Qabazard Bedoor, Li Ling, Gruber Jan, Peh Meng Teng, Ng Li Fang, Kumar Srinivasan Dinesh, Rose Peter, Tan Choon-Hong, Dymock Brian W, Wei Feng, Swain Suresh C, Halliwell Barry, Stürzenbaum Stephen R, Moore Philip K
1 School of Biomedical Science, King's College London, London, United Kingdom .
Antioxid Redox Signal. 2014 Jun 1;20(16):2621-30. doi: 10.1089/ars.2013.5448. Epub 2013 Nov 21.
To investigate the role of endogenous hydrogen sulfide (H2S) in the control of aging and healthspan of Caenorhabditis elegans.
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.
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.
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.
研究内源性硫化氢（H₂S）在秀丽隐杆线虫衰老和健康寿命调控中的作用。
我们发现模式生物秀丽隐杆线虫能够合成H₂S。秀丽隐杆线虫中存在三种H₂S合成酶，即胱硫醚γ裂解酶（CSE）、胱硫醚β合成酶和3-巯基丙酮酸转移酶（MPST或3-MST）。mpst-1（3-MST同源物1）基因缺陷而非cth-2（CSE同源物）会缩短秀丽隐杆线虫的寿命。这种效应可被一种药理学H₂S供体（GYY4137）逆转。GYY4137还减少了一系列生理指标中与年龄相关的有害变化，包括咽部收缩和排便。用GYY4137处理秀丽隐杆线虫可增加几种与年龄相关、应激反应和抗氧化基因的表达，而指示活性氧生成的MitoSOX Red荧光在mpst-1基因敲除中增加，经GYY4137处理后降低。GYY4137还延长了氧化应激升高的短寿命mev-1突变体的寿命，并保护野生型秀丽隐杆线虫免受百草枯中毒。H₂S在秀丽隐杆线虫中延长寿命和促进健康的作用可能归因于这种高度可透过细胞的气体的抗氧化作用。
基于H₂S供体原理的新型药理学药物可能能够通过减缓衰老过程来延缓与年龄相关疾病的发生，这一可能性值得进一步研究。
我们的结果表明，H₂S是秀丽隐杆线虫氧化损伤、代谢和衰老的内源性调节因子，并为该模式生物中控制衰老的机制提供了新的见解。
