Multimodal cell atlas of the ageing human skeletal muscle

Yiwei Lai, Ignacio Ramírez-Pardo, Joan Isern, Juan An, Eusebio Perdiguero, Antonio L. Serrano, Jinxiu Li, Esther García-Domínguez, Jessica Segalés, Pengcheng Guo, Vera Lukesova, Eva Andrés, Jing Zuo, Yue Yuan, Chuanyu Liu, José Viña, Julio Doménech-Fernández, Mari Carmen Gómez-Cabrera, Yancheng Song, Longqi Liu, Xun Xu, Pura Muñoz-Cánoves & Miguel A. Esteban.
Nature. 2024-04-22;
Muscle atrophy and functional decline (sarcopenia) are common manifestations of frailty and are critical contributors to morbidity and mortality in older people1. Deciphering the molecular mechanisms underlying sarcopenia has major implications for understanding human ageing2. Yet, progress has been slow, partly due to the difficulties of characterizing skeletal muscle niche heterogeneity (whereby myofibres are the most abundant) and obtaining well-characterized human samples3,4. Here we generate a single-cell/single-nucleus transcriptomic and chromatin accessibility map of human limb skeletal muscles encompassing over 387,000 cells/nuclei from individuals aged 15 to 99 years with distinct fitness and frailty levels. We describe how cell populations change during ageing, including the emergence of new populations in older people, and the cell-specific and multicellular network features (at the transcriptomic and epigenetic levels) associated with these changes. On the basis of cross-comparison with genetic data, we also identify key elements of chromatin architecture that mark susceptibility to sarcopenia. Our study provides a basis for identifying targets in the skeletal muscle that are amenable to medical, pharmacological and lifestyle interventions in late life.

Related data

Data summary
All raw data have been deposited to CNGB Nucleotide Sequence Archive (CNP0004394, CNP0004395, CNP0004494 and CNP0004495). The data deposited and made public is compliant with the regulations of the Ministry of Science and Technology of the People’s Republic of China. Source data are provided with this paper.
Data summary
All processed data are available at the Human Muscle Ageing Cell Atlas database.
Data summary
All data were analysed using standard programs and packages, as described in the Methods. Custom code supporting the current study was created for the processing of the sequencing data49.
Data summary
Analysis of the generated data82.