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Review
. 2013 Mar;33(6):1104-13.
doi: 10.1128/MCB.01215-12. Epub 2013 Jan 7.

Hydrogen sulfide, the next potent preventive and therapeutic agent in aging and age-associated diseases

Yuan Zhang  1 , Zhi-Han Tang, Zhong Ren, Shun-Lin Qu, Mi-Hua Liu, Lu-Shan Liu, Zhi-Sheng Jiang
Affiliations
Review

Hydrogen sulfide, the next potent preventive and therapeutic agent in aging and age-associated diseases

Yuan Zhang et al. Mol Cell Biol. 2013 Mar.

Abstract

Hydrogen sulfide (H(2)S) is the third endogenous signaling gasotransmitter, following nitric oxide and carbon monoxide. It is physiologically generated by cystathionine-γ-lyase, cystathionine-β-synthase, and 3-mercaptopyruvate sulfurtransferase. H(2)S has been gaining increasing attention as an important endogenous signaling molecule because of its significant effects on the cardiovascular and nervous systems. Substantial evidence shows that H(2)S is involved in aging by inhibiting free-radical reactions, activating SIRT1, and probably interacting with the age-related gene Klotho. Moreover, H(2)S has been shown to have therapeutic potential in age-associated diseases. This article provides an overview of the physiological functions and effects of H(2)S in aging and age-associated diseases, and proposes the potential health and therapeutic benefits of H(2)S.

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Figures

Fig 1
Fig 1
Generation of endogenous H2S. H2S is synthesized by two cytosolic pyridoxal-5′-phosphate-dependent enzymes responsible for the metabolism of l-cysteine, namely, cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE), as well as by the combined action of 3-mercaptopyruvate sulfurtransferase (3-MST) and cysteine aminotransferase (CAT).
Fig 2
Fig 2
H2S exerts its antiaging effects by directly inhibiting free radicals and oxidative stress and by upregulating SIRT1 activity. H2S can directly inhibit the free radicals ROS/RNS and increase inhibitory effects of GSH and SOD on ROS production and redox enzyme levels to increase cellular stress resistance, which is correlated with extended organismal longevity. CR and resveratrol have been reported to have antiaging properties. CR and resveratrol share similar antiaging mechanisms: they both increase SIRT1 expression to inhibit oxidative stress or to play antiapoptotic roles. Resveratrol can also ameliorate age-related metabolic phenotypes by inhibiting cAMP phosphodiesterases (PDE). Similarly, H2S has been reported to enhance the activity of SIRT1 and to inhibit PDE activity. As shown in the figure, H2S may have antiaging functions through several shared pathways related to CR and resveratrol.
Fig 3
Fig 3
H2S may have an effect on the age-related gene Klotho to promote longevity. Klotho can improve longevity by inhibiting IIS signaling, inducing FOXO derepression, and decreasing angiotensin II-induced oxidative stress, among other effects. However, angiotensin II may downregulate the expression of Klotho. Interestingly, H2S exhibits direct inhibitory action on ACE activity, which catalyzes the conversion of angiotensin I to angiotensin II. Moreover, H2S can decrease the binding affinity between angiotensin II and AT1 receptor and can inhibit renin activity, which participates in the renin-angiotensin system. Hence, H2S may improve Klotho expression to promote longevity via negative regulation of angiotensin II production.
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