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

NEUROBIOLOGY OF AGING

卷:104

Article

Iyer, Chitra C.¹  Chugh, Deepti¹  Bobbili, Prameela J.¹  Blatnik, Anton J., III²  Crum, Alexander E.¹  Yi, Allen F.³  Kaspar, Brian K.⁴  Meyer, Kathrin C.^4,5  Burghes, Arthur H. M.²  Arnold, W. David^1,6,7,8 

[1] Ohio State Univ, Dept Neurol, Wexner Med Ctr, Neuromuscular Div, 395 W 12th Ave, Columbus, OH 43210 USA

[2] Ohio State Univ, Wexner Med Ctr, Dept Biol Chem & Pharmacol, Columbus, OH 43210 USA

[3] Ohio State Univ, Coll Med, Columbus, OH 43210 USA

[4] Nationwide Childrens Hosp, Res Inst, Columbus, OH USA

[5] Ohio State Univ, Dept Pediat, Columbus, OH 43210 USA

[6] Ohio State Univ, Wexner Med Ctr, Dept Phys Med & Rehabil, Columbus, OH 43210 USA

[7] Ohio State Univ, Wexner Med Ctr, Dept Neurosci, Columbus, OH 43210 USA

[8] Ohio State Univ, Wexner Med Ctr, Dept Physiol & Cell Biol, Columbus, OH 43210 USA

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

DOI  :  10.1016/j.neurobiolaging.2021.03.005

来源: Elsevier

【 摘 要 】

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. (c) 2021 Elsevier Inc. All rights reserved.

【 授权许可】

Free