Multicellular senescence impairs skeletal muscle recovery following disuse in aging

Although muscle regrowth requires coordinated interactions between immune and progenitor cells, the mechanisms of impaired remodeling in aged skeletal muscle remain poorly understood, yet possibly involving the accumulation of senescent cells. We used a novel flow cytometry approach coupled with scRNAseq to determine the muscle senescent cell identity and transcriptional landscape during skeletal muscle recovery following disuse atrophy.

Young and aged mice underwent 14d of hindlimb unloading followed by reloading (7 or 14d). At recovery, old mice showed smaller myofibers and abnormal muscle macrophage dynamics corresponding to greater collagen content. These outcomes coincided with elevated markers of muscle senescence (p21, γH2AX) and increased SPiDER-β-Gal⁺ cells, which inversely correlated with muscle mass.