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

作者：Steinkraus Katherine A; Smith Erica D; Davis Christina; Carr Daniel; Pendergrass William R; Sutphin George L; Kennedy Brian K; Kaeberlein Matt^*

来源：AGING CELL, 2008, 7(3): 394-404.

DOI：10.1111/j.1474-9726.2008.00385.x

• Caenorhabditis elegans
• dietary restriction
• hsf-1
• longevity
• proteotoxicitys

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.

• 出版日期2008-6