Molecular indicators of denervation in aging human skeletal muscle

• Published in: Muscle & nerve 2019-10, Vol.60 (4), p.453-463
• Main Authors: Soendenbroe, Casper, Heisterberg, Mette F., Schjerling, Peter, Karlsen, Anders, Kjaer, Michael, Andersen, Jesper L., Mackey, Abigail L.
• Format: Article
• Language: English
• Subjects: acetylcholine receptor; Aged; Aged, 80 and over; Aging; Aging - genetics; Aging - metabolism; Cell adhesion; Cell adhesion & migration; Cell adhesion molecules; Denervation; Destabilization; Embryos; Fibers; Glucose; human muscle; Humans; Male; mRNA; Muscle Fibers, Skeletal - metabolism; Muscle, Skeletal - innervation; Muscle, Skeletal - metabolism; Muscles; Musculoskeletal system; Myosin; Myosin Heavy Chains - genetics; Myosin Heavy Chains - metabolism; neonatal myosin; Neonates; Neural cell adhesion molecule; Neural Cell Adhesion Molecules - genetics; Neural Cell Adhesion Molecules - metabolism; Newborn babies; Quadriceps Muscle - innervation; Quadriceps Muscle - metabolism; Receptors; Receptors, Cholinergic - genetics; Receptors, Nicotinic - genetics; Regeneration; Reinnervation; RNA, Messenger - metabolism; Sarcopenia; Skeletal muscle
• ISSN: 0148-639X; 1097-4598
• DOI: 10.1002/mus.26638

Introduction Muscle fiber denervation increases with age, yet studies at the tissue level are sparse due to the challenging nature of establishing the relative role of regeneration and denervation. Methods Muscle biopsies were obtained from the vastus lateralis of 70 healthy men (aged 72 ± 6 years; range, 65–94). Messenger RNA (mRNA) levels of acetylcholine receptors (AchR) were measured, and sections were stained for embryonic myosin, neonatal myosin (MHCn), and neural cell adhesion molecule (NCAM). Results Embryonic myosin+ fibers were rare, while MHCn+ and NCAM+ fibers were observed in all samples. Age (range, 65–94 years) was negatively associated with AchRγ mRNA. Discussion Muscle from healthy older individuals expressed developmental myosins to varying degrees but more than has been previously reported for young individuals. Along with the AchR correlations, we propose that these findings support the presence of neuromuscular junction destabilization, denervation, and reinnervation in aging human skeletal muscle.