Red Wine Molecule Negates Adverse Effects of a High-Fat Diet, Prolongs Life of Lab Mice

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Resveratrol may be able to prolong the healthy lifespan by 31 percent. Balance and coordination improved in lab animals as they aged.

aging is no longer an unsolved problem in biology

If the results of a just-completed animal study can be applied to humans, it may be possible for humanity to avert the harmful effects of high-calorie/high fat diets that now plague modern societies. The discovery announced today in Nature Magazine could be a timely intervention for human populations that overeat and consume excessive amounts of fat and sugar. Furthermore, humanity just may be another step closer to proving it is on the threshold of discovering a molecule that may significantly extend human life, or what some call an anti-aging pill.

Survival despite a bad diet

Researchers at a National Institutes of Aging laboratory in Baltimore were peering into cages of two groups of mice 26 weeks after they had begun eating a high-fat diet. The animals had started on their controlled diets at 52 weeks of age. Lab mice normally live 2-2.5 years (104-130 weeks). Now, 76 weeks into the study, 22% of the animals in one cage had died while none of the animals in the other cage were dead. The difference was striking, like no other similar experiment. What made the difference – the second group of mice had a molecule called resveratrol added to their fat-laden chow. At 107 weeks into the study, half of the animals on a high-fat diet had died compared to less than a third of the high-fat plus resveratrol-treated mice.

Dr. David Sinclair, Associate Professor of Pathology at Harvard Medical School and director of the Paul F. Glenn Laboratories for the Biological Mechanisms of Aging, led a team of researchers from the National Institute on Aging and Johns Hopkins University School of Medicine in Baltimore, as well as investigators from Australia and Spain, in making this discovery, published in Nature Magazine.

Calorie restriction mimic

Calorie restriction prolongs the life of most life forms. The molecule Sinclair used in the laboratory study is believed to mimic the effects of a low calorie diet without actually being deprived of food. The report concludes that "resveratrol can alleviate the negative impact of a high calorie diet on overall health and lifespan, without the animals having to undergo weight loss."

In the experiment, resveratrol switched on an array of genes that are also activated by calorie restriction. It is known that human populations that restrict their calorie intake, like adults on the Japanese island of Okinawa, experience exceptional health and longevity.

The mice on the high-fat diets, with or without resveratrol, experienced no significant difference in body weight or circulating cholesterol numbers. However, resveratrol did profoundly control blood sugar, appeared to improve balance and physical coordination as the animals aged, and maintained healthy liver tissue as well as prolonging their lifespan.

Resveratrol, which is found naturally in grapes, mulberries, peanuts and 70 species of other plants, is concentrated in the process of making wine, leading researchers to believe this molecule may be the primary reason for the reported health and longevity of the French, despite their high-calorie/high-fat diet. This phenomenon has been called "The French Paradox."

Slow the rate of aging

Researchers are saying that "aging is no longer an unsolved problem in biology" and the rate of aging can now be controlled. (Annals New York Academy Science 1067: 1-9, May 2006) Earlier this year researchers at the National Institute on Aging declared that the study of molecular mimics of calorie restriction is "an emerging research field." (Aging Cell 2006 Apr;5(2):97-108)

Other researchers indicate small molecules, like resveratrol, which are easily absorbed, can pass through cells walls, and can enter the genetic machinery in the cell nucleus, are "the future of regenerative medicine." (Current Topics Medicinal Chemistry 5: 383-95, 2005)

Correlates with prior studies

Prior studies, moving up the biological ladder from simple to more complex forms of life (yeast cells, fruit flies, roundworms, fish, and now mice), have shown that resveratrol prolongs life. This may be the closest biologists get to proving a molecule has life-extending effects in humans since a primate study would take 30-40 years and be very costly. Controlled human longevity studies would have to last 80-100 years before any conclusive data would be available.

While long-term human studies employing calorie restriction mimics would be unlikely to ever take place, based upon a growing body of evidence in other species that calorie restriction and its molecular mimics improve health and extend life, researchers at the National Institute on Aging say "we may never know for sure" but the best available evidence now suggests "we think so." (Biogerontology May, 27, 2006, early online report)

Dietary supplements or drugs?

The mouse/resveratrol study dispels earlier reports that orally consumed resveratrol is not biologically available. Two doses of resveratrol were employed in the study, equivalent in humans to 350 and 1540 milligrams for a 160-pound (70 kilos) human. The published results of the study involved the higher dose, which produced more pronounced effects.

Resveratrol from dietary supplements may not be equivalent to what researchers used in the laboratory test. Research-grade trans resveratrol was employed in the study (99% trans resveratrol, preserved in opaque, airtight, frozen vials). Upon exposure to light, heat or oxygen, trans resveratrol may convert to the less biologically active form, cis resveratrol, which does not activate the Sirtuin 1 gene, believed to be responsible for its beneficial health effects.

One manufacturer of dietary supplements (Longevinex®) has shown that botanical sources of trans resveratrol, encapsulated in airtight capsules (Licaps®, Capsugel®) and never exposed to light, heat or oxygen during manufacturing, maintains its molecular integrity for up to 2 years of shelf life and that significant amounts of resveratrol in conventionally-made pills may undesirably convert from trans to cis resveratrol and their labeled dosage may not be accurate.


Dr. David Sinclair of Harvard Medical School leads Sirtris Pharmaceuticals™ of Cambridge, Massachusetts, a biopharmaceutical company developing and commercializing novel therapeutic drugs like resveratrol, which are likely to be more powerful than natural forms of resveratrol.


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