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A component of red wine recently shown to help laboratory mice live longer also protects animals from obesity and diabetes, researchers reported Thursday.
The new research helps confirm and extend the possible benefits of the substance, resveratrol, and offers new insight into how it works -- apparently by revving up the metabolism to make muscles burn more energy and work more efficiently. Mice fed large doses could run twice as far as normal.
In addition, the scientists produced evidence for the first time linking the biological pathway activated by the substance to humans, showing that the same genetic switch that resveratrol mimics seems to naturally endow some people with faster metabolisms.
"It's very exciting," said Johan Auwerx, professor of medicine at the Institute for Genetics and Cellular and Molecular Biology in Strasbourg, France, who led the research, which is being published in the journal Cell. "This compound could have many applications -- treating obesity and diabetes, improving human endurance, helping the frail. There's a lot of potential."
Auwerx and other researchers cautioned that much more research is needed to study the compound and similar agents, especially to see if the approach is safe for people. Humans would have to take hundreds of resveratrol pills sold in health food stores or drink hundreds of glasses of wine a day to get equivalent levels of the substance tested on the mice, neither of which would be safe.
But the new research adds to growing enthusiasm about the approach, experts said.
"This is the first example of a drug that can apparently affect the whole aging process, not just this disease or that disease, but the mechanisms that allow these diseases to occur," said Felipe Sierra of the National Institute on Aging.
Others agreed.
"The idea of giving someone anything to improve their longevity until very recently would have been considered snake oil or crockery," said Stephen Helfand of Brown University. "But here we are, possibly being able to move out of the laboratory from extending the lives of flies, worms and mice to humans, a lot sooner than we thought."
Resveratrol is found in red wine, grapes and other foods, including peanuts. Scientists suspect it may help explain why French people have fewer heart attacks despite their high-fat diets, and why eating a very low-calorie diet can lengthen the lives of many species.
Researchers recently demonstrated that resveratrol did the same thing for mammals in a study involving laboratory mice. High doses of the compound neutralized the ill effects of a high-fat, high-calorie diet, extending the animals' lives and preventing harm to their livers and hearts.
In the new study, researchers fed mice even higher dosages -- 10 times higher -- along with a high-fat, high-calorie diet. Resveratrol significantly reduced the animals' chances of becoming obese and of developing early signs of diabetes. The mice appeared to experience no harmful side effects.
Additional experiments on the animals' cells indicate the substance works by increasing the activity of an enzyme known as SIRT1, boosting the number and activity of structures inside cells called mitochondria, the researchers said. Mitochondria are like power plants inside cells, burning fat and providing energy. They tend to get revved up by exercise and to deteriorate with age.
The mice fed resveratrol had more efficient muscle tissue, sharply improving their endurance.
"In the elderly, many of the disorders that occur with aging occur because of muscle weakness," Helfand said. "This makes you wonder what would happen if you took an older individual and revved up their mitochondria with resveratrol. You could imagine that it could have a profound positive effect on their health."
Auwerx also wondered whether the substance might be abused by professional athletes. "That could be the illicit use of these compounds -- as performance boosters," he said.
In addition to the mouse experiments, the researchers also produced evidence supporting the theory that SIRT1 plays a key role in longevity in humans in an accompanying analysis of 123 Finnish adults. The subjects born with certain variations of the SIRT1 gene had faster metabolisms, naturally burning energy more efficiently, indicating the same pathway works in humans, too.
"We've all seen people who are thin no matter what they eat or do -- that have good metabolisms versus bad. This may help explain that," said Christoph Westphal, chief executive of Sirtris Pharmaceuticals of Cambridge, Mass., which sponsored and helped conduct the study as part of its effort to develop drugs based on the approach.
The company is already testing a potent version of resveratrol on diabetic humans and hopes to eventually test it and similar compounds as a treatment for a variety of diseases. "We are targeting a gene that controls the aging process," Westphal said. "Many diseases have a link to the aging process. So these kinds of drugs clearly have the potential to treat several diseases of aging."
Other researchers said the new work is interesting but remained cautious, particularly about making the link to SIRT1.
"I think that's part of the story, but that it would be a mistake to think that's all that's going on," said Matt Kaeberlein of the University of Washington.
