Older adults are prone to experience periods of muscle disuse resulting in muscle atrophy and weakness. Moreover, muscle recovery following a disuse event is impaired in older adults. Therefore, 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 with aging. Macrophages and other immune cell populations (e.g., T-cells) are of critical importance to optimally restore muscle size following a period of disuse, however, their role under such conditions in aging skeletal muscle has surprisingly not been elucidated. Therefore, using a well-established mouse model of muscle disuse and regrowth, we have produced compelling preliminary data demonstrating impaired muscle regrowth in aged mice and this is accompanied by an altered macrophage immune response and recruitment in skeletal muscle during recovery. In the current proposal, we have proposed to conduct an extensive time course of the muscle macrophage (and other immune cells) response in old and young mice during recovery from disuse. We will also determine if inhibiting macrophage recruitment in young mice will result in a phenotype characteristic of old mice during recovery from disuse. We will utilize combined unique approaches of FACS and single cell RNA sequencing to extensively address these questions. These data will be foundational for additional mechanistic studies investigating upstream mediators of macrophage and other immune cell responses during recovery from disuse while also using novel immunotherapies to optimize muscle recovery in older muscle.
Impaired muscle recovery following disuse events (e.g. illness, injury) represents a significant health problem for the aging adult as this can lead to a downward cycle of weakness, falls and loss of independence. This proposal seeks to investigate muscle macrophages and other immune cell populations as a mechanism behind the impaired muscle regrowth in aging following disuse. These data will be foundational in the development of new immunotherapies to enhance muscle recovery from disuse.
