Enzyme Responsible for the Benefits of Caloric Restriction Identified

Researchers are beginning to define the molecular basis for the improvement in health and increase in life expectancy induced by reducing caloric intake and maintaining a reduced calorie diet.

Investigators at University College London (United Kingdom) genetically engineered a line of "knockdown" mice that lacked the gene for the enzyme ribosomal S6 Kinase 1 (S6K1). S6K1 is a component of the nutrient-responsive mTOR (mammalian target of rapamycin) signaling pathway, which guides the organism's response to changing levels of nutrients.

Results comparing normal and S6K1 knockdown mice were published in the October 2, 2009, issue of the journal Science. They showed that at an age of 600 days (the mouse equivalent of middle age) female knockout mice were leaner, and had stronger bones than did the normal females. The female knockdown mice did not show the usual age-related decline in insulin sensitivity. They performed better at motor performance tasks and were more inquisitive and exploratory. On average, the female knockout mice lived for 950 days, over 160 days longer than the control group. While the male knockout mice demonstrated the same overall better health characteristics, they did not experience the extended lifespan.

"Blocking the action of the S6K1 protein helps prevent a number of age-related conditions in female mice," explained senior author Dr. Dominic Withers, professor of diabetes and endocrinology research at University College London. "The mice lived longer and were leaner, more active and generally healthier than the control group. We added "life to their years" as well as "years to their lives"."

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