title: Dietary restriction suppresses proteotoxicity and enhances longevity by an hsf-1-dependent mechanism in Caenorhabditis elegans.
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.
authors.affiliation: Department of Pathology, University of Washington, Seattle, WA 98195, USA.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Steinkraus
authors.forename: Erica D
authors.initials: ED
authors.lastname: Smith
authors.forename: Christina
authors.initials: C
authors.lastname: Davis
authors.forename: Daniel
authors.initials: D
authors.lastname: Carr
authors.forename: William R
authors.initials: WR
authors.lastname: Pendergrass
authors.forename: George L
authors.initials: GL
authors.lastname: Sutphin
authors.forename: Brian K
authors.initials: BK
authors.lastname: Kennedy
authors.forename: Matt
authors.initials: M
authors.lastname: Kaeberlein
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000187:drug effects / Q000378:metabolism*; D031204:Caloric Restriction; D005508:Food Deprivation / Q000502:physiology; D008136:Longevity / Q000187:drug effects / Q000502:physiology*; D010455:Peptides / Q000494:pharmacology; D014157:Transcription Factors / Q000187:drug effects / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D010455:Peptides; D014157:Transcription Factors; C474710:heat shock factor-1, C elegans; C097188:polyglutamine