Dietary restriction suppresses proteotoxicity and enhances longevity by an hsf-1-dependent mechanism in Caenorhabditis elegans

Katherine A. Steinkraus, Erica D. Smith, Christina Davis, Daniel Carr, William R. Pendergrass, George L. Sutphin, Brian K. Kennedy, Matt Kaeberlein*

*Corresponding author for this work

Research output: Contribution to journalArticle

157 Scopus citations

Abstract

Dietary restriction increases lifespan and slows the onset of age-associated disease in organisms from yeast to mammals. In humans, several age-related diseases are associated with aberrant protein folding or aggregation, including neurodegenerative disorders such as Alzheimer's, Parkinson's, and Huntington's diseases. We report here that dietary restriction dramatically suppresses age-associated paralysis in three nematode models of proteotoxicity. Similar to its longevity-enhancing properties, dietary restriction protects against proteotoxicity by a mechanism distinct from reduced insulin/IGF-1-like signaling. Instead, the heat shock transcription factor, hsf-1, is required for enhanced thermotolerance, suppression of proteotoxicity, and lifespan extension by dietary restriction. These findings demonstrate that dietary restriction confers a general protective effect against proteotoxicity and promotes longevity by a mechanism involving hsf-1.

Original languageEnglish (US)
Pages (from-to)394-404
Number of pages11
JournalAging Cell
Volume7
Issue number3
DOIs
StatePublished - Jun 2008

Keywords

  • Caenorhabditis elegans
  • Dietary restriction
  • Longevity
  • Proteotoxicitys
  • hsf-1

ASJC Scopus subject areas

  • Aging
  • Cell Biology

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    Steinkraus, K. A., Smith, E. D., Davis, C., Carr, D., Pendergrass, W. R., Sutphin, G. L., Kennedy, B. K., & Kaeberlein, M. (2008). Dietary restriction suppresses proteotoxicity and enhances longevity by an hsf-1-dependent mechanism in Caenorhabditis elegans. Aging Cell, 7(3), 394-404. https://doi.org/10.1111/j.1474-9726.2008.00385.x