Life-span extension by CR mediated by more than SIR2

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http://www.sciencemag.org/cgi/content/abstract/309/5742/1861?etoc

HST2 Mediates SIR2-Independent Life-Span Extension by Calorie

Restriction

Dudley W. Lamming,1* Magda Latorre-Esteves,1* Oliver Medvedik,1*

N. Wong,2* Felicia A. Tsang,2 Chen Wang,2 Su-Ju Lin,2{dagger} 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.