title: C. elegans aging is modulated by hydrogen sulfide and the sulfhydrylase/cysteine synthase cysl-2.
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.
authors.affiliation: School of Biomedical Sciences, King's College London, London, United Kingdom.
authors.forename: Bedoor
authors.initials: B
authors.lastname: Qabazard
authors.forename: Samanza
authors.initials: S
authors.lastname: Ahmed
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.forename: Volker M
authors.initials: VM
authors.lastname: Arlt
authors.forename: Philip K
authors.initials: PK
authors.lastname: Moore
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Stürzenbaum
mesh_terms: D000375:Aging / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D002417:Cattle; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003547:Cysteine Synthase / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D006861:Hydrogen Peroxide / Q000378:metabolism; D006862:Hydrogen Sulfide / Q000378:metabolism* / Q000494:pharmacology*; D009025:Morpholines / Q000494:pharmacology; D009946:Organothiophosphorus Compounds / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: C529376:GYY 4137; D009025:Morpholines; D009946:Organothiophosphorus Compounds; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D003547:Cysteine Synthase; D006862:Hydrogen Sulfide