Dietary restriction suppresses proteotoxicity and enhances longevity by an hsf-1-dependent mechanism in Caenorhabditis elegans.
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.
Steinkraus
Katherine A
KA
Department of Pathology, University of Washington, Seattle, WA 98195, USA.
Smith
Erica D
ED
Davis
Christina
C
Carr
Daniel
D
Pendergrass
William R
WR
Sutphin
George L
GL
Kennedy
Brian K
BK
Kaeberlein
Matt
M
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*
D029742:Caenorhabditis elegans Proteins; D010455:Peptides; D014157:Transcription Factors; C474710:heat shock factor-1, C elegans; C097188:polyglutamine