scholarly journals Age-Related Alterations at Neuromuscular Junction: Role of Oxidative Stress and Epigenetic Modifications

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1307
Author(s):  
Gabriella Dobrowolny ◽  
Alessandra Barbiera ◽  
Gigliola Sica ◽  
Bianca Maria Scicchitano
Keyword(s):  
Neuromuscular Junction ◽  
Neuromuscular Junctions ◽  
Epigenetic Modifications ◽  
Neuromuscular System ◽  
Molecular Alterations ◽  
Age Related ◽  
Fiber Number ◽  
Physical Abilities ◽  
Effects Of Aging

With advancing aging, a decline in physical abilities occurs, leading to reduced mobility and loss of independence. Although many factors contribute to the physio-pathological effects of aging, an important event seems to be related to the compromised integrity of the neuromuscular system, which connects the brain and skeletal muscles via motoneurons and the neuromuscular junctions (NMJs). NMJs undergo severe functional, morphological, and molecular alterations during aging and ultimately degenerate. The effect of this decline is an inexorable decrease in skeletal muscle mass and strength, a condition generally known as sarcopenia. Moreover, several studies have highlighted how the age-related alteration of reactive oxygen species (ROS) homeostasis can contribute to changes in the neuromuscular junction morphology and stability, leading to the reduction in fiber number and innervation. Increasing evidence supports the involvement of epigenetic modifications in age-dependent alterations of the NMJ. In particular, DNA methylation, histone modifications, and miRNA-dependent gene expression represent the major epigenetic mechanisms that play a crucial role in NMJ remodeling. It is established that environmental and lifestyle factors, such as physical exercise and nutrition that are susceptible to change during aging, can modulate epigenetic phenomena and attenuate the age-related NMJs changes. This review aims to highlight the recent epigenetic findings related to the NMJ dysregulation during aging and the role of physical activity and nutrition as possible interventions to attenuate or delay the age-related decline in the neuromuscular system.

Aging, Attention, and Bimanual Coordination

2002 ◽  
Vol 21 (4) ◽  
pp. 549-557 ◽  
Author(s):  
Timothy D. Lee ◽  
Laurie R. Wishart ◽  
Jason E. Murdoch
Keyword(s):  
Older Adults ◽  
Bimanual Coordination ◽  
Alternative Explanation ◽  
Digit Number ◽  
Younger Adults ◽  
Age Related ◽  
Movement Frequency ◽  
Effects Of Aging ◽  
Coordination Patterns

ABSTRACTAlthough aging is normally associated with declines in motor performance, recent evidence suggests that older adults suffer no loss in some measures of bimanual coordination relative to younger adults. Two hypotheses for this finding were compared in the present research. One hypothesis was based on the assumption that these coordination patterns are automatic and relatively impervious to the effects of aging. An alternative explanation is that older adults maintain this level of bimanual coordination at a cost of increased attention demand. These hypotheses were tested in an experiment in which bimanual coordination patterns (in-phase and anti-phase) were paced at two metronome frequencies (1 and 2 Hz), either alone or together, with serial performance of an attention-demanding task (adding 3s to a two-digit number at a 1 Hz pace). The results of the study provided some support for both hypotheses. The automaticity view was supported only for the coordination patterns at the 1 Hz metronome frequency. Support for an attention allocation hypothesis was shown in the observed-movement frequency data, as older adults tended to sacrifice movement frequency at the 2 Hz metronome pace in order to maintain performance in the movement and counting tasks. These findings are discussed relative to recent accounts of the role of automaticity in the absence of age-related differences in the performance of cognitive tasks.

Endurance exercise modulates neuromuscular junction of C57BL/6NNia aging mice

1997 ◽  
Vol 83 (1) ◽  
pp. 59-66 ◽  
Author(s):  
Mohamed A. Fahim
Keyword(s):  
Neuromuscular Junction ◽  
Endurance Exercise ◽  
Neuromuscular Junctions ◽  
Safety Margin ◽  
Gluteus Maximus ◽  
Nerve Terminals ◽  
Quantal Content ◽  
Age Related ◽  
Endplate Potentials ◽  
Old Mice

