Abstract
Exogenous hydrogen sulfide (H2S) administration and endogenous H2S metabolism were explored in the nematode C. elegans. Chronic treatment with a slow-releasing H2S donor, GYY4137, extended median survival by 17-23% and increased tolerance towards oxidative and endoplasmic reticulum (ER) stress. Also, cysl-2, a sulfhydrylase/cysteine synthase in C. elegans, was transcriptionally upregulated by GYY4137 treatment and the deletion of cysl-2 resulted in a significant reduction in lifespan which was partially recovered by the supplementation of GYY4137. Likewise, a mammalian cell culture system, GYY4137 was able to protect bovine aortic endothelial cells (BAECs) from oxidative stress and (H2O2)-induced cell death. Taken together, this provides further support that H2S exerts a protective function which is consistent with the longevity dividend theory. Overall, this study underlines the therapeutic potential of a slow-releasing H2S donor as regulators of the aging and cellular stress pathways.
Highlights
Hydrogen sulfide (H2S), historically associated with the pungent odour of the naturally occurring gas, has recently attracted extensive attention for its multiple physiological functions and potential contribution to pathological states
The true concentration of H2S in C. elegans cells under our experimental conditions remains unknown as techniques for the accurate intracellular measurement of H2S in nematodes have yet to be developed
A remarkable attenuation of the basal H2O2 level was observed in GYY4137treated worms compared to untreated controls (Figure 1A), suggesting a novel antioxidative mechanism of GYY4137
Summary
Hydrogen sulfide (H2S), historically associated with the pungent odour of the naturally occurring gas, has recently attracted extensive attention for its multiple physiological functions and potential contribution to pathological states. H2S has been reported to regulate cell cycle and survival in healthy cells [7] suggesting it may play a role in cell fate and the aging process. The “longevity dividend approach” states that any delay of the aging process may postpone the onset of all aging-related diseases [8]. Given that the monitoring of complete survival profiles in humans is challenging, model organisms such as the nematode Caenorhabditis elegans are valuable surrogates, and arguably the premier animal model for aging research. Previous work reports that the exposure to low concentrations of H2S gas result in the extension of the nematodes lifespan [9]
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