Characterization of the impact of GMP/GDP synthesis inhibition on replicative lifespan extension in yeast.

ABSTRACT: Slowing down aging-associated accumulation of molecular damage or its prevention represents a promising therapeutic paradigm to combat aging-related disease and death. While several chemical compounds extend lifespan in model organisms, their mechanism of action is often unknown, reducing their therapeutic potential. Using a systematic approach, here we characterize the impact of the GMP pathway on yeast lifespan and elucidate GMP synthesis inhibition as a lifespan extension mechanism. We further discover that proteasome activation extends lifespan in part through the GMP pathway. GMP synthesis inhibition exerts its lifespan extension effect independently of the canonical nutrient-sensing pathway regulating lifespan. Exposing longitudinally aging yeast cells to GMP pathway inhibition in an

SUBMITTER: Liu P 

PROVIDER: S-EPMC7367712 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature