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

Abstract

Hydrogen sulfide gas (H 2 S) 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 H 2 S 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 H 2 S 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 H 2 S-producing enzymes cystathionine γ-lyase (CSE) and cystathionine β-synthase (CBS), H 2 S production rates in the aorta and liver, and the contractile response of aortic rings to exogenous H 2 S. Tissue was collected from Fisher 344×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 H 2 S 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 H 2 S and increased protein expression of CSE and CBS with age, consistent with a decrease in H 2 S 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 H 2 S concentration. Therefore, CR may help maintain the H 2 S signaling system during aging.

Hydrogen Sulfide, the Next Potent Preventive and Therapeutic Agent in Aging and Age-Associated Diseases

“…CR also has potential benefits for CSE and CBS in both the aorta and liver by reducing oxidative stress and ameliorating the negative effect of age on H 2 S concentration. Consistent with this, Predmore et al inferred from their study that CR may help maintain the H 2 S signaling system during aging (54). CR and H 2 S apparently have a synergistic antiaging effect by regulating SIRT1 activity.…”

Phosphinodithioate and Phosphoramidodithioate Hydrogen Sulfide Donors

“…It has been known for some time that blood and tissue levels of "H 2 S" decline with age Predmore et al 2010), and up until recently , there was no mechanism to replace the loss of this gas. Qazabard et al (2014) were the first to investigate the effects of GYY4137 in a well-established model of whole animal ageing using Caenorhabditis elegans.…”

H2S: A New Approach to Lifespan Enhancement and Healthy Ageing?

“…H 2 S replacement promotes endothelial protection in hyperglycaemia due to the preservation of mitochondrial function (Suzuki et al 2011). Likewise, the protective effect of calorie restriction in blood vessels of ageing rats has been attributed to the maintenance of normal H 2 S levels (Predmore et al 2010). Moreover, the suggested antioxidant role of H 2 S seems to align well with the free radical theory of ageing and may contribute to its therapeutic potential in ageing-associated diseases, such as AD, PD, atherosclerosis and others.…”