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The Neuromuscular Junction: Aging at the Crossroad between Nerves and Muscle.

Gonzalez-Freire M, de Cabo R, Studenski SA, Ferrucci L - Front Aging Neurosci (2014)

Bottom Line: Aging is associated with a progressive loss of muscle mass and strength and a decline in neurophysiological functions.However, whether changes in the NMJ precede or follow the decline of muscle mass and strength remains unresolved.Many factors such as mitochondrial dysfunction, oxidative stress, inflammation, changes in the innervation of muscle fibers, and mechanical properties of the motor units probably perform an important role in NMJ degeneration and muscle mass and strength decline in late life.

View Article: PubMed Central - PubMed

Affiliation: Translational Gerontology Branch, National Institute on Aging, Intramural Research Program, National Institutes of Health , Baltimore, MD , USA ; Longitudinal Studies Section, Baltimore Longitudinal Study of Aging, National Institute on Aging, National Institutes of Health , Baltimore, MD , USA.

ABSTRACT
Aging is associated with a progressive loss of muscle mass and strength and a decline in neurophysiological functions. Age-related neuromuscular junction (NMJ) plays a key role in musculoskeletal impairment that occurs with aging. However, whether changes in the NMJ precede or follow the decline of muscle mass and strength remains unresolved. Many factors such as mitochondrial dysfunction, oxidative stress, inflammation, changes in the innervation of muscle fibers, and mechanical properties of the motor units probably perform an important role in NMJ degeneration and muscle mass and strength decline in late life. This review addresses the primary events that might lead to NMJ dysfunction with aging, including studies on biomarkers, signaling pathways, and animal models. Interventions such as caloric restriction and exercise may positively affect the NMJ through this mechanism and attenuate the age-related progressive impairment in motor function.

No MeSH data available.


Related in: MedlinePlus

The architecture of a neuromuscular junction (NMJ). (A, B) The NMJ is composed of three elements: pre-synaptic (motor nerve terminal), intrasynaptic (synaptic basal lamina), and post-synaptic component (muscle fiber and muscle membrane) (Punga and Ruegg, 2012). When the action potential reaches the motor nerve terminal the calcium channels open and the calcium enters in the neuron and delivers ACh in the synaptic cleft. (C) AChR activates the DHPRs located in the sarcolemma and by induction the RyRs. Calcium released from the sarcoplasmic reticulum through the RyRs binds to troponin C and allows cross-bridge cycling and force production.
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Figure 1: The architecture of a neuromuscular junction (NMJ). (A, B) The NMJ is composed of three elements: pre-synaptic (motor nerve terminal), intrasynaptic (synaptic basal lamina), and post-synaptic component (muscle fiber and muscle membrane) (Punga and Ruegg, 2012). When the action potential reaches the motor nerve terminal the calcium channels open and the calcium enters in the neuron and delivers ACh in the synaptic cleft. (C) AChR activates the DHPRs located in the sarcolemma and by induction the RyRs. Calcium released from the sarcoplasmic reticulum through the RyRs binds to troponin C and allows cross-bridge cycling and force production.

Mentions: The reason for a progressive impairment of the re-innervation process with aging is unknown, but some lines of evidence point to changes that occur with aging in the neuromuscular junction (NMJ), which is the synaptic interface between a branch of a motor neuron and muscle cells. The NMJ is composed of three elements: pre-synaptic (motor nerve terminal), intrasynaptic (synaptic basal lamina), and post-synaptic part (muscle fiber and muscle membrane) (Punga and Ruegg, 2012). When an action potential reaches the pre-synaptic element, voltage-dependent calcium channels open allowing calcium to enter the neuron and trigger the delivery of acetylcholine (ACh) in the synaptic cleft. Acetylcholine triggers nicotin acetylcholine receptors (nAChR) located in the post-synaptic membrane to produce an action potential, which in turn, activates voltage-gated dihydropyridine receptors (DHPRs) located in the sarcolemma and by induction, ryanodine receptors (RyRs). Of note, the post-synaptic membrane presents folds that expand its area. Calcium released from the sarcoplasmic reticulum through the RyRs binds to troponin C and allows cross-bridge cycling and force production (Figure 1).


