| HRA004792
(Controlled Access)
|
Muscle atrophy and frailty are common manifestations of sarcopenia and are critical contributors to morbidity and mortality in the elderly. Yet, progress has been slow. 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 ageing, including the emergence of new ones in the elderly, and ii) the cell-specific and multicellular network features (at the transcriptomic and epigenetic levels) 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 discovery of novel targets in the skeletal muscle amenable to medical, pharmacological, and lifestyle interventions in late life. |
