Aging is associated with a progressive decline in skeletal muscle mass and function, contributing to reduced physical capacity in older adults. Central is the deterioration of satellite cells, our tissue-resident muscle stem cells, which participate in adaptation, repair, and regeneration of skeletal muscle. Evidence from in vitro, murine, and human studies indicates an age-related reduction in satellite cell content, notably within type II muscle fibers, alongside impairments in myogenic potential. There is no single causative mechanism behind satellite cell age-related dysfunction, but a convergence of morphological changes and intrinsic and extrinsic factors that affect satellite cell dynamics and its niche. Intrinsic factors such as signalling pathways, cellular senescence, impaired autophagy, mitochondrial dysfunction, and epigenetic modifications can impact satellite cell function. Concurrently, extrinsic factors can impact the satellite cell niche and their function such as systemic circulating factors and vasculature and extracellular matrix remodeling. These age-related alterations can diminish regenerative capacity, blunt hypertrophic responses, and impair recovery from disuse or injury. Satellite cell dysfunction is a pivotal contributor to age-related skeletal muscle decline, frailty, and the quality of life in older adults. Despite growing insights from in vitro and animal models, the key mechanistic changes that underlie human satellite cell dysfunction with age are not fully understood. Improved characterization of age-related satellite cell changes in humans is essential to preserving muscle health across the lifespan.
