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Science 300 (5622): 1142-1145

Copyright © 2003 by the American Association for the Advancement of Science

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

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

Abstract: 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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S. T. Henderson, M. Bonafe, and T. E. Johnson (2006)
J Gerontol A Biol Sci Med Sci 61, 444-460
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De Novo Appearance and "Strain" Formation of Yeast Prion [PSI+] Are Regulated by the Heat-Shock Transcription Factor.
K.-W. Park, J.-S. Hahn, Q. Fan, D. J. Thiele, and L. Li (2006)
Genetics 173, 35-47
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