Is there a role of H2S in mediating health span benefits of caloric restriction?

Abstract

Caloric restriction (CR) is a dietary regimen that aims to reduce the intake of total calories while maintaining adequate supply of key nutrients so as to avoid malnutrition. CR is one of only a small number of interventions that show promising outcomes on health span and lifespan across different species. There is growing interest in the development of compounds that might replicate CR-related benefits without actually restricting food intake. Hydrogen sulfide (H₂S) is produced inside the bodies of many animals, including humans, by evolutionarily conserved H₂S synthesizing enzymes. Endogenous H₂S is increasingly recognized as an important gaseous signalling molecule involved in diverse cellular and molecular processes. However, the specific role of H₂S in diverse biological processes remains to be elucidated and not all its biological effects are beneficial. Nonetheless, recent evidence suggests that the biological functions of H₂S intersect with the network of evolutionarily conserved nutrient sensing and stress response pathways that govern organismal responses to CR. Induction of H₂S synthesizing enzymes appears to be a conserved and essential feature of the CR response in evolutionarily distant organisms, including nematodes and mice. Here we review the evidence for a role of H₂S in CR and lifespan modulation. H₂S releasing drugs, capable of controlled delivery of exogenous H₂S, are currently in clinical development. These findings suggest such H₂S releasing drugs as a promising novel avenue for the development of CR mimetic compounds.

Keywords: Ageing; Caloric restriction; Health span; Hydrogen sulfide; Lifespan.