Human in vitro skeletal muscle models recapitulate age-related atrophy and contractile decline induced by aged serum

Age-related skeletal muscle atrophy and the accompanying decline in muscle strength represent major societal challenges, highlighting the urgent need to identify bioactive compounds that can prevent such deterioration. Although in vitro muscle models are valuable tools for evaluating the effects of candidate compounds, a human in vitro system that faithfully reproduces age-related muscle atrophy and functional loss has not yet been established. This study established a human in vitro aged muscle model and examined whether quercetin, a dietary polyphenol, could alleviate atrophic and functional effects induced by aged human serum. Primary human myoblasts were cultured and treated with serum from healthy young or older individuals for 48 h. Exposure to aged serum reduced the MF20-positive cell area in the 2D model and diminished contractile force in the 3D model. Further analyses revealed that aged serum treatment upregulated muscle-specific E3 ubiquitin ligases, mainly through activation of NF-κB signaling. Quercetin also suppressed NF-κB activation and mitigated aged serum-induced muscle atrophy and contractile dysfunction. Together, these findings demonstrate the effectiveness of quercetin and confirm the establishment of a human in vitro model of age-related muscle atrophy.