Dnmt3a overexpression disrupts skeletal muscle homeostasis, promotes an aging-like phenotype, and reduces metabolic elasticity.

ABSTRACT: Mammalian aging is reportedly driven by the loss of epigenetic information; however, its impact on skeletal muscle aging remains unclear. This study shows that aging mouse skeletal muscle exhibits increased DNA methylation, and overexpression of DNA methyltransferase 3a (Dnmt3a) induces an aging-like phenotype. Muscle-specific Dnmt3a overexpression leads to an increase in central nucleus-positive myofibers, predominantly in fast-twitch fibers, a shift toward slow-twitch fibers, elevated inflammatory and senescence markers, mitochondrial OXPHOS complex I reduction, and decreased basal autophagy. Dnmt3a overexpression resulted in reduced muscle mass and strength and impaired endurance exercise capacity with age, accompanied by an enhanced inflammatory signature. In addition, Dnmt3a overexpre

SUBMITTER: Oyabu M 

PROVIDER: S-EPMC11937683 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature