Athletes and non-athletes alike may want
to raise a glass to resveratrol, an ingredient
in grapes that researchers say doubled
the physical endurance of mice in a new
study, while protecting them against diabetes
and obesity.
Mice given high
doses of the compound were able to run
twice as far on treadmills than they normally
could, French researchers reported.
Resveratrol might even help the rodents
live longer, they say.
"The compound resveratrol, found
in the skin of red grapes and cranberries,
was known to activate SIRT1, an enzyme
known to be involved in lifespan extension,"
explained lead researcher Dr. Johan Auwerx,
from the Institute of Genetics and Molecular
and Cellular Biology in Illkirch, France.
These results, published in the Nov.
16 issue of Cell, add to findings
from a recent study that showed that resveratrol
improved health and lengthened survival
of mice placed on a high-calorie diet.
While studies have so far been limited
to mice, the French team said they had
also found a genetic link to energy expenditure
in humans that looks like it might be
similarly affected by resveratrol.
"Our study shows that activation
of SIRT1 by resveratrol is a very promising
and well-tolerated approach to treat common
metabolic diseases, such as obesity and
type 2 diabetes," Auwerx said.
The study involved obese mice with a
condition that mimicked type 2 diabetes.
Auwerx's team found that resveratrol
activated the SIRT1 gene, inducing the
activity of mitochondria, the tiny energy
factories within cells. By activating
mitochondria, resveratrol causes the cells
to burn more energy than they normally
could.
Burning more energy protects against
fat accumulation and type 2 diabetes,
the research team explained. Increasing
mitochondria activity also improves the
performance of certain tissues, most especially
skeletal muscles.
"That is why we saw a spectacular
increase in endurance in the mice, which
doubled the distance they run," Auwerx
explained.
"We showed this not only in cultured
cells and mice, but also, more importantly,
the first time in humans, where we linked
the SIRT1 gene with energy expenditure,"
Auwerx said.
Resveratrol or its analogs could prove
useful in treating several diseases that
are characterized by abnormal mitochondrial
activity, Auwerx said. "In the first
case, you can think about applications
in the treatment of obesity and type 2
diabetes," he said. "Many more
diseases could benefit from increased
mitochondrial activity, most notably neurodegenerative
disorders, such as Parkinson's disease
and Huntington's," he added.
This study was paid for by Sirtris Pharmaceuticals,
which developed the compound used in the
experiments.
But if you think that drinking more wine
or taking resveratrol supplements might
turn you into a super-athlete, think again,
said Sirtris CEO Dr. Christoph Westphal.
"Native resveratrol from red wine
or nutraceuticals cannot reach therapeutic
levels in man," he said. "You
would need to drink hundreds of glasses
of red wine or take hundreds of nutraceutical
pills in a day to get a therapeutic dose."
According to Westphal, the company has
completed two phase 1 studies with 85
human volunteers of an improved formulation
of resveratrol which reaches therapeutic
levels in man and is safe.
In addition, Sirtris has started giving
diabetic patients its resveratrol compound
in a 28-day phase 1 trial to test the
safety of the drug and to see how it affects
glucose levels.
"We are also initiating a phase
1 study in a rare, very severe mitochondrial
disorder called MELAS," Westphal
said. The condition -- "mitochondrial
myopathy, encephalopathy, lactacidosis,
stroke" (MELAS) -- is a progressive
neurodegenerative disorder.
One expert was cautious about the findings.
"This is an important addition
to the body of work that is showing that
you can activate anti-aging genetic pathways,"
said David Sinclair, an associate professor
of pathology at Harvard Medical School,
and a cofounder of Sirtris.
He called the study an important sep
in the development of new drugs to fight
heart disease, Alzheimer's and age-relate
other woes. "In five years, we should
know if the results obtained in mice can
be achieved in people," he said.
The compound's usefulness against diabetes
remains unproven, Sinclair said. "A
mouse is not a human," he said. "It
would be amazing if it worked in humans.
But we will have to wait and see."
Another expert expressed similar skepticism.
"It's clear that the authors of
the Cell paper want to strongly
argue that their data show a causal link
between activation of SIRT1 and the effects
of resveratrol," said Matt Kaeberlein,
an assistant professor of pathology at
the University of Washington. "While
all of their data is consistent with this
model, and the data is compelling, there
really is no causal evidence that the
effects of resveratrol in mice require
SIRT1 activation," he said.
Kaeberlein suggested that to really
test their theory, the researchers should
have experimented with mice that did not
have the SIRT1 gene, to see whether these
mice would respond to resveratrol when
fed a high-fat diet.
"Also, there is abundant evidence
that resveratrol acts on proteins other
than SIRT1, so it's premature to conclude
that everything seen in this paper is
due to effects on SIRT1," he said.