Authors: Steinkraus KA; Smith ED; Davis C; Carr D; Pendergrass WR; Sutphin GL; Kennedy BK; Kaeberlein M
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.Keywords: Animals; Caenorhabditis elegans/drug effects/genetics/*metabolism; Caenorhabditis elegans Proteins/drug effects/*metabolism; *Caloric Restriction; Food Deprivation/physiology; Longevity/drug effects/*physiology; Peptides/pharmacology; Transcription Factors/drug effects/*metabolism
Journal: Aging cell
Date: March 12, 2008
Steinkraus KA, Smith ED, Davis C, Carr D, Pendergrass WR, Sutphin GL, Kennedy BK, Kaeberlein M (2008) Dietary restriction suppresses proteotoxicity and enhances longevity by an hsf-1-dependent mechanism in Caenorhabditis elegans. Aging cell 7: 394-404.