Skeletal muscle cells develop from a mesodermal cell population called myoblasts. These spindle-shaped cells divide and fuse to form long, multinucleated tubes, called myotubes, that differentiate into muscle fibers.
During this period, many contractile proteins appear, some of which exist in embryonic isoforms. By the seventh week of gestation, distinct muscle and tendinous structures can be identified. Further steps in muscle differentiation include the production of structural and metabolic proteins, organization of the ECM, and innervation.
Classic developmental studies demonstrate that the formation of neuromuscular junctions is a mutually inductive event; neurons induce postsynaptic differentiation in myofibers, and myofibers induce presynaptic differentiation in motor axon terminals. More recent experiments indicate that Schwann cells, which also surround axon terminals, play an active role in the formation and maintenance of the neuromuscular junction.
In childhood, both muscle fibers and tendons increase in length. The region of the myotendinous junction appears to be the site at which these fibers lengthen, rather than near the muscle belly.6 Sarcomeres remain constant in size; additional units are added to the fiber during growth. In adulthood, the primary mechanism by which the musculotendinous unit lengthens is elongation of the muscle belly.
During aging, there is loss of muscle mass and strength, termed sarcopenia. It is per- haps, unfortunately, a universal process. The mechanisms are complex, with both myogenic and neural components.7 It appears that regeneration of muscle fibers in older individuals proceeds more slowly, a result of biochemical, hormonal, and cytokine- related changes. Aging may also express its effects via the relative loss of testosterone, which occurs with advancing age. Testosterone increases protein synthesis in muscle and decreases its breakdown.