Single‐Nucleus <scp>RNA</scp> Sequencing Reveals Muscle Fiber Cell Heterogeneity During Human Skeletal Muscle Aging

hybrid fibers exhibited features of fatty infiltration, correlated with an expansion of fibro/adipogenic progenitors (FAPs). Pseudotime trajectory analysis supported the progression from young to degenerative or adipogenic fates. The aged microenvironment was globally altered, featuring impaired metabolic activity in muscle stem cells, compromised immune surveillance and function decline of vascular compartments. Critically, cell-cell communication analysis revealed enhanced BMP and Laminin signaling from FAPs to myofibers in aged tissue. Our work provided a high-resolution roadmap of human skeletal muscle aging, establishing denervation and FAP-driven fatty infiltration as key cellular mechanisms driving functional decline, and revealing novel targets for therapeutic intervention.