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Ageing Research Reviews Nov 2018Age-related loss of skeletal muscle mass and function, sarcopenia, is associated with physical frailty and increased risk of morbidity (chronic diseases), in addition to... (Review)
Review
Age-related loss of skeletal muscle mass and function, sarcopenia, is associated with physical frailty and increased risk of morbidity (chronic diseases), in addition to all-cause mortality. The loss of muscle mass occurs incipiently from middle-age (∼1%/year), and in severe instances can lead to a loss of ∼50% by the 8-9th decade of life. This review will focus on muscle deterioration with ageing and highlight the two underpinning mechanisms regulating declines in muscle mass and function: muscle fibre atrophy and muscle fibre loss (hypoplasia) - and their measurement. The mechanisms of muscle fibre atrophy in humans relate to imbalances in muscle protein synthesis (MPS) and breakdown (MPB); however, since there is limited evidence for basal alterations in muscle protein turnover, it would appear that "anabolic resistance" to fundamental environmental cues regulating diurnal muscle homeostasis (namely physical activity and nutrition), underlie age-related catabolic perturbations in muscle proteostasis. While the 'upstream' drivers of the desensitization of aged muscle to anabolic stimuli are poorly defined, they most likely relate to impaired efficiency of the conversion of nutritional/exercise stimuli into signalling impacting mRNA translation and proteolysis. Additionally, loss of muscle fibres has been shown in cadaveric studies using anatomical fibre counts, and from iEMG studies demonstrating motor unit loss, albeit with few molecular investigations of this in humans. We suggest that defining countermeasures against sarcopenia requires improved understandings of the co-ordinated regulation of muscle fibre atrophy and fibre loss, which are likely to be inextricably linked.
Topics: Aging; Animals; Exercise; Humans; Muscle Fibers, Skeletal; Muscle Proteins; Muscle Strength; Muscle, Skeletal; Muscular Atrophy; Nutritional Status; Sarcopenia
PubMed: 30048806
DOI: 10.1016/j.arr.2018.07.005 -
The American Journal of Sports Medicine Aug 2020Anterior cruciate ligament (ACL) injuries and reconstruction (ACLR) promote quadriceps muscle atrophy and weakness that can persist for years, suggesting the need for... (Randomized Controlled Trial)
Randomized Controlled Trial
Utility of Neuromuscular Electrical Stimulation to Preserve Quadriceps Muscle Fiber Size and Contractility After Anterior Cruciate Ligament Injuries and Reconstruction: A Randomized, Sham-Controlled, Blinded Trial.
BACKGROUND
Anterior cruciate ligament (ACL) injuries and reconstruction (ACLR) promote quadriceps muscle atrophy and weakness that can persist for years, suggesting the need for more effective rehabilitation programs. Whether neuromuscular electrical stimulation (NMES) can be used to prevent maladaptations in skeletal muscle size and function is unclear.
PURPOSE
To examine whether early NMES use, started soon after an injury and maintained through 3 weeks after surgery, can preserve quadriceps muscle size and contractile function at the cellular (ie, fiber) level in the injured versus noninjured leg of patients undergoing ACLR.
STUDY DESIGN
Randomized controlled trial; Level of evidence, 1.
METHODS
Patients (n = 25; 12 men/13 women) with an acute, first-time ACL rupture were randomized to NMES (5 d/wk) or sham (simulated microcurrent electrical nerve stimulation; 5 d/wk) treatment to the quadriceps muscles of their injured leg. Bilateral biopsies of the vastus lateralis were performed 3 weeks after surgery to measure skeletal muscle fiber size and contractility. Quadriceps muscle size and strength were assessed 6 months after surgery.
RESULTS
A total of 21 patients (9 men/12 women) completed the trial. ACLR reduced single muscle fiber size and contractility across all fiber types ( < .01 to < .001) in the injured compared with noninjured leg 3 weeks after surgery. NMES reduced muscle fiber atrophy ( < .01) through effects on fast-twitch myosin heavy chain (MHC) II fibers ( < .01 to < .001). NMES preserved contractility in slow-twitch MHC I fibers ( < .01 to < .001), increasing maximal contractile velocity ( < .01) and preserving power output ( < .01), but not in MHC II fibers. Differences in whole muscle strength between groups were not discerned 6 months after surgery.
