Transcriptomic analysis of skeletal muscle regeneration across mouse lifespan identifies altered stem cell states.
Abstract
In aging, skeletal muscle regeneration declines due to alterations in both myogenic and non-myogenic cells and their interactions. This regenerative dysfunction is not understood comprehensively or with high spatiotemporal resolution. We collected an integrated atlas of 273,923 single-cell transcriptomes and high-resolution spatial transcriptomic maps from muscles of young, old and geriatric mice (~5, 20 and 26 months old) at multiple time points following myotoxin injury. We identified eight immune cell types that displayed accelerated or delayed dynamics by age. We observed muscle stem cell states and trajectories specific to old and geriatric muscles and evaluated their association with senescence by scoring experimentally derived and curated gene signatures in both single-cell and spatial transcriptomic data. This revealed an elevation of senescent-like muscle stem cell subsets within injury zones uniquely in aged muscles. This Resource provides a holistic portrait of the altered cellular states underlying muscle regenerative decline across mouse lifespan.
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Research summary
The paper addresses the decline in skeletal muscle regeneration with age, focusing on the underlying cellular mechanisms and alterations in stem cell states. This is directly relevant to understanding the biological processes of aging and potential interventions to improve regenerative capacity, which aligns with longevity research. The findings contribute important insights into the cellular dynamics of muscle regeneration across the lifespan, making it a significant advance in the field, though not groundbreaking enough to warrant a higher impact score.
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