Regulation of aging and age-related disease by DAF-16 and heat-shock factor.
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.
Hsu
Ao-Lin
AL
Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143-2200, USA.
Murphy
Coleen T
CT
Kenyon
Cynthia
C
D000375:Aging / Q000235:genetics / Q000502:physiology*; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D051858:Forkhead Transcription Factors; D005786:Gene Expression Regulation; D018869:Heat-Shock Response / Q000235:genetics / Q000502:physiology; D007328:Insulin / Q000235:genetics / Q000502:physiology; D008136:Longevity / Q000235:genetics / Q000502:physiology; D009154:Mutation; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000502:physiology; D011972:Receptor, Insulin / Q000235:genetics / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology*
D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D007328:Insulin; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; C474710:heat shock factor-1, C elegans; C107483:DAF-2 protein, C elegans; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin