Editors' ChoiceAging

Longevity Genes in Yeast and Worm

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Science's STKE  13 Mar 2001:
Vol. 2001, Issue 73, pp. tw1
DOI: 10.1126/stke.2001.73.tw1

Extra copies of the SIR2 gene in yeast increase the number of times a mother yeast can reproduce by budding. This is the operational definition of aging in yeast (see article by Gems). Overexpression of the worm gene with the most similarity to yeast SIR2 called sir-2.1 also increased life-span in the worm Caenorhabditis elegans. The increased life-span required a functional forkhead transcription factor, DAF-16, whose activity is inhibited by the insulin-like pathway in the worm. Mutations in the insulin-like signaling pathway also affect worm life-span by a mechanism requiring DAF-16. Sir-2.1 appears to be a regulator of the insulin-like pathway based on several criteria, including synergism with the genetic mutants of the TGF-β pathway and a lack of synergism with mutants of the insulin-like receptor gene daf-2. In yeast, SIR2 alters chromatin structure, resulting in gene silencing. Tissenbaum and Guarente suggest that Sir-2.1 may repress the expression of factors involved in activating the insulin-like pathway, promoting the activity of DAF-16 and prolonging life-span.

D. Gems, Yeast longevity gene goes public. Nature 410, 154-155 (2001). [Online Journal]

H. A. Tissenbaum, L. Guarente, Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans. Nature 410, 227-230 (2001). [Online Journal]

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