|Dr. Jay H. Chung
Right now, there are
two ways to slow the
aging process: eat less
and exercise more.
NHLBI’s Dr. Jay H.
Chung may have identified
a third way. His
studies indicate how
resveratrol, a naturally
found in red wine, may
slow aging by mimicking
the effects of calorie
A senior investigator in the Laboratory of
Obesity and Aging Research, NHLBI, Chung
reviewed progress made in understanding how
certain compounds may mimic the effects of
calorie restriction in a recent lecture held in Lipsett
He described obesity as partly a “disease of
aging.” As people grow older, the body’s ability
to metabolize energy declines. This contributes
to weight gain, particularly around the midsection.
People with this type of fat, known as
visceral fat, are at increased risk for type 2 diabetes,
Alzheimer’s disease and heart disease,
Twenty-one years ago, scientists surmised that
resveratrol was responsible for red wine’s health
benefits. It was thought that resveratrol activated
sirtuin 1, a protein thought to protect against
aging by repairing damaged DNA and to switch
off certain genes. With age, SIRT1 levels decline.
Chung’s research indicated otherwise. He found
that resveratrol inhibited phosphodiesterases
(PDEs), enzymes that regulate cell energy use,
and that resveratrol activated SIRT1 indirectly
as a result of inhibiting PDEs.
Out of 11 PDEs, Chung focused on PDE4
because it is the dominant PDE in skeletal
muscle, the main site of glucose metabolism.
To confirm whether the metabolic benefits of
resveratrol were mediated by inhibiting PDEs,
Chung’s team gave mice rolipram, a PDE4 inhibitor.
This led to an increase in levels of cyclic
AMP, which normally rise when blood glucose
levels are low such as in fasting. Essentially,
inhibiting PDE4 mimicked the effects of a lowcalorie
diet and increased the activity of SIRT1
in skeletal muscle.
Despite the promising results, Chung cautioned that a person would have to drink 667 bottles of wine to produce resveratrol’s benefits. Besides the compound’s low potency, resveratrol could affect many other biological pathways in the body. Some of these interactions could be detrimental.
Chung is initiating a clinical trial at the Clinical Center to evaluate the glucoselowering mechanism of roflumilast, the PDE4 inhibitor that is FDA-approved for another indication, in obese, pre-diabetic individuals.