Inflammatory, mitochondrial, and senescence-related markers: Underlying biological pathways of muscle aging and new therapeutic targets.

The maintenance of functional health is pivotal for achieving independent life in older age. The aged muscle is characterized by ultrastructural changes, including loss of type I and type II myofibers and a greater proportion of cytochrome c oxidase deficient and succinate dehydrogenase positive fibers. Both intrinsic (e.g., altered proteostasis, DNA damage, and mitochondrial dysfunction) and extrinsic factors (e.g., denervation, altered metabolic regulation, declines in satellite cells, and inflammation) contribute to muscle aging. Being a hub for several cellular activities, mitochondria are key to myocyte viability and mitochondrial dysfunction has been implicated in age-associated physical decline. The maintenance of functional organelles via mitochondrial quality control (MQC) processes is, therefore, crucial to skeletal myofiber viability and organismal health. The autophagy-lysosome pathway has emerged as a critical step of MQC in muscle by disposing organelles and proteins via their tagging for autophagosome incorporation and delivery to the lysosome for clearance. This pathway was found to be altered in muscle of physically inactive older adults. A relationship between this pathway and muscle tissue composition of the lower extremities as well as physical performance was also identified. Therefore, integrating muscle structure and myocyte quality control measures in the evaluation of muscle health may be a promising strategy for devising interventions fostering muscle health.