Researchers have moved a step forward in understanding how calorie restriction is linked to lifespan extension in mammals. In this week's issue of Nature, a group from the United States reports that SIRT1—the mammalian version of a protein linked to longevity in simpler organisms—controls glucose metabolism in mice in response to fasting.

Pere Puigserver of Johns Hopkins University and colleagues found that fasting signals induce the SIRT1 protein in the liver. This protein is one of the mammalian homologues of Sir2, known to extend lifespan in yeast and worms. SIRT1 then interacts with the coactivator PGC-1alpha, which, in turn, triggers glucose production, a key metabolic change associated with extended lifespan.

"Our work provides a novel connection between PGC-1alpha, a protein involved in the food-deprivation response, and SIRT1, a protein linked to aging in lower organisms," Puigserver told The Scientist.

SIRT1, which is an NAD+-dependent...

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