Profiling age-related muscle weakness and wasting: neuromuscular junction transmission as a driver of age-related physical decline

Padilla, Carlos J.; Harrigan, Markus E.; Harris, Hallie; Schwab, Jan M.; Rutkove, Seward B.; Rich, Mark M.; Clark, Brian C.; Arnold, W. David

doi:10.1007/s11357-021-00369-3

Cited by 39 publications

(32 citation statements)

References 87 publications

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“…Briefly, NMJ transmission refers to the release of acetylcholine (ACh) from the motoneuron and binding to the synaptic region of the muscle fibre to initiate a muscle fibre action potential and contraction. Aged rats have demonstrated a decline in NMJ transmission stability and reliability which correlated with declines in functional measures such as grip strength (Padilla et al., 2021), and voluntary running exercise improved NMJ transmission stability in older mice (Chugh et al., 2021). However, these beneficial effects of exercise on NMJ transmission are less clear in older age (Deschenes et al., 2011).…”

Section: Introductionmentioning

confidence: 99%

Ageing and exercise‐induced motor unit remodelling

Jones

Chiou

Atherton

et al. 2022

The Journal of Physiology

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Section: Introductionmentioning

confidence: 99%

Ageing and exercise‐induced motor unit remodelling

Jones

Chiou

Atherton

et al. 2022

The Journal of Physiology

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“…Interestingly, the severe unloading-induced decrement in maximal force production was roughly the same whether muscle contraction was elicited by stimulating nerve terminal endings, or the sarcolemma. This made it difficult initially to attribute loss of strength specifically to either neural or myofiber impairment; both have been shown to negatively impact contractile force ( Deschenes et al, 2017 ; Monti et al, 2021 ; Padilla et al, 2021 ). With little doubt, the difference in loss of peak force following unloading cannot be explained by differential adaptations in muscle size as results showed that adult and juvenile muscles experienced similar atrophy with unloading.…”

Section: Discussionmentioning

confidence: 99%

Juvenile Neuromuscular Systems Show Amplified Disturbance to Muscle Unloading

et al. 2021

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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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“…Several lines of evidence suggest that age-related changes in the NMJ play a key role in musculoskeletal impairment with aging [ 15 , 16 , 56 , 79 , 80 , 86 , 87 , 88 ]. Indeed there is increasing consensus that functional muscle denervation is a principal factor leading to sarcopenia [ 56 , 89 ], and some even describe sarcopenia primarily as a “disorder of the NMJ” [ 80 ]. Despite the continuing ambiguity of sarcopenia etiology, it is clear that, at a minimum, age-dependent changes in the peripheral nerve and NMJ contribute to the muscle pathology in sarcopenia [ 16 , 56 , 81 , 84 ].…”

Section: The Nmj In Aging Musclementioning

confidence: 99%

The Neuromuscular Junction: Roles in Aging and Neuromuscular Disease

Iyer

Shah

Lovering

2021

IJMS

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The neuromuscular junction (NMJ) is a specialized synapse that bridges the motor neuron and the skeletal muscle fiber and is crucial for conversion of electrical impulses originating in the motor neuron to action potentials in the muscle fiber. The consideration of contributing factors to skeletal muscle injury, muscular dystrophy and sarcopenia cannot be restricted only to processes intrinsic to the muscle, as data show that these conditions incur denervation-like findings, such as fragmented NMJ morphology and corresponding functional changes in neuromuscular transmission. Primary defects in the NMJ also influence functional loss in motor neuron disease, congenital myasthenic syndromes and myasthenia gravis, resulting in skeletal muscle weakness and heightened fatigue. Such findings underscore the role that the NMJ plays in neuromuscular performance. Regardless of cause or effect, functional denervation is now an accepted consequence of sarcopenia and muscle disease. In this short review, we provide an overview of the pathologic etiology, symptoms, and therapeutic strategies related to the NMJ. In particular, we examine the role of the NMJ as a disease modifier and a potential therapeutic target in neuromuscular injury and disease.

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Profiling age-related muscle weakness and wasting: neuromuscular junction transmission as a driver of age-related physical decline

Cited by 39 publications

References 87 publications

Ageing and exercise‐induced motor unit remodelling

Ageing and exercise‐induced motor unit remodelling

Juvenile Neuromuscular Systems Show Amplified Disturbance to Muscle Unloading

The Neuromuscular Junction: Roles in Aging and Neuromuscular Disease

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