From Our 2006 Archives

Carb-Starved Brain Fights Alzheimer's

Calorie Restriction Triggers Plaque-Busting Process in Brain

WebMD Medical News

Reviewed ByLouiseChang,MD
on Monday, June 19, 2006

June 19, 2006 -- A natural substance linked to longer lifespan fights Alzheimer's disease, mouse studies show.

The substance is SIRT1, a member of the family of enzymes called sirtuins. Virtually every living thing -- from bacteria to humans -- makes sirtuins.

It's long puzzled researchers why animals that eat barely enough calories to survive live longer than well-fed animals. The reason may be that in response to calorie restriction, sirtuins become more active.

Calorie restriction -- especially carb restriction -- also prevents brain-clogging plaque in mice bred to get Alzheimer's disease. That's because their SIRT1 activity goes up, finds a research team including Giulio M. Pasinetti, MD, PhD, of New York's Mount Sinai School of Medicine, and colleagues.

"These results demonstrate for the first time a role for SIRT1 activation in the brain as a novel mechanism through which calorie restriction may influence Alzheimer's disease," the researchers conclude. "The study provides a potentially novel pharmacological strategy for Alzheimer's disease prevention and/or treatment."

The findings appear in the July 2006 issue of the Journal of Biological Chemistry.

Pasinetti's team put Alzheimer's-disease-prone mice on a low-cal diet that cut their calories by 70%. Analysis of their brain cells showed they had less plaque-building activity -- and higher levels of SIRT1 -- than mice allowed to eat as much as they pleased.

The SIRT1, they found, increased a plaque-preventing process in the brain. When the researchers put the gene for human SIRT1 into the brains of these mice -- or when they gave the mice a SIRT1-activating chemical -- they saw higher levels of this plaque-clearing activity.

Pasinetti and colleagues suggest that these findings point to an exciting target for new drugs that can treat and prevent Alzheimer's disease.

SOURCES: Qin, W. Journal of Biological Chemistry, July 2006; published online ahead of print June 2, 2006. News release, Mount Sinai School of Medicine.

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