scholarly journals Age Related Changes in Motor Function (II). Decline in Motor Performance Outcomes

2020 ◽  
Author(s):  
Rui Wu ◽  
Massimiliano Ditroilo ◽  
Eamonn Delahunt ◽  
Giuseppe De Vito
Keyword(s):  
Skeletal Muscle ◽  
Motor Neurons ◽  
Muscle Fiber ◽  
Motor Performance ◽  
Motor Units ◽  
Performance Outcomes ◽  
Isometric Contractions ◽  
Contributing Factors ◽  
Shortening Velocity ◽  
Age Related

AbstractAge-related impairments in motor performance are caused by a deterioration in mechanical and neuromuscular functions, which have been investigated from the macro-level of muscle-tendon unit to the micro-level of the single muscle fiber. When compared to the healthy young skeletal muscle, aged skeletal muscle is: (1) weaker, slower and less powerful during the performance of voluntary contractions; (2) less steady during the performance of isometric contractions, particularly at low levels of force; and (3) less susceptible to fatigue during the performance of sustained isometric contractions, but more susceptible to fatigue during the performance of high-velocity dynamic contractions. These impairments have been discussed to be mainly the result of: a) loss of muscle mass and selective atrophy of type II muscle fibers; b) altered tendon mechanical properties (decreased tendon stiffness); c) reduced number and altered function of motor units; d) slower muscle fiber shortening velocity; e) increased oscillation in common synaptic input to motor neurons; and f) altered properties and activity of sarcoplasmic reticulum. In this second part of a two-part review we have detailed the age-related impairments in motor performance with a reference to the most important mechanical and neuromuscular contributing factors.

Effects of Ageing on the Motor Unit: A Brief Review

1993 ◽  
Vol 18 (4) ◽  
pp. 331-358 ◽  
Author(s):  
Timothy J. Doherty ◽  
Anthony A. Vandervoort ◽  
William F. Brown
Keyword(s):  
Skeletal Muscle ◽  
Relaxation Times ◽  
Motor Units ◽  
The Elderly ◽  
Key Words Skeletal Muscle ◽  
Current State ◽  
Age Related ◽  
Human Motor ◽  
Muscle Groups ◽  
And Function

This review briefly summarizes the current state of knowledge regarding age related changes in skeletal muscle, followed by a more in-depth review of ageing effects on animal and human motor units (MUs). Ageing in humans is generally associated with reductions in muscle mass (atrophy), leading to reduced voluntary and electrically evoked contractile strength by the 7th decade for most muscle groups studied. As well, contraction and one-half relaxation times are typically prolonged in muscles of the elderly. Evidence from animal and human studies points toward age associated MU loss as the primary mechanism for muscle atrophy, and such losses may be greatest among the largest and fastest MUs. However, based on studies in animals and humans, it appears that at least some of the surviving MUs are able to partially compensate for MU losses, as indicated by an increase in the average MU size with age. The fact that muscles in the elderly have fewer, but on average larger and slower, MUs has important implications for motor control and function in this population. Key words: skeletal muscle, motor neuron, motor axon, contractile properties, adaptation

scholarly journals Reduced Endplate Currents Underlie Motor Unit Dysfunction in Canine Motor Neuron Disease

2002 ◽  
Vol 88 (6) ◽  
pp. 3293-3304 ◽  
Author(s):  
Mark M. Rich ◽  
Robert. F. Waldeck ◽  
Linda C. Cork ◽  
Rita J. Balice-Gordon ◽  
Robert E. W. Fyffe ◽  
...  
Keyword(s):  
Motor Neuron ◽  
Motor Neuron Disease ◽  
Motor Unit ◽  
Conduction Velocity ◽  
Motor Neurons ◽  
Muscle Fiber ◽  
Muscular Atrophy ◽  
Motor Units ◽  
Postnatal Maturation ◽  
Axonal Conduction