Fahim, Mohamed A. Endurance exercise modulates neuromuscular junction of C57BL/6NNia aging mice. J. Appl. Physiol. 83(1): 59–66, 1997.—The effect of age and endurance exercise on the physiology and morphology of neuromuscular junctions (NMJ) of gluteus maximus muscle was studied in C57BL/6NNia mice. Mice were exercised, starting at 7 or 25 mo of age, at 28 m/min for 60 min/day, 5 days/wk for 12 wk, on a rodent treadmill. Intracellular recordings of spontaneous miniature endplate potentials (MEPP) and the quantal content of endplate potentials (EPP) were recorded from NMJ of 10- and 28-mo-old control and exercised mice. Endurance exercise resulted in significant increases in MEPP amplitudes (23%), quantal content, and safety margin, and a significant decrease in MEPP frequency of young mice, with no change in resting membrane potential or membrane capacitance. Three months of endurance exercise resulted in an increase in MEPP frequency (41%) and decreases in MEPP amplitudes (15%), quantal content, and safety margin of old mice. Endurance exercise resulted in significantly larger nerve terminals (24%) in young animals, suggesting functional adaptation. Nerve terminals in exercised 28-mo-old mice were smaller than in the corresponding control mice, an indication that exercise minimized age-related nerve terminal elaboration. It is concluded that the different physiological responses of young and old gluteus maximus muscles to endurance exercise parallel their morphological responses. This suggests that the mouse NMJ undergoes a process of physiological and morphological remodeling during aging, and such plasticity could be modulated differently by endurance exercise.

The Role of Cognition in Age-Related Hearing Loss

2007 ◽  
Vol 18 (07) ◽  
pp. 539-547 ◽  
Author(s):  
Fergus I.M. Craik
Keyword(s):  
Speech Processing ◽  
Cognitive Factors ◽  
Levels Of Analysis ◽  
Analysis Model ◽  
Top Down ◽  
Age Related ◽  
Effects Of Aging ◽  
Age Related Hearing Loss ◽  
Processing Framework

The article presents a commentary on the accompanying six papers from the perspective of a cognitive psychologist. Treisman's (1964, 1969) levels of analysis model of selective attention is suggested as a framework within which the interactions between 'bottom-up' auditory factors and 'top-down' cognitive factors may be understood. The complementary roles of auditory and cognitive aspects of hearing are explored, and their mutually compensatory properties discussed. The findings and ideas reported in the six accompanying papers fit well into such a 'levels of processing' framework, which may therefore be proposed as a model for understanding the effects of aging on speech processing and comprehension. El artículo presenta un comentario sobre los seis trabajos acompañantes desde la perspectiva de un psicólogo de la cognición. Se sugiere el modelo de Treisman (1964, 1969) de niveles de análisis de la atención selectiva como el marco dentro del cuál las interacciones entre los factores de atención "de abajo hacia arriba" y los factores cognitivos de "de arriba hacia abajo" pueden ser comprendidos. Se exploran los papeles complementarios de los aspectos auditivos y cognitivos de la audición y se discuten sus mutuas propiedades compensatorias. Los hallazgos e ideas reportados en los seis trabajos acompañantes calzan bien en dicho marco de "niveles de procesamiento", los que puede, por tanto, ser propuestos como un modelo para comprender el efecto del envejecimiento para el procesamiento y la comprensión del lenguaje.

Different VAMP/Synaptobrevin Complexes for Spontaneous and Evoked Transmitter Release at the Crayfish Neuromuscular Junction

1998 ◽  
Vol 80 (6) ◽  
pp. 3233-3246 ◽  
Author(s):  
Shao-Ying Hua ◽  
Dorota A. Raciborska ◽  
William S. Trimble ◽  
Milton P. Charlton
Keyword(s):  
Neuromuscular Junction ◽  
Transmitter Release ◽  
Neurotransmitter Release ◽  
Action Potentials ◽  
Neuromuscular Junctions ◽  
Spontaneous Release ◽  
Intracellular Ca ◽  
Crayfish Neuromuscular Junction ◽  
Evoked Transmitter Release

