Muscle stem cell aging: regulation and rejuvenation

•Skeletal muscle regenerative capacity declines with aging.•Muscle stem cell number and function decline with aging.•Muscle stem cell aging is caused by both extrinsic and intrinsic alterations.•Old muscle stem cells can be rejuvenated by youthful environmental factors.•Interference with age-associated intrinsic changes can rejuvenate stem cells.

Aging is characterized by a progressive decline of physiological integrity leading to the loss of tissue function and vulnerability to disease, but its causes remain poorly understood. Skeletal muscle has an outstanding regenerative capacity that relies on its resident stem cells (satellite cells). This capacity declines with aging, and recent discoveries have redefined our view of why this occurs. Here, we discuss how an interconnection of extrinsic changes in the systemic and local environment and cell-intrinsic mechanisms might provoke failure of normal muscle stem cell functions with aging. We focus particularly on the emergent biology of rejuvenation of old satellite cells, including cells of geriatric age, by restoring traits of youthfulness, with the final goal of improving human health during aging.