Hereditary canine spinal muscular atrophy (HCSMA) is an autosomal dominant degenerative disorder of motor neurons. In homozygous animals, motor units produce decreased force output and fail during repetitive activity. Previous studies suggest that decreased efficacy of neuromuscular transmission underlies these abnormalities. To examine this, we recorded muscle fiber endplate currents (EPCs) and found reduced amplitudes and increased failures during nerve stimulation in homozygotes compared with wild-type controls. Comparison of EPC amplitudes with muscle fiber current thresholds indicate that many EPCs from homozygotes fall below threshold for activating muscle fibers but can be raised above threshold following potentiation. To determine whether axonal abnormalities might play a role in causing motor unit dysfunction, we examined the postnatal maturation of axonal conduction velocity in relation to the appearance of tetanic failure. We also examined intracellularly labeled motor neurons for evidence of axonal neurofilament accumulations, which are found in many instances of motor neuron disease including HCSMA. Despite the appearance of tetanic failure between 90 and 120 days, average motor axon conduction velocity increased with age in homozygotes and achieved adult levels. Normal correlations between motor neuron properties (including conduction velocity) and motor unit properties were also observed. Labeled proximal motor axons of several motor neurons that supplied failing motor units exhibited little or no evidence of axonal swellings. We conclude that decreased release of transmitter from motor terminals underlies motor unit dysfunction in HCSMA and that the mechanisms determining the maturation of axonal conduction velocity and the pattern of correlation between motor neuron and motor unit properties do not contribute to the appearance or evolution of motor unit dysfunction.

scholarly journals The Neuromuscular Junction: Roles in Aging and Neuromuscular Disease

2021 ◽  
Vol 22 (15) ◽  
pp. 8058
Author(s):  
Shama R. Iyer ◽  
Sameer B. Shah ◽  
Richard M. Lovering
Keyword(s):  
Skeletal Muscle ◽  
Neuromuscular Junction ◽  
Motor Neuron ◽  
Muscle Fiber ◽  
Short Review ◽  
Muscle Disease ◽  
Contributing Factors ◽  
Functional Changes ◽  
Disease Modifier ◽  
Electrical Impulses

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.

scholarly journals Microbiopsy Sampling for Examining Age-Related Differences in Skeletal Muscle Fiber Morphology and Composition

2022 ◽  
Vol 12 ◽  
Author(s):  
Garrett M. Hester ◽  
Trisha A. VanDusseldorp ◽  
Phuong L. Ha ◽  
Kaveh Kiani ◽  
Alex A. Olmos ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Fiber ◽  
Vastus Lateralis ◽  
Peak Torque ◽  
Type I ◽  
Type Ii ◽  
Fiber Morphology ◽  
Specific Strength ◽  
Age Related ◽  
Whole Muscle

Introduction: The increasingly popular microbiopsy is an appealing alternative to the more invasive Bergström biopsy given the challenges associated with harvesting skeletal muscle in older populations. Parameters of muscle fiber morphology and composition derived from the microbiopsy have not been compared between young and older adults.Purpose: The purpose of this study was to examine muscle fiber morphology and composition in young (YM) and older (OM) males using the microbiopsy sampling technique. A secondary aim was to determine if specific strength is associated with serum levels of C-terminal agrin fragment [CAF; an indicator of neuromuscular junction (NMJ) degradation].Methods: Thirty healthy, YM (n = 15, age = 20.7 ± 2.2 years) and OM (n = 15, age = 71.6 ± 3.9 years) underwent ultrasound imaging to determine whole-muscle cross-sectional area (CSA) of the vastus lateralis and rectus femoris as well as isometric and isokinetic (60°⋅s–1 and 180°⋅s–1) peak torque testing of the knee extensors. Microbiopsy samples of the vastus lateralis were collected from 13 YM and 11 OM, and immunofluorescence was used to calculate CSA and proportion of type I and type II fibers.Results: Peak torque was lower in OM at all velocities (p ≤ 0.001; d = 1.39–1.86) but only lower at 180°⋅s–1 (p = 0.003; d = 1.23) when normalized to whole-muscle CSA. Whole-muscle CSA was smaller in OM (p = 0.001; d = 1.34), but atrophy was not present at the single fiber level (p > 0.05). Per individual, ∼900 fibers were analyzed, and type I fiber CSA was larger (p = 0.05; d = 0.94) in OM which resulted in a smaller type II/I fiber CSA ratio (p = 0.015; d = 0.95). CAF levels were not sensitive to age (p = 0.159; d = 0.53) nor associated with specific strength or whole-muscle CSA in OM.Conclusion: The microbiopsy appears to be a viable alternative to the Bergström biopsy for histological analyses of skeletal muscle in older adults. NMJ integrity was not influential for age-related differences in specific strength in our healthy, non-sarcopenic older sample.

