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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 histonedeacetylase that has been proposed to mediate the effects ofCR. However, this hypothesis has been challenged by the observationthat CR can extend yeast lifespan in the absence of Sir2. Herewe 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 findingsdemonstrate that the maintenance of DNA stability is criticalfor yeast lifespan extension by CR and suggest that, in higherorganisms, multiple members of the Sir2 family may regulatelifespan in response to diet.
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