The new research helps confirm and extend the possible benefits of the substance, resveratrol, and offers new insight into how it works -- apparently by revving up the metabolism to make muscles burn more energy and work more efficiently. Mice fed large doses could run twice as far as normal.
In addition, the scientists produced evidence for the first time linking the biological pathway activated by the substance to humans, showing that the same genetic switch that resveratrol mimics seems to naturally endow some people with faster metabolisms.
"It's very exciting," said Johan Auwerx, professor of medicine at the Institute for Genetics and Cellular and Molecular Biology in Strasbourg, France, who led the research, which is being published in the journal Cell. "This compound could have many applications -- treating obesity and diabetes, improving human endurance, helping the frail. There's a lot of potential."
Auwerx and other researchers cautioned that much more research is needed to study the compound and similar agents, especially to see if the approach is safe for people. Humans would have to take hundreds of resveratrol pills sold in health food stores or drink hundreds of glasses of wine a day to get equivalent levels of the substance tested on the mice, neither of which would be safe.
But the new research adds to growing enthusiasm about the approach, experts said.
"This is the first example of a drug that can apparently affect the whole aging process, not just this disease or that disease, but the mechanisms that allow these diseases to occur," said Felipe Sierra of the National Institute on Aging.
Others agreed.
"The idea of giving someone anything to improve their longevity until very recently would have been considered snake oil or crockery," said Stephen Helfand of Brown University. "But here we are, possibly being able to move out of the laboratory from extending the lives of flies, worms and mice to humans, a lot sooner than we thought."
Resveratrol is found in red wine, grapes and other foods, including peanuts. Scientists suspect it may help explain why French people have fewer heart attacks despite their high-fat diets, and why eating a very low-calorie diet can lengthen the lives of many species.
Researchers recently demonstrated that resveratrol did the same thing for mammals in a study involving laboratory mice. High doses of the compound neutralized the ill effects of a high-fat, high-calorie diet, extending the animals' lives and preventing harm to their livers and hearts.
In the new study, researchers fed mice even higher dosages -- 10 times higher -- along with a high-fat, high-calorie diet. Resveratrol significantly reduced the animals' chances of becoming obese and of developing early signs of diabetes. The mice appeared to experience no harmful side effects.
Additional experiments on the animals' cells indicate the substance works by increasing the activity of an enzyme known as SIRT1, boosting the number and activity of structures inside cells called mitochondria, the researchers said. Mitochondria are like power plants inside cells, burning fat and providing energy. They tend to get revved up by exercise and to deteriorate with age.
The mice fed resveratrol had more efficient muscle tissue, sharply improving their endurance.
"In the elderly, many of the disorders that occur with aging occur because of muscle weakness," Helfand said. "This makes you wonder what would happen if you took an older individual and revved up their mitochondria with resveratrol. You could imagine that it could have a profound positive effect on their health."
Auwerx also wondered whether the substance might be abused by professional athletes. "That could be the illicit use of these compounds -- as performance boosters," he said.
In addition to the mouse experiments, the researchers also produced evidence supporting the theory that SIRT1 plays a key role in longevity in humans in an accompanying analysis of 123 Finnish adults. The subjects born with certain variations of the SIRT1 gene had faster metabolisms, naturally burning energy more efficiently, indicating the same pathway works in humans, too.
"We've all seen people who are thin no matter what they eat or do -- that have good metabolisms versus bad. This may help explain that," said Christoph Westphal, chief executive of Sirtris Pharmaceuticals of Cambridge, Mass., which sponsored and helped conduct the study as part of its effort to develop drugs based on the approach.
The company is already testing a potent version of resveratrol on diabetic humans and hopes to eventually test it and similar compounds as a treatment for a variety of diseases. "We are targeting a gene that controls the aging process," Westphal said. "Many diseases have a link to the aging process. So these kinds of drugs clearly have the potential to treat several diseases of aging."
Other researchers said the new work is interesting but remained cautious, particularly about making the link to SIRT1.
"I think that's part of the story, but that it would be a mistake to think that's all that's going on," said Matt Kaeberlein of the University of Washington.
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