scholarly journals Single nuclei profiling identifies cell specific markers of skeletal muscle aging, sarcopenia and senescence

2021 ◽  
Author(s):  
Kevin Perez ◽  
Julia McGirr ◽  
Chandani Limbad ◽  
Ryosuke Doi ◽  
Joshua P Nederveen ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Motor Neurons ◽  
Transcriptome Profiling ◽  
Cell Types ◽  
Small Population ◽  
Human Populations ◽  
Rna Seq ◽  
Spatial Profiling ◽  
Age Related ◽  
Skeletal Muscle Aging

AbstractAging is accompanied by a loss of muscle mass and function, termed sarcopenia, which causes numerous morbidities and economic burdens in human populations. Mechanisms implicated in age-related sarcopenia include inflammation, muscle stem cell depletion, mitochondrial dysfunction and loss of motor neurons, but whether there are key drivers of sarcopenia is not yet known. To gain deeper insights into age-related sarcopenia, we performed transcriptome profiling on lower limb muscle biopsies from 72 young, old and sarcopenic subjects using bulk RNA-seq (N = 72) and single-nuclei RNA-seq (N = 17). This combined approach revealed novel changes in gene expression that occur with age and sarcopenia in multiple cell types comprising mature skeletal muscle. Notably, we found increased expression of the genes MYH8 and PDK4, and decreased expression of the gene IGFN1, in old muscle. We validated key genes in fixed human muscle tissue using digital spatial profiling. We also identified a small population of nuclei that express CDKN1A, present only in aged samples, consistent with p21-driven senescence in this subpopulation. Overall, our findings identify unique cellular subpopulations in aged and sarcopenic skeletal muscle, which will facilitate the development of new therapeutic strategies to combat age-related sarcopenia.

scholarly journals Use it or lose it: tonic activity of slow motoneurons promotes their survival and preferentially increases slow fiber-type groupings in muscles of old lifelong recreational sportsmen

2016 ◽  
Vol 26 (4) ◽  
Author(s):  
Simone Mosole ◽  
Ugo Carraro ◽  
Helmut Kern ◽  
Stefan Loefler ◽  
Sandra Zampieri
Keyword(s):  
Motor Neurons ◽  
Fiber Type ◽  
Functional Decline ◽  
Muscle Fibers ◽  
Motor Units ◽  
The Body ◽  
Age Related ◽  
Immuno Histochemistry ◽  
High Level ◽  
And Function

Histochemistry, immuno-histochemistry, gel electrophoresis of single muscle fibers and electromyography of aging muscles and nerves suggest that: i) denervation contributes to muscle atrophy, ii) impaired mobility accelerates the process, and iii) lifelong running protects against loss of motor units. Recent corroborating results on the muscle effects of Functional Electrical Stimulation (FES) of aged muscles will be also mentioned, but we will in particular discuss how and why a lifelong increased physical activity sustains reinnervation of muscle fibers. By analyzing distribution and density of muscle fibers co-expressing fast and slow Myosin Heavy Chains (MHC) we are able to distinguish the transforming muscle fibers due to activity related plasticity, to those that adapt muscle fiber properties to denervation and reinnervation. In muscle biopsies from septuagenarians with a history of lifelong high-level recreational activity we recently observed in comparison to sedentary seniors: 1. decreased proportion of small-size angular myofibers (denervated muscle fibers); 2. considerable increase of fiber-type groupings of the slow type (reinnervated muscle fibers); 3. sparse presence of muscle fibers co-expressing fast and slow MHC. Immuno-histochemical characteristics fluctuate from those with scarce fiber-type modulation and groupings to almost complete transformed muscles, going through a process in which isolated fibers co-expressing fast and slow MHC fill the gaps among fiber groupings. Data suggest that lifelong high-level exercise allows the body to adapt to the consequences of the age-related denervation and that it preserves muscle structure and function by saving otherwise lost muscle fibers through recruitment to different slow motor units. This is an opposite behavior of that described in long term denervated or resting muscles. These effects of lifelong high level activity seems to act primarily on motor neurons, in particular on those always more active, i.e., on the slow motoneurons. The preferential reinnervation that follows along decades of increased activity maintains neuron and myofibers. All together the results open interesting perspectives for applications of FES and electroceuticals for rejuvenation of aged muscles to delay functional decline and loss of independence that are unavoidable burdens of advanced aging. Trial Registration: ClinicalTrials.gov: NCT01679977.

