Krill oil attenuates skeletal muscle atrophy during D-galactose-induced accelerated aging via an AMPK-dependent mechanism

The global aging trend highlights the critical challenge of sarcopenia, which severely compromises both quality of life and overall survival time. This study aimed to investigate the effects of Antarctic krill oil (KO) on accelerated aging-induced skeletal muscle atrophy and its underlying mechanisms. An accelerated aging mouse model was established via daily intraperitoneal injection of 400 mg/kg D-galactose (D-gal) for 12 consecutive weeks. Concurrently, mice received oral gavage of KO or fish oil (FO) at 400 mg/kg once daily. KO treatment mitigated D-gal-induced skeletal muscle atrophy and accelerated aging in mice, as evidenced by the attenuation of D-gal-induced declines in skeletal muscle mass, function, and muscle fiber cross-sectional area, as well as the downregulation of senescence markers. Notably, KO showed superior efficacy to FO. Moreover, KO treatment directly alleviated the D-gal-induced increase in senescence markers in C2C12 myotubes and mitigated the decrease in myotube diameter. Integrated transcriptomic and functional analyses identified AMP-activated protein kinase (AMPK), a master regulator of mitochondrial homeostasis, as a key target of KO in preventing accelerated aging-induced skeletal muscle atrophy. Molecular docking simulations further suggested plausible direct interactions between major KO components and AMPK subunits. Critically, genetic silencing of AMPK abolished the protective effects of KO against D-gal-induced myotube atrophy, as KO failed to improve mitochondrial quality control dysfunction and protein homeostasis. Thus, AMPK is established as the central regulator mediating the anti-sarcopenic actions of KO. Overall, the present study demonstrates that KO is a promising nutraceutical for attenuating accelerated aging-induced skeletal muscle atrophy through an AMPK-dependent mechanism.