C. elegans Aging Is Modulated by Hydrogen Sulfide and the sulfhydrylase/cysteine Synthase cysl-2

Exogenous hydrogen sulfide (H(2)S) administration and endogenous H(2)S metabolism were explored in the nematode C. elegans. Chronic treatment with a slow-releasing H(2)S 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 (H(2)O(2))-induced cell death. Taken together, this provides further support that H(2)S exerts a protective function which is consistent with the longevity dividend theory. Overall, this study underlines the therapeutic potential of a slow-releasing H(2)S donor as regulators of the aging and cellular stress pathways.