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How do the French get away with a clean bill of heart health despite a diet loaded with saturated fats? Scientists have long suspected that the answer to the so-called "French paradox" lies in red wine. Now, the results of a new study bring them closer to understanding why.

Writing this week in the online, open-access journal Public Library of Science (PLoS) ONE, researchers from industry and academia, including the University of Wisconsin-Madison and the University of Florida, report that low doses of resveratrol — a natural constituent of grapes, pomegranates, red wine and other foods — can potentially boost the quality of life by improving heart health in old age.

The scientists included small amounts of resveratrol in the diets of middle-aged mice and found that the compound has a widespread influence on the genetic causes of aging. Specifically, the researchers found that low doses of resveratrol mimic the heart-healthy effects of what is known as caloric restriction, diets with 20 to 30 percent fewer calories than a typical diet. The new study is important because it suggests that resveratrol and caloric restriction, which has been widely studied in animals from spiders to humans, may govern the same master genetic pathways related to aging.

"Caloric restriction is highly effective in extending life in many species. If you provide species with less food, the regulated cellular stress response of this healthy habit actually makes them live longer," says study author Christiaan Leeuwenburgh, Ph.D., chief of the division of biology of aging at UF's Institute on Aging. "In this study, the effects of low doses of resveratrol (on genes) were comparable to caloric restriction, the hallmark for life extension."

Previous research has shown that high doses of resveratrol extend life in invertebrates and prevent early death in mice given a high-fat diet. The new study extends those findings, showing that resveratrol in low doses, beginning in middle age, can elicit many of the same benefits as a reduced-calorie diet.

"Resveratrol is active in much lower doses than previously thought," said Tomas Prolla, a UW professor of genetics and a senior author of the new report.

The group explored the agent's influence on the heart, muscle and brain by looking to see which genes were switched on and off during the aging process.

In the new study — which compared the genetic responses of animals to either restricted diets or normal diets including small doses of resveratrol — the similarities were remarkable, explains lead author Jamie Barger of Madison, Wis.-based LifeGen Technologies, who spearheaded the research.

In the heart, for example, there are at least 1,029 genes whose functions change with age. In animals on restricted diets, 90 percent of those heart genes experienced alterations in gene expression, while low doses of resveratrol thwarted age-related change in 92 percent. The new findings, say the study's authors, reveal how red wine's special ingredient helps keep the heart young.

In short, the authors note that a glass of wine or food or supplements containing even small doses of resveratrol are likely to help stave off cardiac aging.

That finding, may also explain the remarkable heart health of people who live in some regions of France where diets are soaked in saturated fats but the incidence of heart disease, a major cause of mortality in the United States, is low. In France, meals are traditionally complemented with a glass of red wine.

"There must be a few master biochemical pathways activated in response to caloric restriction, which in turn activate many other pathways," explained Prolla. "And resveratrol seems to activate some of these master pathways as well."

Resveratrol is currently sold over-the-counter as a nutritional supplement with supposed anti-cancer, anti-viral, anti-inflammatory and anti-aging benefits, although few scientific studies have verified these claims in humans. That may soon change: Researchers at the University of Florida hope to explore the effects of resveratrol on older people in a phase 1 clinical trial, set to begin this summer.

The study will assess the supplement's effects on memory, physical performance, inflammation and oxidative damage, according to Steve Anton, Ph.D., a principal investigator of the upcoming trial and an assistant professor of aging and geriatrics in the UF College of Medicine.

Mitochondria, the tiny power plants that keep a cell functioning, are especially vulnerable to the oxidative damage that accumulates during the aging process.

"In animal studies, (resveratrol) seems to promote mitochondrial health," said Todd Manini, Ph.D., also a principal investigator of the upcoming trial and an assistant professor of aging and geriatrics in the UF College of Medicine. "Mitochondria are everywhere: They're in the brain, in the muscle, the liver. So it could have kind of a global impact on many different organ systems."