Red Wine Delivering

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.