Research Links Caloric Restriction to “Anti-Aging Molecule”

February 19, 2010

Posted by Carey Rossi

Researchers at Mount Sinai School of Medicine set out to address a question that has been challenging scientists for years: How do dietary restriction—and the reverse, over consumption—produce protective effects against aging and disease?

A possible answer lies in a two-part study published in the November 17, 2009, edition of the journal Public Library of Science Biology. It examines how caloric restriction and a high-caloric diet influence biochemical responses.

The researchers pieced together a molecular puzzle that revealed lower-calorie diets slow the development of some age-related conditions such as Alzheimer’s disease, as well as the aging process. And here is the interesting thing: it doesn’t seem to matter whether fats, proteins, or carbohydrates are cut.

“It may not be about counting calories or cutting out specific nutrients,” said lead researcher Charles Mobbs, PhD, professor of neuroscience and of geriatrics and palliative medicine at Mount Sinai School of Medicine, in a prepared statement, “but how a reduction in dietary intake impacts the glucose metabolism, which contributes to oxidative stress.” Meanwhile, a high calorie diet may accelerate age-related disease by promoting oxidative stress.

How does this work? Dietary restriction induces a transcription factor called CREB-binding protein (CBP), a protein molecule which controls the activity of genes that regulate cellular function. “We discovered that CBP predicts lifespan and accounts for 80% of lifespan variation in mammals,” said Mobbs, who lead both animal studies. The first examined roundworms that were genetically altered to develop Alzheimer’s disease-like symptoms. After decreasing the mammals’ dietary intake, researchers found that when dietary restriction was maintained throughout the worms’ adulthood, lifespan increased by 65% and the Alzheimer’s disease-related paralysis decreased by about 50%. In addition, they showed that dietary restriction activates CBP. The second study examined the other end of the dietary spectrum—overeating. By looking at mice, Mobbs and his colleagues found that diabetes reduces activation of CBP, leading him to conclude that a high-calorie diet that leads to diabetes would have the opposite effect of dietary restriction and would accelerate aging.

All of this has led to Mobbs hypothesizing that dietary restriction induces CBP by blocking glucose metabolism, which produces oxidative stress—a cellular process that leads to tissue damage and also promotes cancer cell growth. But here is the real ah-ha: reducing the amount of calories taken in triggers CBP for as long as the restriction is maintained and CBP responds to changes in glucose within hours, indicating genetic communications respond quickly to fluctuations in dietary intake. This means gobbling down a meal that is worth a day’s total calorie intake on a whim could have damaging effects.

The Anti-Aging Bottom Line: While this research will probably be used to develop drugs that mimic the protective effects of CBP, you can reap the benefits of this research by being calorie wise. Researchers found that slashing your calories by just 10% can help increase lifespan. While the magic number could be a 30% decrease in the amount of calories consumed—researchers found that it increased lifespan over 50% while slowing the development of age-related diseases—dipping below 1,200 calories could starve your body, which in turn would lead to a shorter lifespan.