Skeletal muscle cell aging and stem cells

Skeletal muscle tissue-resident muscle stem cells, also called satellite cells, can undergo self-renewal and differentiation via adult myogenesis to generate muscle lineage through adult life. Satellite cells remain dormant in the quiescent state until the muscle suffers an injury. Upon damage to the muscle, the dormant satellite cells are activated, resulting in myogenesis mediated by its microenvironment. There is a progressive decline in the regenerative capacity of the muscles due to age-related impairment. Aging is negatively associated with satellite cell integrity because it loses its muscle cell microenvironment support during aging, which leads to cellular damage and results in impaired myogenesis and the accumulation of unrepaired muscle cells in aging tissue. About 40% of the human body mass is comprised of skeletal muscle, which indicates that the satellite cells contribute significantly to the total number of cells in humans. Hence, impaired satellite cell function due to the dysregulation of transcriptional and epigenetic activator effectors will have a major impact on the overall aging in humans because of the altered activities of extrinsic and intrinsic factors during muscle cell aging. However, results from studies regarding aged satellite cell function in a mimicked young environment are contentious, as interactive signaling pathways associated with both extrinsic and intrinsic factors are altered during aging. Therefore, a comprehensive understanding of all the extrinsic and intrinsic factors or mechanisms/pathways that are altered during muscle cell aging is required to enhance our knowledge on aging and develop potential novel therapeutics to slow the effects of aging. In this chapter, we focus our discussion on skeletal muscle and its satellite cell function, and the role played by extrinsic and intrinsic factors in the regulation of their gene expression, metabolism, signaling pathway or epigenetics, and their altered regulations during aging.