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. 2004 Jul 16;305(5682):390-2.
doi: 10.1126/science.1099196. Epub 2004 Jun 17.

Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase

Haim Y Cohen  1 , Christine Miller, Kevin J Bitterman, Nathan R Wall, Brian Hekking, Benedikt Kessler, Konrad T Howitz, Myriam Gorospe, Rafael de Cabo, David A Sinclair
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Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase

Haim Y Cohen et al. Science. .

Abstract

A major cause of aging is thought to result from the cumulative effects of cell loss over time. In yeast, caloric restriction (CR) delays aging by activating the Sir2 deacetylase. Here we show that expression of mammalian Sir2 (SIRT1) is induced in CR rats as well as in human cells that are treated with serum from these animals. Insulin and insulin-like growth factor 1 (IGF-1) attenuated this response. SIRT1 deacetylates the DNA repair factor Ku70, causing it to sequester the proapoptotic factor Bax away from mitochondria, thereby inhibiting stress-induced apoptotic cell death. Thus, CR could extend life-span by inducing SIRT1 expression and promoting the long-term survival of irreplaceable cells.

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