Muscle recovery following a disuse event is impaired in many older adults which could increase the risk for falls, fractures and disability. We have shown that muscle macrophages are dysregulated during the regrowth period following a disuse event in aged muscle. Therefore, we have proposed a series of elegant, pre-clinical mouse experiments to determine the effectiveness of various immunomodulating therapeutics and identify specific mechanisms underlying age-related muscle immune dysregulation in skeletal muscle during regrowth from disuse. We will utilize state-of-the-art approaches to phenotype muscle macrophages (FACS, single cell RNA sequencing, immunofluorescence) coupled with mouse genetics and bone transfer experiments to extensively address these questions. The data generated will be the first of its kind identifying the mechanisms underlying macrophage dysregulation in aged muscle during regrowth following disuse atrophy while also testing if immunomodulation amplifies muscle and functional recovery in the old.
A high priority in the face of a rapidly growing aging population is a need to further understand the cellular mechanisms behind impaired muscle regrowth following disuse with aging. In this proposal, we will test macrophage-specific therapies and identify specific mechanisms underlying impaired muscle regrowth. These data will be foundational in the development of new immunotherapies to enhance muscle recovery in older adults following disuse events (e.g., surgery).
