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: 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.