Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase

Haim Y. Cohen; Christine Miller; Kevin J. Bitterman; Nathan R. Wall; Brian Hekking; Benedikt Kessler; Konrad T. Howitz; Myriam Gorospe; Rafael De Cabo; David A. Sinclair

doi:10.1126/science.1099196

Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase

Haim Y. Cohen, Christine Miller, Kevin J. Bitterman, Nathan R. Wall, Brian Hekking, Benedikt Kessler, Konrad T. Howitz, Myriam Gorospe, Rafael De Cabo, David A. Sinclair

Research output: Contribution to journal › Article › peer-review

1748 Scopus citations

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.

Original language	English
Pages (from-to)	390-392
Number of pages	3
Journal	Science
Volume	305
Issue number	5682
DOIs	https://doi.org/10.1126/science.1099196
State	Published - 16 Jul 2004
Externally published	Yes

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title = "Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase",

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.",

author = "Cohen, {Haim Y.} and Christine Miller and Bitterman, {Kevin J.} and Wall, {Nathan R.} and Brian Hekking and Benedikt Kessler and Howitz, {Konrad T.} and Myriam Gorospe and {De Cabo}, Rafael and Sinclair, {David A.}",

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AU - Cohen, Haim Y.

AU - Miller, Christine

AU - Bitterman, Kevin J.

AU - Wall, Nathan R.

AU - Hekking, Brian

AU - Kessler, Benedikt

AU - Howitz, Konrad T.

AU - Gorospe, Myriam

AU - De Cabo, Rafael

AU - Sinclair, David A.

PY - 2004/7/16

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AB - 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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Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase

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