Hydrogen sulfide is an endogenous regulator of ageing in Caenorhabditis elegans

Moore, Philip K. and Qabazard, Bedoor and Li, Ling and Gruber, Jan and Ng, Li Fang and Srinivasan, Dinesh Kumar and Rose, Peter and Tan, Choon-Hong and Dymock, Brian William and Wei, Feng and Swain, Suresh and Halliwell, Barry and Sturzenbaum, stephen R and Peh, Meng Teng (2013) Hydrogen sulfide is an endogenous regulator of ageing in Caenorhabditis elegans. Antioxidants & Redox Signaling, n/a . p. 131005150039000. ISSN 1523-0864

Full content URL: http://dx.doi.org/10.1089/ars.2013.5448

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Item Type:Article
Item Status:Live Archive

Abstract

Aims: To investigate the role of endogenous hydrogen sulfide (H2S) in the control of ageing and healthspan of Caenorhabditis elegans. Results: We show that the model organism, C. elegans, synthesizes H2S. Three H2S synthesizing enzymes are present in C. elegans namely cystathionine lyase (CSE), cystathionine synthetase (CBS) and 3-mercaptopyruvate transferase (MPST or 3-MST). Genetic deficiency of mpst-1 (3-MST orthologue 1), but not cth-2 (CSE orthologue) reduced lifespan of C. elegans. This effect was reversed by a pharmacological H2S donor (GYY4137). GYY4137 also reduced detrimental age-dependent changes in a range of physiological indices including pharyngeal contraction and defecation. Treatment of C. elegans with GYY4137 increased the expression of several age-related, stress response and anti-oxidant genes whilst MitoSOX Red fluorescence, indicative of reactive oxygen species generation, was increased in mpst-1 knockouts and decreased by GYY4137 treatment. GYY4137 additionally increased lifespan in short-lived mev-1 mutants with elevated oxidative stress and protected wild type C. elegans against paraquat poisoning. The lifespan-prolonging and health-promoting effects of H2S in C. elegans are likely due to the anti-oxidant action of this highly cell-permeable gas. Conclusion: Our results show that H2S is an endogenous regulator of oxidative damage, metabolism and ageing in C. elegans and provide new insight into the mechanisms which control ageing in this model organism. The possibility that novel pharmacological agents based on the principle of H2S donation may be able to retard the onset of age-related disease by slowing the ageing process warrants further study.

Additional Information:Online Ahead of Print: November 21, 2013 Online Ahead of Editing: October 5, 2013
Keywords:Hydrogen sulfide
Subjects:B Subjects allied to Medicine > B130 Pathology
Divisions:College of Science > School of Life Sciences
ID Code:12429
Deposited On:23 Oct 2013 12:50

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