Cell atlas of the ageing human skeletal muscle - Europe RNA

Muscle atrophy and frailty are common manifestations of sarcopenia and are critical contributors to morbidity and mortality in the elderly. Deciphering the underlying molecular mechanisms of sarcopenia has major implications for understanding human ageing, yet progress has been slow, in part due to the complexity of characterizing skeletal muscle niche heterogeneity (with myofibres being more abundant) and the difficulty of accessing well-characterized human samples. Here, we have generated a single-cell/single-nucleus transcriptomic and chromatin accessibility map of human limb skeletal muscles encompassing over 387,000 cells/nuclei from individuals ranging from 15 to 99 years of age with distinct fitness and frailty levels. We describe i) the changes in cell populations during distinct ages, including the emergence of new ones in the elderly, and ii) the cell-specific and multicellular network features (at the transcriptomic and epigenetic levels) that are associated with these changes. Based on cross-comparison with genetic data, we also identify key elements of chromatin architecture marking susceptibility to sarcopenia. Our study provides the basis for the identification of novel targets in the skeletal muscle amenable to medical, pharmacological and lifestyle interventions in late life.