Resveratrol Extending LifespanThe recently introduced integrative guided-inquiry experiment explains various fundamental chemical concepts related to different biologically relevant molecules like resveratrol. The results of the photoisomerization of the molecule show that it is a very effective chemopreventative agent that can extend the lifespan in several organisms. Resveratrol Found to Improve Health, But Not Longevity in Aging Mice StudyScientists have found that the compound resveratrol slows age-related deterioration and functional decline of mice on a standard diet, but does not increase longevity when started at middle age. This study, conducted and supported in part by the National Institute on Aging (NIA), part of the National Institutes of Health, is a follow-up to 2006 findings that resveratrol improves health and longevity of overweight, aged mice. The report confirms previous results suggesting the compound, found naturally in foods like grapes and nuts, may mimic, in mice, some of the effects of dietary or calorie restriction, the most effective and reproducible way found to date to alleviate age-associated disease in mammals. The findings, published July 3, 2008, in Cell Metabolism, may increase interest in resveratrol as a possible intervention for age-related declines, said NIA scientists. The authors emphasized, however, that their findings are based on research in mice, not in humans, and have no immediate and direct application to people, whose health is influenced by a variety of factors beyond those which may be represented in the animal models. The study is a collaborative effort between the laboratories of Rafael de Cabo, Ph.D., of the Laboratory of Experimental Gerontology at the NIA; David A. Sinclair, Ph.D., of the Glenn Laboratories for Molecular Biology of Aging at Harvard Medical School; and an international group of researchers. The investigators compared mice fed a standard diet, a high-calorie diet, or an every-other-day feeding regimen with or without high- or low-dose resveratrol to study the impact of resveratrol on aging and health. In previous studies, different forms of dietary restriction, including every-other-day feeding, have been shown to improve markers of health. “Research is attempting to understand the process of aging and to determine how interventions can influence this process. Dietary restriction has well-documented health benefits in mammals, and the study of possible mimetics of it, such as resveratrol, are of great interest,” said NIA Director Richard J. Hodes, M.D. “Resveratrol has produced significant effects in animal models, now including mice, where it mimics some, but not all, consequences of caloric restriction. Its effects in humans remain to be studied.” A major finding of the study reported today is that resveratrol prevented age-related and obesity-related cardiovascular functional decline in the mice as determined by several parameters. Total cholesterol was significantly reduced in 22-month-old non-obese mice after 10 months of resveratrol treatment, although triglyceride levels had only a slight, non-significant trend toward a decrease. Further, the aortas of 18-month-old obese and non-obese mice treated with resveratrol functioned significantly better than untreated mice. Resveratrol also moderated inflammation in the heart. Resveratrol Red Wine and Cancer PreventionResearch on the antioxidants found in red wine has shown that they may help inhibit the development of certain cancers. Resveratrol has been shown to reduce tumor incidence in animals by affecting one or more stages of cancer development. It has been shown to inhibit growth of many types of cancer cells in culture. Recent evidence from animal studies suggests this anti-inflammatory compound may be an effective chemopreventive agent in three stages of the cancer process: initiation, promotion and progression. Red wine is a rich source of biologically active phytochemicals, chemicals found in plants. Particular compounds called polyphenols found in red wine-such as catechins and resveratrol-are thought to have anti oxidant or anti cancer properties. 