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.
Muscle atrophy and functional decline are common manifestations of frailty and are critical contributors to morbidity and mortality in older people. Yet, progress has been slow, partly due to the difficulties of characterizing skeletal muscle niche heterogeneity and obtaining well-characterized human samples.
Skeletal muscle comprises large multinucleated myofibres with distinct contractile and metabolic activities controlled by the activity of motoneurons that contact the myofibres at the neuromuscular junction . Muscles also contain a variety of less abundant mononucleated cells, including muscle stem cells , fibro-adipogenic progenitors , adipocytes, fibroblast-like cells, immune cells, vascular cells and Schwann cells.
Here we aimed to generate a comprehensive transcriptomic and epigenomic cell atlas of the human locomotor skeletal muscle across different age groups and sexes, including individuals aged ≥84 years with signs of sarcopenia.To investigate the molecular changes that occur in the human skeletal muscle with ageing, we obtained hindlimb muscle biopsies from 31 participants from Spain and China, who were divided into two age groups: adults .
Gonzalez‐Freire, M. et al. Skeletal muscle ex vivo mitochondrial respiration parallels decline in vivo oxidative capacity, cardiorespiratory fitness, and muscle strength: The Baltimore Longitudinal Study of Aging.MacQuarrie, K. L. et al. Comparison of genome-wide binding of MyoD in normal human myogenic cells and rhabdomyosarcomas identifies regional and local suppression of promyogenic transcription factors.Rigillo, G. et al.
P.M.-C. and M.A.E. supervised the study. Y.L., I.R.-P., J.I., E.P., A.L.S., P.M.-C. and M.A.E. conceptualized the study and wrote the manuscript. Y.L., I.R.-P., J.A., A.L.S., J.S., P.G., V.L. and E.A. performed the experiments. Y.L., I.R.-P., J.A. and J.L. analysed the data. E.G.-D., J.V., J.D.-F, M.C.G.-C. and Y.S. collected the muscle biopsies. J.Z., Y.Y. and C.L. provided technical support. L.L. and X.X. gave relevant advice. I.R.-P., J.I. and Y.L. drew the schematic. J.L.
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