Sci. Aging Knowl. Environ., 3 August 2005
Vol. 2005, Issue 31, p. or11


HST2 Mediates SIR2-Independent Life-Span Extension by Calorie Restriction

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

Abstract: Science 28 July 2005 (10.1126/science.1113611) (Science Express Reports)

Calorie restriction (CR) extends the life span of numerous species, from yeast to rodents. Yeast Sir2 is an 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 rDNA, 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.


Science of Aging Knowledge Environment. ISSN 1539-6150