Follistatin-induced muscle hypertrophy in aged mice improves neuromuscular junction innervation and function.

• Follistatin overexpression was studied in aged mice between 24 to 27 months of age. • Follistatin increased muscle size and absolute torque production in aged mice. • Normalized twitch torque, but not tetanic torque, was reduced with follistatin. • Follistatin improved neuromuscular junction transmission but not motor unit loss. • Endogenous mouse follistatin but not myostatin was increased in aged mice. Sarcopenia, or age-related loss of muscle mass and strength, is an important contributor to loss of physical function in older adults. The pathogenesis of sarcopenia is likely multifactorial, but recently the role of neurological degeneration, such as motor unit loss, has received increased attention. Here, we investigated the longitudinal effects of muscle hypertrophy (via overexpression of human follistatin, a myostatin antagonist) on neuromuscular integrity in C57BL/6J mice between the ages of 24 and 27 months. Following follistatin overexpression (delivered via self-complementary adeno-associated virus subtype 9 injection), muscle weight and torque production were significantly improved. Follistatin treatment resulted in improvements of neuromuscular junction innervation and transmission but had no impact on age-related losses of motor units. These studies demonstrate that follistatin overexpression-induced muscle hypertrophy not only increased muscle weight and torque production but also countered age-related degeneration at the neuromuscular junction in mice. [ABSTRACT FROM AUTHOR]