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Science 16 May 2003:
Vol. 300. no. 5622, pp. 1142 - 1145
DOI: 10.1126/science.1083701
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Reports

Regulation of Aging and Age-Related Disease by DAF-16 and Heat-Shock Factor

Ao-Lin Hsu, Coleen T. Murphy, Cynthia Kenyon*

The Caenorhabditis elegans transcription factor HSF-1, which regulates the heat-shock response, also influences aging. Reducing hsf-1 activity accelerates tissue aging and shortens life-span, and we show that hsf-1 overexpression extends lifespan. We find that HSF-1, like the transcription factor DAF-16, is required for daf-2–insulin/IGF-1 receptor mutations to extend life-span. Our findings suggest this is because HSF-1 and DAF-16 together activate expression of specific genes, including genes encoding small heat-shock proteins, which in turn promote longevity. The small heat-shock proteins also delay the onset of polyglutamine-expansion protein aggregation, suggesting that these proteins couple the normal aging process to this type of age-related disease.

Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143–2200, USA.

* To whom correspondence should be addressed. E-mail: ckenyon{at}biochem.ucsf.edu

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