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05.2005

Massachusetts Beverage Business

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Article By: Harvey Finkel, MD

Recent research has demonstrated that some of the polyphenols of wine appear to extend life span by mechanisms new to us. Maybe Ponce de Leon should have sought the fountain of youth in the vineyards of his native Spain instead of sloshing through the swamps of Florida.

Be aware that, thus far, these happy tidings pertain only to lower orders of beings - yeast, roundworm, fruitfly. The initial work (Howitz KT, et al: Nature 2003; 425: 191-196 (11 Sep)) from a team led by David A. Sinclair at the Harvard Medical School, Boston, and BIOMOL Research Laboratories, Inc., Plymouth Meeting, PA, was stimulated by the observation that the stress of severe calorie restriction (30 to 40 percent fewer than normal) slows the pace of aging and increases the maximum life span of various species. The defense response against such environmental stress involves regulatory genes of longevity that, activated by the stress, have evolved to promote survival. These genes function by increasing the activity of the sirtuin enzyme group, especially Sir2, which, in turn, stabilizes DNA and prevents lethal accumulation of toxic products in older cells.

Obviously, promotion of a stressful degree of caloric reduction is impractical, despite all the attention devoted to overeating by the health professions and the news media. Substances that mimic calorie restriction by stimulating sirtuins and increasing life span were sought, and our old friends, the antioxidant polyphenols of grape skins and wine, answered the call. These compounds perform a complex of functions in vines, including protecting from fungus and sunburn; in wine, preservation from premature senility and infection and enhancement of color and flavor; and, we believe, in man, probably mediated, in part, by inhibition of oxidation and stimulation of sirtuins. Their production in plants is stimulated by such stresses as dehydration, lack of nourishment, ultraviolet radiation, and infection. In man, the polyphenols appear to alleviate the disabling and life-shortening degenerative disorders atherosclerosis, dementia, and cancer, benefits also noted in calorie-restricted rodents.

Seventeen polyphenols were found active, especially the now-familiar resveratrol, which extended yeast life span by 70 percent, and which was studied in more detail. Fisetin and butein gave 55 and 31 percent longer life, respectively. Modest concentrations of resveratrol were effective, but higher concentrations not more so, perhaps even less so - a puzzle. Treating young cells, then stopping, had no lasting benefit.

Further research more recently has demonstrated that polyphenols can induce increases in life span of up to 14 percent in worms, 29 percent in flies, most impressively accompanied by increased fertility and maintenance of vigor. It appears that aging and senescence are delayed. Recent research also indicate that mammalian (mouse) cells are subject to the same stimuli. Early studies have suggested that resveratrol activates sirtuins in human cells too. An additional study of mice has revealed that a closely related regulatory gene, Sirt1, also activated by resveratrol, reduces fat accumulation and favorably alters fat metabolism, thereby alleviating diabetes, atherosclerosis, and aging - and extending life.

Aging is in part due to oxidative stress, but the lengthening of life at the hands of the antioxidant polyphenols is likely more a function of stimulation of the sirtuins. Part of the benefits may come from suppression of a cancer-causing gene, part from delaying programmed cell suicide, giving the cells additional time to repair damage, thus preventing unnecessary cell death.

Clearly, more work and time are needed, but isn't all this intriguing? Resveratrol is absorbed by, but is excreted very rapidly from, the human body, so it is uncertain whether effective levels can be achieved. There is talk of marketing resveratrol capsules, but don't forget red wine, our main source of these polyphenols, whose alcohol abundantly enhances the health benefits of moderate drinking, and whose total package is unbeatable.

And for those of us of more than average weight, calorie restriction might confer health benefits in addition to those of wine.

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