Aging of Muscle Stem Cells

Skeletal Muscle has a remarkable adaptive and regenerative capacity, which is primarily due to the actions of the muscle-resident stem cell population. Aging is associated with a progressive loss in tissue function, which is associated with a decline in muscle stem cell function and total muscle stem cell pool size. Whether or not the loss in muscle stem cell function is instrumental to the progression of age-related muscle wasting (termed sarcopenia) is somewhat controversial. However, the evidence suggests that muscle stem cell dysfunction is directly related to the loss of normal muscle regeneration and response to normal physiological stimuli, which eventually leads to the loss of functional skeletal muscle. Muscle stem cell dysfunction is multifactorial and the result of alterations in local and systemic factors that we describe as niche-related or extrinsic factors and alterations in cell signaling and cell metabolic processes, which we describe as intrinsic factors. It is the combination of intrinsic and extrinsic factors that dictate the level of muscle stem cell dysfunction. Although at present it appears that the eventual decline in muscle stem cell function is inevitable, studies employing resistance exercise training regimes have shown an enhancement of the satellite cell pool which may mitigate or delay the decline in muscle aging. Both intrinsic and extrinsic factors must be considered in the design of novel therapeutic strategies to ensure successful and efficacious treatment of sarcopenia which is an important cause of morbidity and mortality and imposes a significant strain on the health-care system.