Force Steadiness: From Motor Units to Voluntary Actions

Physiology ◽  
2021 ◽  
Vol 36 (2) ◽  
pp. 114-130 ◽  
Author(s):  
Roger M. Enoka ◽  
Dario Farina
Keyword(s):  
Motor Function ◽  
Motor Neurons ◽  
Motor Units ◽  
Isometric Contractions ◽  
Strongly Correlated ◽  
Synaptic Inputs ◽  
Force Steadiness ◽  
Spinal Motor Neurons ◽  
Spinal Motor

Voluntary actions are controlled by the synaptic inputs that are shared by pools of spinal motor neurons. The slow common oscillations in the discharge times of motor units due to these synaptic inputs are strongly correlated with the fluctuations in force during submaximal isometric contractions (force steadiness) and moderately associated with performance scores on some tests of motor function. However, there are key gaps in knowledge that limit the interpretation of differences in force steadiness.

Cross talk between androgen and Wnt signaling potentially contributes to age-related skeletal muscle atrophy in rats

2018 ◽  
Vol 125 (2) ◽  
pp. 486-494 ◽  
Author(s):  
Petey W. Mumford ◽  
Matthew A. Romero ◽  
Xuansong Mao ◽  
C. Brooks Mobley ◽  
Wesley C. Kephart ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Expression ◽  
Wnt Signaling ◽  
Muscle Fiber ◽  
Muscle Loss ◽  
Fischer 344 Rats ◽  
Protein Levels ◽  
Fischer 344 ◽  
Age Related ◽  
Fiber Size

We sought to determine whether age-related gastrocnemius muscle mass loss was associated with parallel decrements in androgen receptor (AR) or select Wnt signaling markers. To test this hypothesis, serum-free and total testosterone (TEST) and gastrocnemius AR and Wnt signaling markers were analyzed in male Fischer 344 rats that were 3, 6, 12, 18, and 24 mo (mo) old ( n = 9 per group). Free and total TEST was greatest in 6 mo rats, and AR protein and Wnt5 protein levels linearly declined with aging. There were associations between Wnt5 protein levels and relative gastrocnemius mass ( r = 0.395, P = 0.007) as well as AR and Wnt5 protein levels (r = 0.670, P < 0.001). We next tested the hypothesis that Wnt5 affects muscle fiber size by treating C2C12-derived myotubes with lower (75 ng/ml) and higher (150 ng/ml) concentrations of recombinant Wnt5a protein. Both treatments increased myotube size ( P < 0.05) suggesting this ligand may affect muscle fiber size in vivo. We next tested if Wnt5a protein levels were androgen-modulated by examining 10-mo-old male Fischer 344 rats ( n = 10–11 per group) that were orchiectomized and treated with testosterone-enanthate (TEST-E); trenbolone enanthate (TREN), a nonaromatizable synthetic testosterone analogue; or a vehicle (ORX only) for 4 wk. Interestingly, TEST-E and TREN treatments increased Wnt5a protein in the androgen-sensitive levator ani/bulbocavernosus muscle compared with ORX only ( P < 0.05). To summarize, aromatizable and nonaromatizable androgens increase Wnt5a protein expression in skeletal muscle, age-related decrements in muscle AR may contribute Wnt5a protein decrements, and our in vitro data imply this mechanism may contribute to age-related muscle loss. NEW & NOTEWORTHY Results from this study demonstrate androgen and Wnt5 protein expression decrease with aging, and this may be a mechanism involved with age-related muscle loss.

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