Table 1.
Effect of aging on key neuromuscular junction (NMJ) mediators and the possible outcomes in the NMJ that may contribute to sarcopenia
| Mediator | Effect of aging | Possible outcomes in NMJ | References |
|---|---|---|---|
| Presynaptic signaling | |||
| P/Q-type VGCC | ↓ | • ↓ P/Q-type VGCC activity | [48] |
| • ↓ Calcium influx | |||
| Bassoon | ↓ | • ↓ Signal transmission | [40, 42, 48] |
| • ↓ Muscle contraction | |||
| ACh | ↑ | • NMJ fragmentation | [58] |
| • Denervation | |||
| • Axon sprouting | |||
| Agrin | ↑ | • NMJ fragmentation | [77] |
| • Nerve terminal branching | |||
| • Denervation | |||
| • Smaller AChRs clusters | |||
| LRP4 | ↓ | • ↓ Agrin-LRP4-MuSK signaling | [68] |
| p-MuSK | ↓ | ||
| BDNF (serum) | ↓ | • Denervation (?) | [89–91] |
| • ↓ ACh release (?) | |||
| • ↓ Synapse maintenance (?) | |||
| BDNF (mRNA) | = | • ——————— | [67] |
| GDNF (mRNA) | ↓ | • ↓ ACh release (?) | [95] |
| GDNF | =/↓ | • ↓ Postsynaptic maintenance (?) | |
| Postsynaptic signaling | |||
| CGRP | ↑ | • ↓ Reinnervation (?) | [77] |
| GAP-43 | ↑ | [77, 113] | |
ACh, acetylcholine; AChRs, acetylcholine receptors; BDNF, brain-derived neurotrophic factor; CGRP, calcitonin gene–related protein; GAP-43, growth-associated protein; GDNF, glial-cell-line-derived neurotrophic factor; LRP4, low-density lipoprotein receptor–related protein 4; p-MuSK, phosphorylated muscle-specific kinase; VGCC, voltage-gated calcium channel