Hua, Shao-Ying, Dorota A. Raciborska, William S. Trimble, and Milton P. Charlton. Different VAMP/synaptobrevin complexes for spontaneous and evoked transmitter release at the crayfish neuromuscular junction. J. Neurophysiol. 80: 3233–3246, 1998. Although vesicle-associated membrane protein (VAMP/synaptobrevin) is essential for evoked neurotransmitter release, its role in spontaneous transmitter release remains uncertain. For instance, many studies show that tetanus toxin (TeNT), which cleaves VAMP, blocks evoked transmitter release but leaves some spontaneous transmitter release. We used recombinant tetanus and botulinum neurotoxin catalytic light chains (TeNT-LC, BoNT/B-LC, and BoNT/D-LC) to examine the role of VAMP in spontaneous transmitter release at neuromuscular junctions (nmj) of crayfish. Injection of TeNT-LC into presynaptic axons removed most of the VAMP immunoreactivity and blocked evoked transmitter release without affecting nerve action potentials or Ca2+ influx. The frequency of spontaneous transmitter release was little affected by the TeNT-LC when the evoked transmitter release had been blocked by >95%. The spontaneous transmitter release left after TeNT-LC treatment was insensitive to increases in intracellular Ca2+. BoNT/B-LC, which cleaves VAMP at the same site as TeNT-LC but uses a different binding site, also blocked evoked release but had minimal effect on spontaneous release. However, BoNT/D-LC, which cleaves VAMP at a different site from the other two toxins but binds to the same position on VAMP as TeNT, blocked both evoked and spontaneous transmitter release at similar rates. The data indicate that different VAMP complexes are employed for evoked and spontaneous transmitter release; the VAMP used in spontaneous release is not readily cleaved by TeNT or BoNT/B. Because the exocytosis that occurs after the action of TeNT cannot be increased by increased intracellular Ca2+, the final steps in neurotransmitter release are Ca2+ independent.

Effects of Aging and Reduced Relative Frequency of Knowledge of Results on Learning a Motor Skill

1997 ◽  
Vol 84 (3) ◽  
pp. 1107-1122 ◽  
Author(s):  
Laurie R. Wishart ◽  
Timothy D. Lee
Keyword(s):  
Older Adults ◽  
Motor Skill ◽  
Relative Frequency ◽  
Learning Task ◽  
Performance Information ◽  
Knowledge Of Results ◽  
Age Related ◽  
Effects Of Aging ◽  
Specific Timing

Although there is evidence for age-related changes in both cognition and motor control, very little is known about the effect of age on learning of new motor skills. The present experiment addressed the interaction between aging and the role of knowledge of results (KR) on a motor learning task. Using a three-segment task on which each segment had specific timing goals, three different manipulations of relative frequency of information about performance were compared in younger and older adults. The three conditions were (a) 100% KR in which information about performance on each segment was provided after every trial, (b) 67% KR in which the performance information was faded over trials, and (c) 67% KR in which the performance information was faded over the segments within each trial. Following 90 acquisition trials, all subjects performed retention, transfer, and reacquisition tests. There were age-related differences for movement accuracy and consistency on acquisition and on the retention tests but not on the transfer test. However, none of these differences interacted with the frequency of KR manipulations. Surprisingly, there was no effect due to the fading schedules of KR. In general, these results indicated that younger and older adults use KR in a similar way to learn a motor skill.

scholarly journals The aging neuromuscular system and motor performance

2016 ◽  
Vol 121 (4) ◽  
pp. 982-995 ◽  
Author(s):  
Sandra K. Hunter ◽  
Hugo M. Pereira ◽  
Kevin G. Keenan
Keyword(s):  
Motor Unit ◽  
Motor Performance ◽  
Neuromuscular Junctions ◽  
Myosin Heavy Chain Isoforms ◽  
Motor Unit Action Potential ◽  
Neuromuscular System ◽  
Cross Sectional ◽  
Very Old ◽  
Age Related ◽  
Age Related Changes

