Heat shock and caloric restriction have a synergistic effect on the heat shock response in a sir2.1-dependent manner in Caenorhabditis elegans.
The heat shock response (HSR) is responsible for maintaining cellular and organismal health through the regulation of proteostasis. Recent data demonstrating that the mammalian HSR is regulated by SIRT1 suggest that this response may be under metabolic control. To test this hypothesis, we have determined the effect of caloric restriction in Caenorhabditis elegans on activation of the HSR and have found a synergistic effect on the induction of hsp70 gene expression. The homolog of mammalian SIRT1 in C. elegans is Sir2.1. Using a mutated C. elegans strain with a sir2.1 deletion, we show that heat shock and caloric restriction cooperate to promote increased survivability and fitness in a sir2.1-dependent manner. Finally, we show that caloric restriction increases the ability of heat shock to preserve movement in a polyglutamine toxicity neurodegenerative disease model and that this effect is dependent on sir2.1.
Department of Cell Biology, Microbiology and Molecular Biology, College of Arts and Sciences, University of South Florida, Tampa, Florida 33620, USA.
Rachel
R
Raynes
Bruce D
BD
Leckey
Kevin
K
Nguyen
Sandy D
SD
Westerheide
D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D031204:Caloric Restriction; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000502:physiology*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D018869:Heat-Shock Response / Q000502:physiology*; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; D018840:HSP70 Heat-Shock Proteins; D010455:Peptides; C097188:polyglutamine; C507014:SIR-2.1 protein, C elegans; D037761:Sirtuins