The Neuromuscular Junction: Aging at the Crossroad between Nerves and Muscle.

Gonzalez-Freire M, de Cabo R, Studenski SA, Ferrucci L - Front Aging Neurosci (2014)

The architecture of a neuromuscular junction (NMJ). (A, B) The NMJ is composed of three elements: pre-synaptic (motor nerve terminal), intrasynaptic (synaptic basal lamina), and post-synaptic component (muscle fiber and muscle membrane) (Punga and Ruegg, 2012). When the action potential reaches the motor nerve terminal the calcium channels open and the calcium enters in the neuron and delivers ACh in the synaptic cleft. (C) AChR activates the DHPRs located in the sarcolemma and by induction the RyRs. Calcium released from the sarcoplasmic reticulum through the RyRs binds to troponin C and allows cross-bridge cycling and force production.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4127816&req=5

Figure 1: The architecture of a neuromuscular junction (NMJ). (A, B) The NMJ is composed of three elements: pre-synaptic (motor nerve terminal), intrasynaptic (synaptic basal lamina), and post-synaptic component (muscle fiber and muscle membrane) (Punga and Ruegg, 2012). When the action potential reaches the motor nerve terminal the calcium channels open and the calcium enters in the neuron and delivers ACh in the synaptic cleft. (C) AChR activates the DHPRs located in the sarcolemma and by induction the RyRs. Calcium released from the sarcoplasmic reticulum through the RyRs binds to troponin C and allows cross-bridge cycling and force production.
Mentions: The reason for a progressive impairment of the re-innervation process with aging is unknown, but some lines of evidence point to changes that occur with aging in the neuromuscular junction (NMJ), which is the synaptic interface between a branch of a motor neuron and muscle cells. The NMJ is composed of three elements: pre-synaptic (motor nerve terminal), intrasynaptic (synaptic basal lamina), and post-synaptic part (muscle fiber and muscle membrane) (Punga and Ruegg, 2012). When an action potential reaches the pre-synaptic element, voltage-dependent calcium channels open allowing calcium to enter the neuron and trigger the delivery of acetylcholine (ACh) in the synaptic cleft. Acetylcholine triggers nicotin acetylcholine receptors (nAChR) located in the post-synaptic membrane to produce an action potential, which in turn, activates voltage-gated dihydropyridine receptors (DHPRs) located in the sarcolemma and by induction, ryanodine receptors (RyRs). Of note, the post-synaptic membrane presents folds that expand its area. Calcium released from the sarcoplasmic reticulum through the RyRs binds to troponin C and allows cross-bridge cycling and force production (Figure 1).

Bottom Line: Aging is associated with a progressive loss of muscle mass and strength and a decline in neurophysiological functions.However, whether changes in the NMJ precede or follow the decline of muscle mass and strength remains unresolved.Many factors such as mitochondrial dysfunction, oxidative stress, inflammation, changes in the innervation of muscle fibers, and mechanical properties of the motor units probably perform an important role in NMJ degeneration and muscle mass and strength decline in late life.

View Article: PubMed Central - PubMed

Affiliation: Translational Gerontology Branch, National Institute on Aging, Intramural Research Program, National Institutes of Health , Baltimore, MD , USA ; Longitudinal Studies Section, Baltimore Longitudinal Study of Aging, National Institute on Aging, National Institutes of Health , Baltimore, MD , USA.

ABSTRACT
Aging is associated with a progressive loss of muscle mass and strength and a decline in neurophysiological functions. Age-related neuromuscular junction (NMJ) plays a key role in musculoskeletal impairment that occurs with aging. However, whether changes in the NMJ precede or follow the decline of muscle mass and strength remains unresolved. Many factors such as mitochondrial dysfunction, oxidative stress, inflammation, changes in the innervation of muscle fibers, and mechanical properties of the motor units probably perform an important role in NMJ degeneration and muscle mass and strength decline in late life. This review addresses the primary events that might lead to NMJ dysfunction with aging, including studies on biomarkers, signaling pathways, and animal models. Interventions such as caloric restriction and exercise may positively affect the NMJ through this mechanism and attenuate the age-related progressive impairment in motor function.

No MeSH data available.


Related in: MedlinePlus