Targeting fibro-adipogenic progenitor cells in aging muscle: Exercise regulation and strategies to enhance regeneration and repair

The skeletal muscles are essential for locomotion and metabolic regulation. Muscle stem cells (SCs) are responsible for repair and regeneration in skeletal muscle; however, non-myogenic resident cell populations, including fibro-adipogenic progenitor (FAP) cells, play an important regulatory role in SCs. Loss of FAP function reduces muscle regeneration during aging. This results in impaired movement and metabolic dysfunctions. A central driver of the decline in SC and FAP function, at least in part, may be the loss of mitochondrial function with aging. These cellular and environmental changes from FAPs to SCs compromise muscle maintenance and regeneration in older adults, highlighting potential targets for strategies aimed at limiting age-related muscle degeneration. While the mechanism of FAP dysfunction with aging has not been fully characterized, this review highlights normal and aberrant FAP function in muscle regeneration after injury and identifies the potential role of aging-suppressed mitochondrial dysfunction in undermining FAP function and muscle homeostasis. This review also highlights clinical interventions that should be evaluated as potential strategies for improving FAP function, including various pharmacological treatments and exercise, as potential strategies to improve mitochondrial function and, therefore, improve FAP responses to injury and signaling crosstalk to SCs for muscle regeneration in aging or other muscle-wasting diseases.