Hydrogen sulfide increases thermotolerance and lifespan in Caenorhabditis elegans

  1. Dana L. Miller and
  2. Mark B. Roth*
  1. Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109
  1. Communicated by Steven L. McKnight, University of Texas Southwestern Medical Center, Dallas, TX, October 26, 2007 (received for review May 9, 2007)

Abstract

Hydrogen sulfide (H2S) is naturally produced in animal cells. Exogenous H2S has been shown to effect physiological changes that improve the capacity of mammals to survive in otherwise lethal conditions. However, the mechanisms required for such alterations are unknown. We investigated the physiological response of Caenorhabditis elegans to H2S to elucidate the molecular mechanisms of H2S action. Here we show that nematodes exposed to H2S are apparently healthy and do not exhibit phenotypes consistent with metabolic inhibition. Instead, animals exposed to H2S are thermotolerant and long-lived. These phenotypes require SIR-2.1 activity but are genetically independent of the insulin signaling pathway, mitochondrial dysfunction, and caloric restriction. These studies suggest that SIR-2.1 activity may translate environmental change into physiological alterations that improve survival. It is interesting to consider the possibility that the mechanisms by which H2S increases thermotolerance and lifespan in nematodes are conserved and that studies using C. elegans may help explain the beneficial effects observed in mammals exposed to H2S.

Footnotes

  • *To whom correspondence should be addressed. E-mail: mroth{at}fhcrc.org
  • Author contributions: D.L.M. and M.B.R. designed research; D.L.M. performed research; D.L.M. analyzed data; and D.L.M. and M.B.R. wrote the paper.

  • Conflict of interest statement: The authors acknowledge a potential conflict of interest in that both authors are named as inventors on at least one patent that was licensed to a private company, founded by Mark Roth, to commercialize this technology.

  • This article contains supporting information online at www.pnas.org/cgi/content/full/0710191104/DC1.

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