The relevance of hydrogen sulfide signalling in dietary restriction induced longevity (360G-Wellcome-211618_Z_18_Z)

Dietary restriction (DR), typically reduced food intake relative to ad libitum fed controls, is the most widely used intervention to slow ageing, increase lifespan and healthspan. Precisely how DR acts to induce its effects is unknown, although recent findings suggest that the gasotransmitter hydrogen sulphide (H2S) may underlie the beneficial effects of DR. H2S can also attenuate accelerated ageing phenotypes in progeroid models. In this project I will utilise different strains of ILSXISS mice that show differential responses to DR- from lifespan extension to lifespan shortening. DR-induced longevity in ILSXISS mice is correlated with increased liver H2S production but this is not observed in strains that show lifespan shortening under DR. The key goal of this project is to investigate components of the transulfuration pathway (TSP); the primary pathway in which H2S is synthesised/metabolised within cells. To this end I will measure protein and transcript levels using western blotting and qPCR of key TSP components (e.g. Cystathione- beta-synthase, cystathione-gamma-lyase, rhodanese, sulphide- quinone reductase-like). I will then examine whether commonality exists in these parameters within the liver following DR in ILSXISS mice with comparison with other tissues such as the brain.