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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.

Original publication

DOI

10.1126/science.1099196

Type

Journal article

Journal

Science

Publication Date

16/07/2004

Volume

305

Pages

390 - 392

Keywords

Acetylation, Adipose Tissue, Alleles, Animals, Antigens, Nuclear, Apoptosis, Caloric Restriction, Cell Line, Cell Survival, DNA-Binding Proteins, Histone Deacetylases, Humans, Insulin, Insulin-Like Growth Factor I, Kidney, Ku Autoantigen, Liver, Male, Mitochondria, Mutation, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-bcl-2, RNA, Small Interfering, Rats, Rats, Inbred F344, Sirtuin 1, Sirtuins, bcl-2-Associated X Protein