The immune landscape of murine skeletal muscle regeneration and aging.
Abstract
Age-related alterations in the immune system are starting to emerge as key contributors to impairments found in aged organs. A decline in regenerative capacity is a hallmark of tissue aging; however, the contribution of immune aging to regenerative failure is just starting to be explored. Here, we apply a strategy combining single-cell RNA sequencing with flow cytometry, histological analysis, and functional assays to perform a complete analysis of the immune environment of the aged regenerating skeletal muscle on a time course following injury with single-cell resolution. Our results reveal an unanticipated complexity and functional heterogeneity in immune populations within the skeletal muscle that have been regarded as homogeneous. Furthermore, we uncover a profound remodeling of both myeloid and lymphoid compartments in aging. These discoveries challenge established notions on immune regulation of skeletal muscle regeneration, providing a set of potential targets to improve skeletal muscle health and regenerative capacity in aging.
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Research summary
The paper explores the immune landscape in the context of skeletal muscle regeneration and aging, addressing the role of immune aging in regenerative failure. This aligns with longevity research as it investigates underlying mechanisms that contribute to age-related decline in tissue regeneration. However, while the findings are solid and provide insights into immune regulation, they represent an incremental advance rather than a major breakthrough, limiting their overall impact on the field.
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