Our results show that H2S is an endogenous regulator of oxidative damage, metabolism, and aging in C. elegans and provide new insight into the mechanisms, which control aging in this model organism.

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.

Ageing, a progressive structural and functional decline, is considered to be a major risk factor for virtually all ageing-associated pathologies and disabilities, including Alzheimer's disease, Parkinson's disease, stroke, diabetes, atherosclerosis and certain cancers. Biogerontology research has now been largely directed towards finding novel drug targets to decelerate the ageing process and attain healthy ageing in order to delay the onset of all ageing-related diseases. H2S has been reported to exert vasodilatory, antioxidant, antiapoptotic and anti-inflammatory actions and has been shown to act as a signalling molecule, neuromodulator and cytoprotectant. Intriguingly, H2S has been reported to regulate cell cycle and survival in healthy cells which suggests that it may regulate cell fate and hence the ageing process. This chapter sets out to provide an overview of the current knowledge regarding the involvement of H2S in ageing, with a specific focus on the invertebrate model nematode C. elegans.

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