CONCLUSION
Early NMES use reduced skeletal muscle fiber atrophy in MHC II fibers and preserved contractility in MHC I fibers. These results provide seminal, cellular-level data demonstrating the utility of the early use of NMES to beneficially modify skeletal muscle maladaptations to ACLR.
CLINICAL RELEVANCE
Our results provide the first comprehensive, cellular-level evidence to show that the early use of NMES mitigates early skeletal muscle maladaptations to ACLR.
REGISTRATION
NCT02945553 (ClinicalTrials.gov identifier).
Topics: Anterior Cruciate Ligament Injuries; Anterior Cruciate Ligament Reconstruction; Electric Stimulation Therapy; Female; Humans; Male; Muscle Contraction; Muscle Fibers, Skeletal; Muscle Strength; Organ Size; Quadriceps Muscle
PubMed: 32631074
DOI: 10.1177/0363546520933622 -
The FEBS Journal Oct 2018Different forms of myosin heavy chains (MyHCs), coded by a large family of sarcomeric MYH genes, are expressed in striated muscles. The generation of specific anti-MyHC... (Review)
Review
Different forms of myosin heavy chains (MyHCs), coded by a large family of sarcomeric MYH genes, are expressed in striated muscles. The generation of specific anti-MyHC antibodies has provided a powerful tool to define the fiber types present in skeletal muscles, their functional properties, their response to conditions that affect muscle plasticity and their changes in muscle disorders. Cardiomyocyte heterogeneity has been revealed by the serendipitous observation that different MyHCs are present in atrial and ventricular myocardium and in heart conduction tissue. Developmental MyHCs present in embryonic and fetal/neonatal skeletal muscle are re-expressed during muscle regeneration and can be used to identify regenerating fibers in muscle diseases. MyHC isoforms provide cell type-specific markers to identify the signaling pathways that control muscle cell identity and are an essential reference to interpret the results of single-cell transcriptomics and proteomics.
Topics: Animals; Antibodies, Monoclonal; Gene Expression Regulation, Developmental; Humans; Muscle Fibers, Skeletal; Muscle, Skeletal; Myosin Heavy Chains; Protein Isoforms
PubMed: 29761627
DOI: 10.1111/febs.14502 -
Wiley Interdisciplinary Reviews.... Jul 2016Skeletal muscle fibers are classified into fiber types, in particular, slow twitch versus fast twitch. Muscle fiber types are generally defined by the particular myosin... (Review)
Review
Skeletal muscle fibers are classified into fiber types, in particular, slow twitch versus fast twitch. Muscle fiber types are generally defined by the particular myosin heavy chain isoforms that they express, but many other components contribute to a fiber's physiological characteristics. Skeletal muscle fiber type can have a profound impact on muscle diseases, including certain muscular dystrophies and sarcopenia, the aging-induced loss of muscle mass and strength. These findings suggest that some muscle diseases may be treated by shifting fiber type characteristics either from slow to fast, or fast to slow phenotypes, depending on the disease. Recent studies have begun to address which components of muscle fiber types mediate their susceptibility or resistance to muscle disease. However, for many diseases it remains largely unclear why certain fiber types are affected. A substantial body of work has revealed molecular pathways that regulate muscle fiber type plasticity and early developmental muscle fiber identity. For instance, recent studies have revealed many factors that regulate muscle fiber type through modulating the activity of the muscle regulatory transcription factor MYOD1. Future studies of muscle fiber type development in animal models will continue to enhance our understanding of factors and pathways that may provide therapeutic targets to treat muscle diseases. WIREs Dev Biol 2016, 5:518-534. doi: 10.1002/wdev.230 For further resources related to this article, please visit the WIREs website.
