Genetic rejuvenation of old muscle

Abstract

In advanced age, the stem cells responsible for muscle regeneration switch from reversible quiescence to irreversible senescence. Targeting a driver of senescence revives muscle stem cells and restores regeneration. See Article p.316 One of the properties crucial to the function of adult mammalian stem cells is the capacity to remain in a quiescent state for prolonged periods — and to respond when the need to regenerate arises. Loss of skeletal muscle mass and function are common features of advanced ageing in humans, associated with a loss of regenerative capacity of the skeletal muscle stem cells, known as satellite cells. Pura Munoz-Canoves and colleagues show that ageing satellite cells undergo an irreversible transition from quiescence to a pre-senescence state associated with increased expression of p16INK4a, a tumour-suppressor protein that has been identified as a marker for senescence. Repression of p16INK4a during adult life is shown to maintain satellite cells in a reversible quiescence state that allows muscle regeneration; p16INK4a is dysregulated in human geriatric satellite cells and the potential for muscle regeneration is lost.