A team of scientists report that the chemical resveratrol, commonly found in red wine, can help keep heart tissues young and delay aging—and at levels lower than previously expected, according to a study on mice released on June 4. The researchers found the health benefits at levels equivalent to three or four glasses of red wine a day in humans, but they believe that a glass of red wine a day might provide all the resveratrol the heart needs.
Previous studies have reported on resveratrol's beneficial effects, but the amounts typically used in the studies equalled the amount of resveratrol found in hundreds of bottles of red wine. Some scientists questioned the new findings and maintained that supplements with high doses of resveratrol potentially provide better results.
In the study, conducted at the University of Wisconsin-Madison, the researchers found that low doses of resveratrol added to the diets of middle-aged mice helped keep the hearts healthy by influencing the genetic levers responsible for aging.
"If someone is interested in obtaining the necessary levels of resveratrol through their diets alone, which includes a glass of red wine or two every day," said Tomas Prolla, a University of Wisconsin-Madison professor of genetics and study co-author, "then our conclusions strongly support that this amount of red wine will help prevent the heart from premature aging."
The question that now needs asking, Prolla said, is, "How low can you go with resveratrol and still see a benefit?"
In the study, published online in the open-access journal Public Library of Science ONE, the scientists split 60 mice into three equal groups, feeding one group a standard mouse diet, while another ate diets that restricted the total caloric intake by around 20 to 30 percent in order to initiate what is known as caloric restriction (CR). Previous research has found that a CR diet can slow aging in rodents by as much as 30 percent by triggering anti-aging activities in cells. The third group of mice ate standard diets supplemented daily—beginning in middle age, or 14 months—with 4.9 milligrams of resveratrol per kilogram of body weight.
According to Prolla, the study started under the assumption that resveratrol may work in ways similar to caloric restriction. "CR retards several aspects of the aging process in mammals, including age-related mortality, tumor genesis [and] physiological decline," the study reads. "The wide scope of these actions, and the profound metabolic and hormonal shifts induced by CR has led to efforts at identifying natural or synthetic compounds that mimic the effects of CR."
"Because most age-related diseases are likely to be secondary to the aging process itself, the discovery of such compounds could have a profound public health impact by reducing disease incidence and possibly extending the quality and length of the human lifespan," the study states.
After giving the mice resveratrol, the scientists performed a wide range of tests, most notably an electrocardiogram and in-depth genetic analysis. They found that the hearts of the mice on resveratrol stayed stronger and the tissue maintained its health for longer.
Perhaps more important, "Resveratrol opposed 947 (92 percent) of age-related changes in gene expression, and 522 of these represented highly significant differences in expression between the old control and old resveratrol groups," reported the study. Simply put, the resveratrol prevented changes in cells that lead to aging.
According to study co-author Richard Weindruch, a researcher at the William S. Middleton Memorial Veterans Hospital in Madison, the doses of resveratrol given to the mice amounted to between three to four glasses of red wine a day in a 154-pound person, once the differences in metabolic speed are taken into account (mice metabolize resveratrol approximately 10 times faster than people).
He believes that results similar to what was observed in the mice may be seen as low as one glass of wine. "All in all, things are pointing toward adequate resveratrol dosages being available by drinking a reasonable amount of red wine." However, clinical trials are necessary to establish or disqualify this link, he said.
"Thus, resveratrol at doses that can be readily achieved through dietary supplementation in humans is as effective as CR in opposing the majority of [gene-related] alterations in the aging heart," the study concluded.
Prolla says that he and Weindruch found that resveratrol at low doses works in ways different from earlier studies such as David Sinclair's research that found that resveratrol extends the life of artificially fattened mice by enhancing the activity of sirtuin enzymes, which are believed to play a role in anti-aging. In the new research, resveratrol did not affect the behavior of sirtuins. Nor did it prevent oxidative damage or stop tumor growth, both age accelerators, as other researchers found. "These studies used resveratrol in massive, unobtainable doses, perhaps to best develop a resveratrol pill," said Weindruch.
But other scientists questioned the low-dose findings and called for more research. Dr. John Auwerx of the Institute of Genetics and Molecular and Cellular Biology in Illkirch, France, who found in a 2007 study that mice given high doses of resveratrol were more physically fit despite high-fat diets, expressed doubts. "I would be really cautious, as we never saw significant effects with such low amounts," Auwerx told the New York Times.
The development of red wine-based pharmaceuticals is becoming big business, as Sinclair's company, Sirtris, completed its sale to GlaxoSmithKline for $720 million this week. Weindruch and Prolla also own a company, LifeGen Technologies, that is devoted to discovering the genetic process behind aging in order to both improve and extend human life.
For the record, Prolla is not a big red wine drinker, nor is Sinclair, with the latter preferring to take resveratrol supplements. Weindruch, on the other hand, likes to "do both," in order to have "clear biological activity to report."
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