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.
The neuromuscular system accounts for a large portion (~40%) of whole body mass while enabling body movement, including physical work and exercise. At the core of this system is the neuromuscular junction (NMJ) which is the vital synapse transducing electrical impulses from the motor neurons to their post-synaptic myofibers. Recent findings suggest that subcellular features (active zones) of the NMJ are distinctly sensitive to changes in activity relative to cellular features (nerve terminal branches, vesicles, receptors) of the NMJ. In the present investigation, muscles with different recruitment patterns, functions, and myofiber type profiles (soleus, plantaris, extensor digitorum longus [EDL]) were studied to quantify both cellular and subcellular NMJ characteristics along with myofiber type profiles. Results indicated that, in general, dimensions of subcellular components of NMJs mirrored cellular NMJ features when examining inter-muscle NMJ architecture. Typically, it was noted that the NMJs of the soleus, with its most pronounced recruitment pattern, were larger (p < 0.05) than NMJs of less recruited muscles. Moreover, it was revealed that myofiber size did not dictate NMJ size as soleus muscles displayed the smallest fibers (p < 0.05) while the plantaris muscles exhibited the largest fibers. In total, these data show that activity determines the size of NMJs and that generally, size dimensions of cellular and subcellular components of the NMJ are matched, and that the size of NMJs and their underlying myofibers are uncoupled.
Muscle unloading results in severe disturbance in neuromuscular function. During juvenile stages of natural development, the neuromuscular system experiences a high degree of plasticity in function and structure. This study aimed to determine whether muscle unloading imposed during juvenile development would elicit more severe disruption in neuromuscular function than when imposed on fully developed, mature neuromuscular systems. Twenty juvenile (3 months old) and 20 mature (8 months old) rats were equally divided into unloaded and control groups yielding a total of four groups (N = 10/each). Following the 2 week intervention period, soleus muscles were surgically extracted and using an ex vivo muscle stimulation and recording system, were examined for neuromuscular function. The unloading protocol was found to have elicited significant (P ≤ 0.05) declines in whole muscle wet weight in both juvenile and mature muscles, but of a similar degree (P = 0.286). Results also showed that juvenile muscles displayed significantly greater decay in peak force due to unloading than mature muscles, such a finding was also made for specific tension or force/muscle mass. When examining neuromuscular efficiency, i.e., function of the neuromuscular junction, it again was noted that juvenile systems were more negatively affected by muscle unloading than mature systems. These results indicate that juvenile neuromuscular systems are more sensitive to the effects of unloading than mature ones, and that the primary locus of this developmental related difference is likely the neuromuscular junction as indicated by age-related differences in neuromuscular transmission efficiency.
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