Observational analysis reveals distinct aging phenotypes in muscle cells, highlighting roles of stem cells and microenvironments.
Skeletal muscle aging is a significant contributor to age-related frailty, sarcopenia, and metabolic disorders. To better understand human muscle aging, we profiled single cells and nuclei from the intercostal muscle of 17 adult donors, uncovering cellular changes across various muscle compartments. Our analysis identified distinct subsets of muscle stem cells with decreased ribosome biogenesis and increased CCL2 expression, leading to different aging phenotypes. The atlas also highlights the expansion of a novel myonuclei population, which may reflect compensatory re-innervation during aging. Additionally, we documented the role of the aging muscle microenvironment in attracting immune cells. To investigate muscle cell formation during development, we created the first human limb developmental atlas. Our data reveal two distinct rounds of myogenesis during human embryonic and early fetal development, each regulated by unique transcription factors. This combined research on muscle aging and development offers a comprehensive view of human muscle cell dynamics throughout the entire human lifespan.
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Hongbo Zhang (2025) studied this question.
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