1. What are polyphenols and how do they prevent cancer? Polyphenols are antioxidant compounds found in the skin and seeds of grapes. When wine is made from these grapes, the alcohol produced by the fermentation process dissolves the polyphenols contained in the skin and seeds. Red wine contains more polyphenols than white wine because the making of white wine requires the removal of the skins after the grapes are crushed. The phenols in red wine include catechin, gallic acid and epicatechin. Polyphenols have been found to have antioxidant properties. Antioxidants are substances that protect cells from oxidative damage caused by molecules called free radicals. These chemicals can damage important parts of cells, including proteins, membranes and DNA. Cellular damage caused by free radicals has been implicated in the development of cancer. Research on the antioxidants found in red wine has shown that they may help inhibit the development of certain cancers. Resveratrol is a type of polyphenol called a phytoalexin, a class of compounds produced as part of a plant’s defense system against disease. It is produced in the plant in response to an invading fungus, stress, injury, infection or ultraviolet irradiation. Red wine contains high levels of resveratrol, as do grapes, raspberries, peanuts and other plants. Resveratrol has been shown to reduce tumor incidence in animals by affecting one or more stages of cancer development. It has been shown to inhibit growth of many types of cancer cells in culture. Evidence also exists that it can reduce inflammation. It also reduces activation of NF kappa B, a protein produced by the body’s immune system when it is under attack. This protein affects cancer cell growth and metastasis. Resveratrol is also an antioxidant. 3. What have red wine studies found? The cell and animal studies of red wine have examined effects in several cancers including leukemia, skin, breast and prostate cancers. Scientists are studying resveratrol to learn more about its cancer preventive activities. Recent evidence from animal studies suggests this anti-inflammatory compound may be an effective chemopreventive agent in three stages of the cancer process: initiation, promotion and progression. Research studies published in the International Journal of Cancer show that drinking a glass of red wine a day may cut a man’s risk of prostate cancer in half and that the protective effect appears to be strongest against the most aggressive forms of the disease. It was also seen that men who consumed four or more 4-ounce glasses of red wine per week have a 60 percent lower incidence of the more aggressive types of prostate cancer. However, studies of the association between red wine consumption and cancer in humans are in their initial stages. Although consumption of large amounts of alcoholic beverages may increase the risk of some cancers, there is growing evidence that the health benefits of red wine are related to its nonalcoholic components. Resveratrol Biotransformation EnzymesSome compounds are not carcinogenic until they have been metabolized in the body by cytochrome P450 enzymes. By inhibiting the expression and activity of certain cytochrome P450 enzymes, resveratrol could help prevent cancer by decreasing exposure to these activated carcinogens. In contrast, increasing the activity of phase II biotransformation enzymes generally promotes the excretion of potentially toxic or carcinogenic chemicals. Resveratrol has been found to increase the expression and activity of the phase II enzyme NAD(P)H:quinone reductase in cultured cells. Resveratrol Metabolism and BioavailabilityAlthough trans-resveratrol appears to be well-absorbed by humans when taken orally, its bioavailability is relatively low due to its rapid metabolism and elimination. Resveratrol metabolites are primarily detected upon oral exposure to trans-resveratrol. When six healthy men and women took an oral dose of 25 mg of trans-resveratrol, only traces of the unchanged resveratrol were detected in plasma (blood). Plasma concentrations of resveratrol and metabolites peaked around 60 minutes later at concentrations around 2 micromoles/liter (491 micrograms/liter). A study in 12 healthy men administered an oral dose of 25 mg of trans-resveratrol per 70 kg of body weight reported that serum concentration of resveratrol and metabolites peaked at 30 minutes after administration. The concentration of total resveratrol (resveratrol and metabolites) ranged from 416 to 471 micrograms/liter, depending on whether resveratrol was administered in wine, vegetable juice, or grape juice. Results of another study suggested that the bioavailability of resveratrol from grape juice, which contains mostly glucosides of resveratrol (piceid), may be even lower than that of trans-resveratrol. A recent study reported that bioavailability of trans-resveratrol from red wine did not differ when the wine was consumed with a meal (low- or high-fat) versus on an empty stomach. What is Resveratrol?Resveratrol is a phytoalexin produced naturally by several plants when under attack by pathogens such as bacteria or fungi. Resveratrol has also been produced by chemical synthesis and is sold as a nutritional supplement derived primarily from Japanese knotweed. In mouse and rat experiments, anti-cancer, anti-inflammatory, blood-sugar-lowering and other beneficial cardiovascular effects of resveratrol have been reported. |
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