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Originally published in Science Express on 28 July 2005
Science 16 September 2005:
Vol. 309. no. 5742, pp. 1861 - 1864
DOI: 10.1126/science.1113611
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Reports

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

Dudley W. Lamming,1* Magda Latorre-Esteves,1* Oliver Medvedik,1* Stacy N. Wong,2* Felicia A. Tsang,2 Chen Wang,2 Su-Ju Lin,2{dagger} David A. Sinclair1{dagger}

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.

1 Paul F. Glenn Laboratories for the Biological Mechanisms of Aging, Department of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
2 Center for Genetics and Development, and Section of Microbiology, University of California Davis, 351 Briggs Hall, Davis, CA 95616, USA.

Published online 28 July 2005

Include this information when citing this paper.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: slin{at}ucdavis.edu (S.-J.L.), david_sinclair{at}hms.harvard.edu (D.A.S.)

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