Hydrogen sulfide is an endogenous regulator of aging in Caenorhabditis elegans
Aims: To investigate the role of endogenous hydrogen sulfide (H2S) in the control of aging 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 γ lyase (CSE), cy...
| Main Authors: | , , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2014
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| Subjects: | |
| Online Access: | https://hdl.handle.net/10356/103725 http://hdl.handle.net/10220/19282 |
| _version_ | 1811686873255378944 |
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| author | Qabazard, Bedoor Li, Ling Gruber, Jan Peh, Meng Teng Ng, Li Fang Dinesh Kumar, Srinivasan Rose, Peter Tan, Choon-Hong Dymock, Brian W. Wei, Feng Swain, Suresh C. Halliwell, Barry Stürzenbaum, Stephen R. Moore, Philip K. |
| author2 | Lee Kong Chian School of Medicine (LKCMedicine) |
| author_facet | Lee Kong Chian School of Medicine (LKCMedicine) Qabazard, Bedoor Li, Ling Gruber, Jan Peh, Meng Teng Ng, Li Fang Dinesh Kumar, Srinivasan Rose, Peter Tan, Choon-Hong Dymock, Brian W. Wei, Feng Swain, Suresh C. Halliwell, Barry Stürzenbaum, Stephen R. Moore, Philip K. |
| author_sort | Qabazard, Bedoor |
| collection | NTU |
| description | Aims: To investigate the role of endogenous hydrogen sulfide (H2S) in the control of aging 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 γ lyase (CSE), cystathionine β synthetase, and 3-mercaptopyruvate transferase (MPST or 3-MST). Genetic deficiency of mpst-1 (3-MST orthologue 1), but not cth-2 (CSE orthologue), reduced the 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 antioxidant genes, whereas MitoSOX Red fluorescence, indicative of reactive oxygen species generation, was increased in mpst-1 knockouts and decreased by GYY4137 treatment. GYY4137 additionally increased the 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 antioxidant action of this highly cell-permeable gas. Innovation: 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 aging process warrants further study. Conclusion: 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. Antioxid. Redox Signal. 00, 000–000. |
| first_indexed | 2024-10-01T05:07:20Z |
| format | Journal Article |
| id | ntu-10356/103725 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T05:07:20Z |
| publishDate | 2014 |
| record_format | dspace |
| spelling | ntu-10356/1037252022-02-16T16:28:08Z Hydrogen sulfide is an endogenous regulator of aging in Caenorhabditis elegans Qabazard, Bedoor Li, Ling Gruber, Jan Peh, Meng Teng Ng, Li Fang Dinesh Kumar, Srinivasan Rose, Peter Tan, Choon-Hong Dymock, Brian W. Wei, Feng Swain, Suresh C. Halliwell, Barry Stürzenbaum, Stephen R. Moore, Philip K. Lee Kong Chian School of Medicine (LKCMedicine) DRNTU::Science::Medicine Aims: To investigate the role of endogenous hydrogen sulfide (H2S) in the control of aging 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 γ lyase (CSE), cystathionine β synthetase, and 3-mercaptopyruvate transferase (MPST or 3-MST). Genetic deficiency of mpst-1 (3-MST orthologue 1), but not cth-2 (CSE orthologue), reduced the 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 antioxidant genes, whereas MitoSOX Red fluorescence, indicative of reactive oxygen species generation, was increased in mpst-1 knockouts and decreased by GYY4137 treatment. GYY4137 additionally increased the 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 antioxidant action of this highly cell-permeable gas. Innovation: 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 aging process warrants further study. Conclusion: 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. Antioxid. Redox Signal. 00, 000–000. Published version 2014-04-30T08:23:52Z 2019-12-06T21:18:53Z 2014-04-30T08:23:52Z 2019-12-06T21:18:53Z 2013 2013 Journal Article Qabazard, B., Li, L., Gruber, J., Peh, M. T., Ng, L. F., Dinesh Kumar, S., Rose, P., Tan, C. H., Dymock, B. W., Wei, F., Swain, S. C., Halliwell, B., Stürzenbaum, S. R., & Moore, P. K. (2013). Hydrogen Sulfide Is an Endogenous Regulator of Aging in Caenorhabditis elegans. Antioxidants & Redox Signaling, 131121072603008-. 1523-0864 https://hdl.handle.net/10356/103725 http://hdl.handle.net/10220/19282 10.1089/ars.2013.5448 24093496 en Antioxidants & redox signaling © 2013 Mary Ann Liebert, Inc. This paper was published in Antioxidants & Redox Signaling and is made available as an electronic reprint (preprint) with permission of Mary Ann Liebert. The paper can be found at the following official DOI: [http://dx.doi.org/10.1089/ars.2013.5448]. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper is prohibited and is subject to penalties under law. 10 p. application/pdf |
| spellingShingle | DRNTU::Science::Medicine Qabazard, Bedoor Li, Ling Gruber, Jan Peh, Meng Teng Ng, Li Fang Dinesh Kumar, Srinivasan Rose, Peter Tan, Choon-Hong Dymock, Brian W. Wei, Feng Swain, Suresh C. Halliwell, Barry Stürzenbaum, Stephen R. Moore, Philip K. Hydrogen sulfide is an endogenous regulator of aging in Caenorhabditis elegans |
| title | Hydrogen sulfide is an endogenous regulator of aging in Caenorhabditis elegans |
| title_full | Hydrogen sulfide is an endogenous regulator of aging in Caenorhabditis elegans |
| title_fullStr | Hydrogen sulfide is an endogenous regulator of aging in Caenorhabditis elegans |
| title_full_unstemmed | Hydrogen sulfide is an endogenous regulator of aging in Caenorhabditis elegans |
| title_short | Hydrogen sulfide is an endogenous regulator of aging in Caenorhabditis elegans |
| title_sort | hydrogen sulfide is an endogenous regulator of aging in caenorhabditis elegans |
| topic | DRNTU::Science::Medicine |
| url | https://hdl.handle.net/10356/103725 http://hdl.handle.net/10220/19282 |
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