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. 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. process characterized by alterations to cellular architecture leading to cell death. It is a tightly regulated process that prepares cells for removal by phagocytes, thereby enabling the elimination of damaged cells without undesirable immune responses. It is also referred to as programed cell death. a subfield of gerontology. It studies the aging process in an effort to understand why and how we age, and how to slow down aging. alterations in the chemical structure of DNA (such as a break in a strand of DNA, a base missing from the DNA backbone, or a chemically changed base) caused by endogenous and/or environmental agents. the age-associated loss of muscle strength. experimental procedure in which two living animals of different ages are joined surgically and develop a shared circulatory system. inducible type of autophagy (self-digestion of cellular components) responsible for the degradation of both long-lived soluble cellular proteins and complete organelles under stress conditions, such as starvation. A portion of the cytosol is surrounded by a de novo formed membrane (limiting membrane) that seals to generate a double-membrane organelle called an autophagosome. Fusion with lysosomes provides the enzymes required for degradation of the sequestered material. chemically reactive oxygen-containing molecules (including oxygen ions and peroxide) that are constantly produced in aerobic organisms as a by-product of oxygen metabolism. Uncontrolled increase in ROS production may result in a significant damage to cellular components and important signaling pathway alterations. the age-associated loss of muscle mass. It is estimated that humans over 50 years of age lose 0.5–1% muscle mass per year. skeletal muscle stem cells. They can proliferate, differentiate, and fuse into myofibers, and also self-renew to make more satellite cells. cellular state of irreversible cell cycle arrest induced by damage or stress. Senescent cells secrete a set of cytokines, growth factors, and proteases, usually referred to as the senescent-associated secretory phenotype (SASP).