The hydrogen sulfide signaling system: changes during aging and the benefits of caloric restriction

Hydrogen sulfide gas (H2S) is a putative signaling molecule that causes diverse effects in mammalian tissues including relaxation of blood vessels and regulation of perfusion in the liver, but the effects of aging on H2S signaling are unknown. Aging has negative impacts on the cardiovascular system. However, the liver is more resilient with age. Caloric restriction (CR) attenuates affects of age in many tissues. We hypothesized that the H2S signaling system is negatively affected by age in the vasculature but not in the liver, which is typically more resilient to age, and that a CR diet minimizes the age affect in the vasculature. To investigate this, we determined protein and mRNA expression of the H2S-producing enzymes cystathionine gamma-lyase (CSE) and cystathionine beta-synthase (CBS), H2S production rates in the aorta and liver, and the contractile response of aortic rings to exogenous H2S. Tissue was collected from Fisher 344 x Brown Norway rats from 8-38 months of age, which had been maintained on an ad libitum (AL) or CR diet. The results demonstrate that age and diet have differential effects on the H2S signaling system in aorta and liver. The aorta showed a sizeable effect of both age and diet, whereas the liver only showed a sizeable effect of diet. Aortic rings showed increased contractile sensitivity to H2S and increased protein expression of CSE and CBS with age, consistent with a decrease in H2S concentration with age. CR appears to benefit CSE and CBS protein in both aorta and liver, potentially by reducing oxidative stress and ameliorating the negative effect of age on H2S concentration. Therefore, CR may help maintain the H2S signaling system during aging.