A noncanonical cGAS-STING pathway drives cellular and organismal aging.

ABSTRACT: Accumulation of cytosolic DNA has emerged as a hallmark of aging, inducing sterile inflammation. Stimulator of interferon genes (STING) protein translates the sensing of cytosolic DNA by cyclic-GMP-AMP synthase (cGAS) into an inflammatory response. However, the molecular mechanisms whereby cytosolic DNA-induced cGAS-STING pathway leads to aging remain poorly understood. We show that STING does not follow the canonical pathway of activation in human fibroblasts passaged (aging) in culture, senescent fibroblasts, or progeria fibroblasts (from Hutchinson-Gilford progeria syndrome patients). Despite cytosolic DNA buildup, features of the canonical cGAS-STING pathway like increased cGAMP production, STING phosphorylation, and STING trafficking to perinuclear compartment are not observed in prog

SUBMITTER: Cancado de Faria R 

PROVIDER: S-EPMC12280946 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature