Abstract
When overexpressed, the NAD-dependent protein deacetylase Sir2 extends the lifespan of both budding yeast and the nematode worm Caenorhabditis elegans. In the worm, this extension of lifespan requires the FOXO transcription factor daf-16. Three recent articles focusing on mammalian homologues of Sir2 and FOXO have highlighted the mechanisms that generate this genetic interaction. Mammalian SIRT1 deacetylates FOXO3 and/or FOXO4, thus attenuating FOXO-induced apoptosis and potentiating FOXO-induced cell-cycle arrest. SIRT1 might increase longevity by shifting FOXO dependent responses away from cell death and towards cell survival.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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Cell Cycle Proteins
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Cell Survival / physiology
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Drosophila Proteins / genetics
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Drosophila Proteins / metabolism*
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Forkhead Box Protein O3
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Forkhead Transcription Factors
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Histone Deacetylases / genetics
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Histone Deacetylases / metabolism*
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Humans
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Sirtuin 1
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Sirtuins / genetics
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Sirtuins / metabolism*
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Transcription Factors / genetics
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Transcription Factors / metabolism*
Substances
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Cell Cycle Proteins
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Drosophila Proteins
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FOXO protein, Drosophila
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FOXO4 protein, human
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Forkhead Box Protein O3
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Forkhead Transcription Factors
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FoxO3 protein, mouse
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Transcription Factors
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SIRT1 protein, human
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Sirtuin 1
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Sirtuins
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Histone Deacetylases