TY - JOUR

T1 - Muscle-nerve communication and the molecular assessment of human skeletal muscle denervation with aging

AU - Søndenbroe, Casper

AU - Andersen, Jesper L

AU - Mackey, Abigail L

PY - 2021

Y1 - 2021

N2 - Muscle fiber denervation is a major contributor to the decline in physical function observed with aging. Denervation can occur through breakdown of the NMJ itself, affecting only that particular fiber, or through the death of a motoneuron, which can lead to a loss of all the muscle fibers in that motor unit. In this review we discuss the muscle-nerve relationship, where signaling from both the motor neuron and the muscle fiber is required for maximal preservation of neuromuscular function in old age. Physical activity is likely to be the most important single factor that can contribute to this preservation. Furthermore, we propose that inactivity is not an innocent bystander, but plays an active role in denervation through the production of signals hostile to neuron survival. Investigating denervation in human muscle tissue samples is challenging due to the shared protein profile of regenerating and denervated muscle fibers. In this review we provide a detailed overview of the key traits observed in immunohistochemical preparations of muscle biopsies from healthy young and elderly individuals. Overall, a combination of assessing tissue samples, circulating biomarkers, and electrophysiological assessments in humans will prove fruitful in the quest to gain more understanding of denervation of skeletal muscle. In addition, cell culture models represent a valuable tool in the search for key signaling factors exchanged between muscle and nerve, and which exercise has the capacity to alter.

AB - Muscle fiber denervation is a major contributor to the decline in physical function observed with aging. Denervation can occur through breakdown of the NMJ itself, affecting only that particular fiber, or through the death of a motoneuron, which can lead to a loss of all the muscle fibers in that motor unit. In this review we discuss the muscle-nerve relationship, where signaling from both the motor neuron and the muscle fiber is required for maximal preservation of neuromuscular function in old age. Physical activity is likely to be the most important single factor that can contribute to this preservation. Furthermore, we propose that inactivity is not an innocent bystander, but plays an active role in denervation through the production of signals hostile to neuron survival. Investigating denervation in human muscle tissue samples is challenging due to the shared protein profile of regenerating and denervated muscle fibers. In this review we provide a detailed overview of the key traits observed in immunohistochemical preparations of muscle biopsies from healthy young and elderly individuals. Overall, a combination of assessing tissue samples, circulating biomarkers, and electrophysiological assessments in humans will prove fruitful in the quest to gain more understanding of denervation of skeletal muscle. In addition, cell culture models represent a valuable tool in the search for key signaling factors exchanged between muscle and nerve, and which exercise has the capacity to alter.

U2 - 10.1152/ajpcell.00174.2021

DO - 10.1152/ajpcell.00174.2021

M3 - Journal article

C2 - 34161153

VL - 321

SP - C317-C329

JO - American Journal of Physiology: Cell Physiology

JF - American Journal of Physiology: Cell Physiology

SN - 0363-6143

IS - 2

ER -