is this: Living creatures are hard-wired to reproduce. But a severe, low-calorie diet trips physiological sensors, sending a message throughout the body that conditions aren’t ripe for reproduction. Cellular defense systems go up and aging slows, preserving the body for better, more reproduction-friendly times.

”In this case, a little stress is actually beneficial,” Tatar explained. ”It’s evolution.”

What was startling about the experiment is that sirtuins don’t extend life when coupled with real caloric restriction. In fact, when flies on a low-calorie diet ate resveratrol and fisetin, they didn’t live any longer than average flies. Another surprising discovery was the fact that flies feasting on sirtuins didn’t have problems reproducing — a negative side effect of caloric restriction.

One practical application of the research is in prescription drug development. But Tatar said a ”Ponce de Leon pill” won’t be found in pharmacies any time soon. Because sirtuins dissipate quickly in the blood, Tatar predicted that it would take scientists at least five years to create compounds stable enough for use in drugs.

Consumers shouldn’t expect a silver-bullet centenarian pill. ”We’d probably see these compounds used in drugs that target a specific age-related disease, such as diabetes or heart failure,” he said. ”If those diseases are delayed, we’d live longer.”


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