Abstract
Motor unit remodelling involving repeated denervation and re-innervation occurs throughout life. The efficiency of this process declines with age contributing to neuromuscular deficits. This study investigated differentially expressed genes (DEG) in muscle following peroneal nerve crush to model motor unit remodelling in C57BL/6 J mice. Muscle RNA was isolated at 3 days post-crush, RNA libraries were generated using poly-A selection, sequenced and analysed using gene ontology and pathway tools. Three hundred thirty-four DEG were found in quiescent muscle from (26mnth) old compared with (4-6mnth) adult mice and these same DEG were present in muscle from adult mice following nerve crush. Peroneal crush induced 7133 DEG in muscles of adult and 699 DEG in muscles from old mice, although only one DEG (ZCCHC17) was found when directly comparing nerve-crushed muscles from old and adult mice. This analysis revealed key differences in muscle responses which may underlie the diminished ability of old mice to repair following nerve injury.
Highlights
Loss of skeletal muscle mass and function occurs over a substantial portion of later life and plays a crucial role in the development of frailty, leading to increased risk of falls, immobility, loss of independence and declining quality of life [68, 93, 112]
Adult control vs old control—which genes and pathways are differentially expressed in skeletal muscle from old compared with adult mice? A total of 334 differentially expressed genes (DEG) were found from a comparison of muscle from adult and old control mice; 199 of which were upregulated and 135 downregulated in muscles of old compared with adult mice (FDR > 0.05, Table 1)
The data obtained have identified DEG that occur in muscle with ageing, and show that all of the DEG found in muscle from old mice can be induced in adult mice by nerve crush
Summary
Loss of skeletal muscle mass and function occurs over a substantial portion of later life and plays a crucial role in the development of frailty, leading to increased risk of falls, immobility, loss of independence and declining quality of life [68, 93, 112]. In young and adult humans and animals, motor unit turnover occurs during everyday activities and is repaired by sprouting and regrowth of axons from the damaged nerve leading to rapid re-innervation of the muscle at the neuromuscular junctions (NMJs) [24]. This complex process involves coordinated responses by the damaged axon, terminal Schwann cells and denervated muscle fibre [52, 60].
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