Age-related changes in the basic functional unit of the neuromuscular system, the motor unit, and its neural inputs have a profound effect on motor function, especially among the expanding number of old (older than ∼60 yr) and very old (older than ∼80 yr) adults. This review presents evidence that age-related changes in motor unit morphology and properties lead to impaired motor performance that includes 1) reduced maximal strength and power, slower contractile velocity, and increased fatigability; and 2) increased variability during and between motor tasks, including decreased force steadiness and increased variability of contraction velocity and torque over repeat contractions. The age-related increase in variability of motor performance with aging appears to involve reduced and more variable synaptic inputs that drive motor neuron activation, fewer and larger motor units, less stable neuromuscular junctions, lower and more variable motor unit action potential discharge rates, and smaller and slower skeletal muscle fibers that coexpress different myosin heavy chain isoforms in the muscle of older adults. Physical activity may modify motor unit properties and function in old men and women, although the effects on variability of motor performance are largely unknown. Many studies are of cross-sectional design, so there is a tremendous opportunity to perform high-impact and longitudinal studies along the continuum of aging that determine 1) the influence and cause of the increased variability with aging on functional performance tasks, and 2) whether lifestyle factors such as physical exercise can minimize this age-related variability in motor performance in the rapidly expanding numbers of very old adults.

scholarly journals Plum is a novel regulator of synaptic function and muscle size in D. melanogaster

2018 ◽  
Author(s):  
Hrvoje Augustin ◽  
Jereme G. Spiers ◽  
Nathaniel S. Woodling ◽  
Joern R. Steinert ◽  
Linda Partridge
Keyword(s):  
Body Weight ◽  
Neuromuscular Junction ◽  
Synaptic Function ◽  
Negative Regulator ◽  
Therapeutic Interventions ◽  
Muscle Size ◽  
Model Organisms ◽  
Neuromuscular System ◽  
Age Related ◽  
And Function

ABSTRACTAlterations in the neuromuscular system underlie several neuromuscular diseases and play critical roles in the development of sarcopenia, the age-related loss of muscle mass and function. Mammalian Myostatin (MST) and GDF11, members of the TGF-β superfamily of growth factors, are powerful regulators of muscle size in both model organisms and humans. Myoglianin (MYO), the Drosophila homolog of MST and GDF11, is a strong inhibitor of synaptic function and structure at the neuromuscular junction (NMJ), and a negative regulator of body weight and muscle size and function in flies. Here, we identified Plum, a cell surface immunoglobulin homologous to mammalian developmental regulators Protogenin and Nope, as a modulator of MYO function in the larval neuromuscular system. Reduction of Plum specifically in the larval body-wall muscles abolishes the previously demonstrated positive effect of attenuated MYO signalling on both muscle size and neuromuscular junction structure and function, likely by de-sequestrating the remaining MYO. In addition, downregulation of Plum on its own results in decreased synaptic strength and body weight, classifying Plum as a (novel) regulator of neuromuscular function and body (muscle) size. These findings offer new insights into possible regulatory mechanisms behind ageing- and disease-related neuromuscular dysfunctions in humans and identify potential targets for therapeutic interventions.

N-cadherin expression in developing, adult and denervated chicken neuromuscular system: accumulations at both the neuromuscular junction and the node of Ranvier

Development ◽  
1994 ◽  
Vol 120 (1) ◽  
pp. 1-11 ◽  
Author(s):  
C. Cifuentes-Diaz ◽  
M. Nicolet ◽  
D. Goudou ◽  
F. Rieger ◽  
R.M. Mege
Keyword(s):  
Neuromuscular Junction ◽  
Schwann Cells ◽  
Basal Lamina ◽  
Cellular Localization ◽  
Node Of Ranvier ◽  
Muscle Fibres ◽  
Neuromuscular System ◽  
Distal Stump ◽  
Denervated Muscle

