Adaptive Remodeling of the Neuromuscular Junction with Aging

Abstract

Aging is associated with gradual degeneration, in mass and function, of the neuromuscular system. This process, referred to as "sarcopenia", is considered a disease by itself, and it has been linked to a number of other serious maladies such as type II diabetes, osteoporosis, arthritis, cardiovascular disease, and even dementia. While the molecular causes of sarcopenia remain to be fully elucidated, recent findings have implicated the neuromuscular junction (NMJ) as being an important locus in the development and progression of that malady. This synapse, which connects motor neurons to the muscle fibers that they innervate, has been found to degenerate with age, contributing both to senescent-related declines in muscle mass and function. The NMJ also shows plasticity in response to a number of neuromuscular diseases such as amyotrophic lateral sclerosis (ALS) and Lambert-Eaton myasthenic syndrome (LEMS). Here, the structural and functional degradation of the NMJ associated with aging and disease is described, along with the measures that might be taken to effectively mitigate, if not fully prevent, that degeneration.

Keywords: NMJ; acetylcholine (ACh); endplate; nerve terminal; sarcopenia; vesicle.

Figure 1

Positioning of the peri-synaptic Schwann cell at the neuromuscular junction.

Figure 2

Illustration of the pre- and postsynaptic features of the NMJ; red circles indicate the presence of ligand-gated acetylcholine receptors at the crests of postsynaptic junctional folds, and voltage-gated sodium channels in the depths of those folds.

Figure 3

Micrograph showing close coupling of presynaptic vesicles and terminal branches with postsynaptic receptors. Presynaptic terminal branches are stained green, presynaptic vesicles are stained blue and postsynaptic receptors are stained red. Note the greater complexity of nerve terminal branching in aged NMJ.

Figure 4

Illustration of aged and young adult endplates. Note more shallow gutters in the aged neuromuscular junction, with fewer receptors.

Figure 5

NCAM expression of aged (22 mo) and young adult (8 mo) muscle fibers under either control or unweighted (hindlimb suspended) conditions. Note that the NCAM expression is greatest in aged, unweighted fibers. Source: Deschenes and Wilson (2003).

Figure 6

Synthesis of ACh by choline acetyltransferase at the presynaptic terminal.