Hydrogen sulfide (H_2S) is naturally produced in animal cells. Exogenous H_2S 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 H_2S to elucidate the molecular mechanisms of H_2S action. Here we show that nematodes exposed to H_2S are apparently healthy and do not exhibit phenotypes consistent with metabolic inhibition. Instead, animals exposed to H_2S are thermo-tolerant 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 H_2S 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 H_2S.
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