MtDNA release promotes cGAS-STING activation and accelerated aging of postmitotic muscle cells.

ABSTRACT: The mechanism regulating cellular senescence of postmitotic muscle cells is still unknown. cGAS-STING innate immune signaling was found to mediate cellular senescence in various types of cells, including postmitotic neuron cells, which however has not been explored in postmitotic muscle cells. Here by studying the myofibers from Zmpste24^-/- progeria aged mice [an established mice model for Hutchinson-Gilford progeria syndrome (HGPS)], we observed senescence-associated phenotypes in Zmpste24^-/- myofibers, which is coupled with increased oxidative damage to mitochondrial DNA (mtDNA) and secretion of senescence-associated secretory phenotype (SASP) factors. Also, Zmpste24^-/- myofibers feature increased release of mtDNA from damaged mitochondria, mitophagy dysf

SUBMITTER: Li Y 

PROVIDER: S-EPMC11263593 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature