The immune landscape of murine skeletal muscle regeneration and aging
Neuza S. Sousa, Marta Bica, Margarida F. Brás, Ana Catarina Sousa, Inês B. Antunes, Isabel A. Encarnação, Tiago Costa, Inês B. Martins, Nuno L. Barbosa‐Morais, Pedro Sousa‐Victor, Joana Neves
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.