Age‐related changes in the structure and function of mammalian neuromuscular junctions

Abstract

As mammals age, their neuromuscular junctions (NMJs) change their form, with an increasingly complex system of axonal branches innervating increasingly fragmented regions of postsynaptic differentiation. It has been suggested that this remodeling is associated with impairment of neuromuscular transmission and that this contributes to age-related muscle weakness in mammals, including humans. Here, we review previous work on NMJ aging, most of which has focused on either structure or function, as well as a new study aimed at seeking correlation between the structure and function of individual NMJs. While it is clear that extensive structural changes occur as part of the aging process, it is much less certain how, if at all, these are correlated with an impairment of function. This leaves open the question of whether loss of NMJ function is a significant cause of age-related muscle weakness.

A new protein curbs the hypertrophic effect of myostatin inhibition, adding remarkable endurance to motor performance in mice

“…We are planning further studies to investigate reporter genes that are up-or down-regulated after administration of our compounds as the first step toward entangling the putative interferences among these multiple pathways. In parallel, to confirm the pivotal role of NMJs in improving endurance, we plan to investigate if the same increment of enduring motor performance can also be observed in aged mice, where weakening and fragmentation of the NMJ is known to occur [38]. Fc-nLG3 (A, right panel).…”

NMJ maintenance and repair in aging

“…Several general conclusions can be drawn from these studies. 1) NMJs acquire deleterious morphological, functional, and molecular features with advancing age, and ultimately degenerate [9–12]. 2) While NMJs acquire age-related features, the underlying cause of such changes remains debated.…”

NMJ-Analyser: high-throughput morphological screening of neuromuscular junctions identifies subtle changes in mouse neuromuscular disease models

“…We found structural changes in the nerve terminal and the pre-and post-synaptic interaction (for example, 'compactness') in both strains, before denervation could be detected by manual analysis, highlighting a major strength of NMJ-Analyser. These results suggest an initial change in neuromuscular morphology, known as remodelling, a process involving the terminal Schwann cells that precedes NMJ dismantling 2,4,5,67,68,70 .…”

“…In health, NMJs are dynamic structures with constant remodelling, and continuous innervation/denervation 1,2 . A permanent morphological change in the NMJ may precede an irreversible denervation process, thought to be the earliest sign of degeneration in multiple human neuromuscular disorders, as well as part of the natural aging process [3][4][5][6][7][8][9][10][11][12] .…”

“…Results 'NMJ-Analyser' for comprehensive and systematic assessment of NMJs in mice. NMJs are dynamic structures with specific age-related morphological features throughout life 1,4,[43][44][45] . The morphology of mouse NMJs transitions from poly-innervated (immature, <1-month old mice), mono-innervated (mature, 1 to 18-month old mice) to fragmented/degenerated in aging mice (≥18-month old mice) 43,45,46 .…”