Public release date: 3-Jun-2008
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Contact: Tomas Prolla
taprolla@wisc.edu
608-265-5204
University of Wisconsin-Madison
Agent in red wine found to keep hearts young

MADISON - How, scientists wonder, do the French get away with a clean
bill of heart health despite a diet loaded with saturated fats?

The answer to the so-called "French paradox" may be found in red wine.
More specifically, it may reside in small doses of resveratrol, a
natural constituent of grapes, pomegranates, red wine and other foods,
according to a new study by an international team of researchers.

Writing this week (June 3) in the online, open-access journal Public
Library of Science One, the researchers report that low doses of
resveratrol in the diet of middle-aged mice has a widespread influence
on the genetic levers of aging and may confer special protection on
the heart.

Specifically, the researchers found that low doses of resveratrol
mimic the effects of what is known as caloric restriction - diets with
20-30 percent fewer calories than a typical diet - that in numerous
studies has been shown to extend lifespan and blunt the effects of
aging.

"This brings down the dose of resveratrol toward the consumption
reality mode," says senior author Richard Weindruch, a University of
Wisconsin-Madison professor of medicine and a researcher at the
William S. Middleton Memorial Veterans Hospital. "At the same time, it
plugs into the biology of caloric restriction."

Previous research has shown that resveratrol in high doses extends
lifespan in invertebrates and prevents early mortality in mice given a
high-fat diet. The new study, conducted by researchers from academia
and industry, extends those findings, showing that resveratrol in low
doses and beginning in middle age can elicit many of the same benefits
as a reduced-calorie diet.

"Resveratrol is active in much lower doses than previously thought and
mimics a significant fraction of the profile of caloric restriction at
the gene expression level," says Tomas Prolla, a UW-Madison professor
of genetics and a senior author of the new report.

The group explored the influence of the agent on heart, muscle and
brain by looking for changes in gene expression in those tissues. As
animals age, gene expression in the different tissues of the body
changes as genes are switched on and off.

In the new study - which compared the genetic crosstalk of animals on
a restricted diet with those fed small doses of resveratrol - the
similarities were remarkable, explains lead author Jamie Barger of
Madison-based LifeGen Technologies. In the heart, for example, there
are at least 1,029 genes whose functions change with age, and the
organ's function is known to diminish with age. In animals on a
restricted diet, 90 percent of those heart genes experienced altered
gene expression profiles, while low doses of resveratrol thwarted age-
related change in 92 percent. The new findings, say the study's
authors, were associated with prevention of the decline in heart
function associated with aging.

In short, a glass of wine or food or supplements that contain even
small doses of resveratrol are likely to represent "a robust
intervention in the retardation of cardiac aging," the authors note.

That finding may also explain the remarkable heart health of people
who live in some regions of France where diets are soaked in saturated
fats but the incidence of heart disease, a major cause of mortality in
the United States, is low. In France, meals are traditionally
complemented with a glass of red wine.

The new resveratrol study is also important because it suggests that
caloric restriction, which has been widely studied in animals from
spiders to humans, and resveratrol may govern the same master genetic
pathways related to aging.

"There must be a few master biochemical pathways activated in response
to caloric restriction, which in turn activate many other pathways,"
explains Prolla. "And resveratrol seems to activate some of these
master pathways as well."

The new findings, according to Weindruch and Prolla, provide strong
evidence that resveratrol can improve quality of life through its
influence on the different parameters of aging such as cardiac
function. However, whether the agent can extend lifespan in ways
similar to caloric restriction will require further study, according
to the new report's authors.

###

The work of the Wisconsin team was funded by grants from the National
Institutes of Health and DSM Nutritional Products of Basel,
Switzerland.

- Terry Devitt, (608) 262-8282, trdevitt@wisc.edu

CONTACT: Tomas Prolla, (608) 265-5204, (608) 556-0175 (cell),
taprolla@wisc.edu; Richard Weindruch (608) 256-1901 ext. 11642, (608)
556-0176 (cell), rhweindr@wisc.edu

It also contains tannins and polycyclic pigments with  anti-amyloid
properties.