Multiomics reveals glutathione metabolism as a driver of bimodality during stem cell aging.

ABSTRACT: With age, skeletal muscle stem cells (MuSCs) activate out of quiescence more slowly and with increased death, leading to defective muscle repair. To explore the molecular underpinnings of these defects, we combined multiomics, single-cell measurements, and functional testing of MuSCs from young and old mice. The multiomics approach allowed us to assess which changes are causal, which are compensatory, and which are simply correlative. We identified glutathione (GSH) metabolism as perturbed in old MuSCs, with both causal and compensatory components. Contrary to young MuSCs, old MuSCs exhibit a population dichotomy composed of GSH^high cells (comparable with young MuSCs) and GSH^low cells with impaired functionality. Mechanistically, we show that antagonism between NRF2 a

SUBMITTER: Benjamin DI 

PROVIDER: S-EPMC10015599 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature