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Published Online July 28, 2005
Science DOI: 10.1126/science.1113611

Reports

Submitted on April 15, 2005
Accepted on July 8, 2005

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*, David A. Sinclair 1*

1 Paul F. Glenn Laboratories, 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.

* To whom correspondence should be addressed.
Su-Ju Lin , E-mail: slin{at}ucdavis.edu
David A. Sinclair , E-mail: david_sinclair{at}hms.harvard.edu

Calorie restriction (CR) extends the lifespan 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 lifespan in the absence of Sir2. Here we show Sir2-independent lifespan extension is mediated by Hst2, a Sir2 homolog that promotes the stability of repetitive rDNA, the same mechanism by which Sir2 extends lifespan. These findings demonstrate that the maintenance of DNA stability is critical for yeast lifespan extension by CR and suggest that, in higher organisms, multiple members of the Sir2 family may regulate lifespan in response to diet.


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