As reported by The Hartford Courant, July 14, 2004.

In Wine, a Possible Key to a Long Life

By William Hathaway

Scientists seeking a molecular fountain of youth say they have found new evidence that they are at least on the right path.

Researchers from the University of Connecticut Health Center, the Harvard Medical School and Brown University report today in the science journal Nature that a compound found in red wine extends the life span of both worms and flies.

The report builds upon last year's findings by Harvard scientists that the compound resveratrol helps yeast live well beyond its normal life span. The scientists caution that the study doesn't mean that the compound is a longevity elixir. But they are more confident that any longevity drug developed would, like resveratrol, act on one of the molecular complexes activated by a lack of food.

Severely restricting calories has led to a longer life in all organisms studied so far.

"This opens up the pathway for biochemical and pharmacological interventions to slow aging and extend life span," said Stephen Helfand, professor of genetics and developmental biology at UConn and an author of the paper.

Blanka Rogina, an assistant professor at UConn, and researchers at Harvard wanted to see if resveratrol would have the same beneficial effects on flies and worms as it did in yeast.

The scientists were interested in the compound, found in small amounts in wine, because it is one of a family of compounds that activate a protein known as Sir2, which is involved in silencing genes and repairing DNA. Sir2 also appears to be a key player in why calorie restriction extends life. The protein exists in almost all species, including humans. Increased expression of Sir2 has been shown to dramatically increase life span in yeast and worms.

Worms and flies fed resveratrol lived an average of 30 percent longer than worms and flies that were not fed the compound. The importance of Sir2 was reaffirmed because when it was eliminated, flies and worms did not live longer even if they had been fed a diet of resveratrol.

Researchers had thought that the anti-oxidant properties of resveratrol gave it a protective effect against cell death, but now it appears that Sir2 is involved, Helfand said.

"Sir2 is the key. All roads go through Sir2," said Leonard P. Guarente, professor of biology at the Massachusetts Institute of Technology and a leading aging researcher.

Guarante noted that resveratrol may not be the most efficient way to activate the Sir2 system and increase longevity.

"It may be [another] compound we have yet to identify," said Guarante, a scientific founder of Elixir Pharmaceuticals, a biotechnology company that is trying to develop longevity drugs. "But it is starting to come together."

It is unclear why Sir2 seems to have such a protective effect. Guarante has shown that the protein is also involved in regulating fat development and other scientists have shown that Sir2 may depress the rate of apoptosis, or cell suicide.

The paper also reported that flies and worms fed resveratrol showed no decline in their ability to reproduce, even though calorie-restricted animals have all shown a reduced ability to produce offspring. Delaying reproduction makes evolutionary sense in times of famine, biologists say. However, Helfand says that it is possible - in the laboratory at least - to get the benefits of longevity without paying the price of reduced reproductive ability or having to go on a perpetual fast.

"Maybe we can make an acceptable payment," for longevity, Helfand said.