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Steinkraus, K. A. et al. Dietary restriction suppresses proteotoxicity and enhances longevity by an hsf-1-dependent mechanism in Caenorhabditis elegans. Aging Cell 7, 394-404

Department of Pathology, University of Washington, Seattle, WA 98195, USA.
Aging cell (Impact Factor: 5.94). 07/2008; 7(3):394-404. DOI: 10.1111/j.1474-9726.2008.00385.x
Source: PubMed

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.

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Available from: George L Sutphin, Mar 17, 2014
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    • "Using BDR and the eat-2 mutant, Bishop and Guarente (2007) showed that the transcription factor SKN-1 in the ASI neurons is indispensable and other transcriptional regulators, such as PHA-4, HIF-1, HSF-1 and CBP-1 were identified as important players mediating the DR effect (Chen et al., 2009; Panowski et al., 2007; Steinkraus et al., 2008; Zhang et al., 2009). Furthermore, other genes, including the energy sensor aak-2 (Greer et al., 2007) and two downstream targets of SKN-1, cup-4 and nlp-7 (Park et al., 2010) are involved in the lifespanextending effect of DR. "
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    • "What will be the functional significance of up-regulation of HSF-1 activity by reduced TOR signaling? A previous report showed that dietary restriction increases lifespan and enhances resistance to polyglutamine aggregation in an hsf-1-dependent manner (Steinkraus et al., 2008). As dietary restriction reduces TOR signaling (Kaeberlein & Kennedy, 2011), it seems likely that dietary restriction promotes longevity and stress resistance via inhibiting TOR signaling and subsequently increasing HSF-1 activity. "
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