Intrinsic and extrinsic factors in muscle aging

The regenerative potential of skeletal muscle, and overall muscle mass, decline with age. This regenerative potential may be influenced by autocrine growth factors intrinsic to the muscle itself. Extrinsic host factors that may influence muscle regeneration include hormones, growth factors secreted in a paracrine manner by accessory cells, innervation, and antioxidant mechanisms. Unaccustomed exercise, which involves mechanical overload of myofibers, provides a convenient method for studying muscle regeneration in both humans and animal models. An inflammatory response ensues in which distinctive populations of macrophages infiltrate the affected tissue: some of these macrophages are involved in phagocytosis of damaged fibers; other macrophages arriving at later times may deliver growth factors or cytokines that promote regeneration. These include fibroblast growth factor and insulin-like growth factor, which are important regulators of muscle precursor cell growth and differentiation, as well as nerve growth factor, which is essential for maintenance or reestablishment of neuronal contact. Other cytokines, including interleukin-1, tumor necrosis factor, interleukin-15, and ciliary neurotrophic factor, have a strong influence on the balance between muscle protein synthesis and breakdown. The functional activity of invading macrophages can be influenced by age, by factors in myofibers and extracellular matrix, and can be influenced systemically by the antioxidant status of the host.