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

Neurobiol Aging. 2021 Aug:104:32-41. doi: 10.1016/j.neurobiolaging.2021.03.005. Epub 2021 Mar 12.

Abstract

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.

Keywords: Adeno-associated; Contractility; Follistatin; Motor unit number estimate; Myostatin; Neuromuscular junction; Sarcopenia; Single fiber electromyography; Tetanic; Twitch.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / pathology*
  • Aging / physiology*
  • Animals
  • Female
  • Follistatin / genetics
  • Follistatin / metabolism
  • Follistatin / pharmacology*
  • Gene Expression
  • Hypertrophy / genetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Muscle, Skeletal / pathology*
  • Neuromuscular Junction / drug effects*
  • Neuromuscular Junction / physiology*
  • Organ Size / drug effects
  • Organ Size / genetics
  • Sarcopenia / genetics
  • Sarcopenia / prevention & control
  • Synaptic Transmission / drug effects

Substances

  • Follistatin