Regulation of aging and age-related disease by DAF-16 and heat-shock factor.

Authors: Hsu AL; Murphy CT; Kenyon C

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.

Keywords: Aging/genetics/*physiology; Animals; Caenorhabditis elegans/genetics/*physiology; Caenorhabditis elegans Proteins/genetics/*physiology; Gene Expression Regulation; Heat-Shock Response/genetics/physiology; Insulin/genetics/physiology; Longevity/genetics/physiology; Mutation; Receptor, IGF Type 1/genetics/physiology; Receptor, Insulin/genetics/physiology; Transcription Factors/*physiology
Journal: Science (New York, N.Y.)
Volume: 300
Issue: 5622
Pages: 1142-5
Date: May 17, 2003
PMID: 12750521
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Citation:

Hsu AL, Murphy CT, Kenyon C (2003) Regulation of aging and age-related disease by DAF-16 and heat-shock factor. Science (New York, N.Y.) 300: 1142-5.


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