HST2 mediates SIR2-independent life-span extension by calorie restriction.

Authors: Lamming, Dudley W; Latorre-Esteves, Magda; Medvedik, Oliver; Wong, Stacy N; Tsang, Felicia A; Wang, Chen; Lin, Su-Ju; Sinclair, David A

Abstract: Calorie restriction (CR) extends the life span of numerous species, from yeast to rodents. Yeast Sir2 is a nicotinamide adenine dinucleotide (NAD+-dependent histone deacetylase that has been proposed to mediate the effects of CR. However, this hypothesis has been challenged by the observation that CR can extend yeast life span in the absence of Sir2. Here, we show that Sir2-independent life-span extension is mediated by Hst2, a Sir2 homolog that promotes the stability of repetitive ribosomal DNA, the same mechanism by which Sir2 extends life span. These findings demonstrate that the maintenance of DNA stability is critical for yeast life-span extension by CR and suggest that, in higher organisms, multiple members of the Sir2 family may regulate life span in response to diet.

Keywords: *Caloric Restriction; DNA, Fungal/genetics; DNA, Ribosomal/genetics; Gene Deletion; Gene Silencing; Genes, Fungal; Histone Deacetylases/genetics/physiology; *Longevity; Mutation; Niacinamide/pharmacology; Recombination, Genetic; Saccharomyces cerevisiae/genetics/*physiology; Saccharomyces cerevisiae Proteins/*genetics/*physiology; Silent Information Regulator Proteins, Saccharomyces cerevisiae/physiology; Sirtuin 2; Sirtuins/*genetics/*physiology
Journal: Science
Volume: 309
Issue: 5742
Pages: 1861-4
Date: July 30, 2005
PMID: 16051752
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Lamming, Dudley W, Latorre-Esteves, Magda, Medvedik, Oliver, Wong, Stacy N, Tsang, Felicia A, Wang, Chen, Lin, Su-Ju, Sinclair, David A (2005) HST2 mediates SIR2-independent life-span extension by calorie restriction. Science 309: 1861-4.

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