N-cadherin, a member of the Ca(2+)-dependent cell adhesion molecule family plays essential roles in morphogenesis and histogenesis. N-cadherin has been shown in vitro to promote myoblast fusion and neurite outgrowth. We report here the cellular localization of N-cadherin during development and regeneration of the chick neuromuscular system. N-cadherin was uniformly expressed along the surface of myoblasts and myotubes of E6 limb muscles. Later, as synaptogenesis and secondary myogenesis proceeded, N-cadherin expression was down-regulated and restricted to some large-diameter fibres, then to the areas of contact between few myofibres and subsequently disappeared by embryonic day 17, suggesting that this cadherin may be implicated predominantly in fusion of primary myoblasts and, at lower degree, of secondary myoblasts. The presence of N-cadherin in muscle during the period of nerve trunk ingrowth and its down-regulation after synaptogenesis suggests that this molecule might be implicated in both processes. N-cadherin became accumulated at the neuromuscular junction only a few days after the first synaptic contacts were established and remained at the adult neuromuscular junction, suggesting a role of this molecule in the stabilization of the mature neuromuscular junction. In sciatic nerve, the level of N-cadherin expression remained unchanged from hatching to adult life. N-cadherin was widely distributed on the surface of myelinated fibres and on myelinating Schwann cells: in addition, it was concentrated at the node of Ranvier. At the ultrastructural level, the molecule was detected inside, at the surface and in the basal lamina of Schwann cells and also associated with endoneurial collagen. These observations suggest a role of N-cadherin in the structuring and stabilization of the myelin sheaths. After nerve injury, N-cadherin continued to be expressed by proliferating Schwann cells in the distal stump providing a substratum for regenerating axons. N-cadherin reappeared at the surface of denervated muscle fibres without disappearing from the former synaptic sites. It was detected not only in the sarcoplasm and on sarcolemma of denervated muscle fibres, but also in the basal lamina and in the extracellular matrix. The reexpression of N-cadherin at the surface of denervated muscle fibres suggests a role for this molecule in muscle reinnervation. The presence of N-cadherin in basal lamina and its association with collagen fibres raise questions about the release of N-cadherin in the extracellular space and the existence of a putative heterophilic ligand for N-cadherin.

scholarly journals Apoptosis in skeletal muscle with aging

2002 ◽  
Vol 282 (2) ◽  
pp. R519-R527 ◽  
Author(s):  
Amie Dirks ◽  
Christiaan Leeuwenburgh
Keyword(s):  
Skeletal Muscle ◽  
Cytochrome C ◽  
Gastrocnemius Muscle ◽  
Caspase 3 ◽  
Age Related ◽  
Fiber Number ◽  
Old Rats ◽  
Cytosolic Cytochrome

Sarcopenia may be partly due to a loss in total fiber number by apoptosis. We have investigated age-related alterations in the mitochondria-mediated pathway leading to apoptosis in the gastrocnemius muscle from 6-mo-old and 24-mo-old male Fisher 344 rats. Apoptosis (mono- and oligonucleosome fragmentation) in the gastrocnemius muscle was increased by 50% in the old rats compared with the adult animals. Furthermore, there was a significant correlation between cytosolic cytochrome c and caspase-3 activity, although neither cytochrome c nor caspase-3 activity increased significantly with age. Furthermore, there was a significant correlation between caspase-3 activity and mono- and oligonucleosome fragmentation in the old rats only. Mitochondrial Bcl-2 and Bax were not altered with age. In vitro experiments demonstrated that activation of the caspase cascade in skeletal muscle might be limited by procaspase-9 activation. This is the first study to explore the role of apoptosis in sarcopenia and suggests that subtle changes in apoptosis are involved.

scholarly journals Loss of adult skeletal muscle stem cells drives age-related neuromuscular junction degeneration

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Wenxuan Liu ◽  
Alanna Klose ◽  
Sophie Forman ◽  
Nicole D Paris ◽  
Lan Wei-LaPierre ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Stem Cell ◽  
Neuromuscular Junction ◽  
Neuromuscular Junctions ◽  
Aged Mouse ◽  
Muscle Stem Cell ◽  
Adult Skeletal Muscle ◽  
Muscle Stem Cells ◽  
Age Related

Neuromuscular junction degeneration is a prominent aspect of sarcopenia, the age-associated loss of skeletal muscle integrity. Previously, we showed that muscle stem cells activate and contribute to mouse neuromuscular junction regeneration in response to denervation (Liu et al., 2015). Here, we examined gene expression profiles and neuromuscular junction integrity in aged mouse muscles, and unexpectedly found limited denervation despite a high level of degenerated neuromuscular junctions. Instead, degenerated neuromuscular junctions were associated with reduced contribution from muscle stem cells. Indeed, muscle stem cell depletion was sufficient to induce neuromuscular junction degeneration at a younger age. Conversely, prevention of muscle stem cell and derived myonuclei loss was associated with attenuation of age-related neuromuscular junction degeneration, muscle atrophy, and the promotion of aged muscle force generation. Our observations demonstrate that deficiencies in muscle stem cell fate and post-synaptic myogenesis provide a cellular basis for age-related neuromuscular junction degeneration and associated skeletal muscle decline.

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