Topics: Animals; Developmental Biology; Humans; Muscle Fibers, Skeletal; Muscular Diseases; Myosin Heavy Chains
PubMed: 27199166
DOI: 10.1002/wdev.230 -
Clinical Neurophysiology : Official... May 2021Describe and evaluate the concepts of near fiber electromyography (NFEMG), the features used, including near fiber motor unit potential (NFMUP) duration and dispersion,...
OBJECTIVE
Describe and evaluate the concepts of near fiber electromyography (NFEMG), the features used, including near fiber motor unit potential (NFMUP) duration and dispersion, which relate to motor unit distal axonal branch and muscle fiber conduction time dispersion, and NFMUP segment jitter, a new measure of the temporal variability of neuromuscular junction transmission (NMJ), and axonal branch and muscle fibre conduction for the near fibres (i.e. NF jitter), and the methods for obtaining their values.
METHODS
Trains of high-pass filtered motor unit potentials (MUPs) (i.e. NFMUP trains) were extracted from needle-detected EMG signals to assess changes in motor unit (MU) morphology and electrophysiology caused by neuromuscular disorders or ageing. Evaluations using simulated needle-detected EMG data were completed and example human data are presented.
RESULTS
NFEMG feature values can be used to detect axonal sprouting, conduction slowing and NMJ transmission delay as well as changes in MU fiber diameter variability, and NF jitter. These changes can be detected prior to alterations of MU size or numbers.
CONCLUSIONS
The evaluations clearly demonstrate and the example data support that NFMUP duration and dispersion reflect MU distal axonal branching, conduction slowing and NMJ transmission delay and/or MU fiber diameter variability and that NFMUP jiggle and segment jitter reflect NF jitter.
SIGNIFICANCE
NFEMG can detect early changes in MU morphology and/or electrophysiology and has the potential to augment clinical diagnosis and tracking of neuromuscular disorders.
Topics: Axons; Electromyography; Evoked Potentials, Motor; Humans; Muscle Fibers, Skeletal
PubMed: 33774377
DOI: 10.1016/j.clinph.2021.02.008 -
Proceedings of the National Academy of... Jan 2023Sarcopenia is distinct from normal muscle atrophy in that it is closely related to a shift in the muscle fiber type. Deficiency of the anabolic action of androgen on...
Sarcopenia is distinct from normal muscle atrophy in that it is closely related to a shift in the muscle fiber type. Deficiency of the anabolic action of androgen on skeletal muscles is associated with sarcopenia; however, the function of the androgen receptor (AR) pathway in sarcopenia remains poorly understood. We generated a mouse model (fast-twitch muscle-specific AR knockout [fmARKO] mice) in which the AR was selectively deleted in the fast-twitch muscle fibers. In young male mice, the deletion caused no change in muscle mass, but it reduced muscle strength and fatigue resistance and induced a shift in the soleus muscles from fast-twitch fibers to slow-twitch fibers (14% increase, = 0.02). After middle age, with the control mice, the male fmARKO mice showed much less muscle function, accompanied by lower hindlimb muscle mass; this phenotype was similar to the progression of sarcopenia. The bone mineral density of the femur was significantly reduced in the fmARKO mice, indicating possible osteosarcopenia. Microarray and gene ontology analyses revealed that in male fmARKO mice, there was downregulation of polyamine biosynthesis-related geneswhich was confirmed by liquid chromatography-tandem mass spectrometry assay and the primary cultured myofibers. None of the AR deletion-related phenotypes were observed in female fmARKO mice. Our findings showed that the AR pathway had essential muscle type- and sex-specific roles in the differentiation toward fast-twitch fibers and in the maintenance of muscle composition and function. The AR in fast-twitch muscles was the dominant regulator of muscle fiber-type composition and muscle function, including the muscle-bone relationship.
Topics: Mice; Male; Female; Animals; Sarcopenia; Receptors, Androgen; Muscle Fibers, Slow-Twitch; Muscle, Skeletal; Muscle Fibers, Fast-Twitch; Muscular Diseases; Phenotype; Mice, Knockout
PubMed: 36669097
DOI: 10.1073/pnas.2218032120 -
The Journal of Physiology Sep 2019Performing resistance exercise with heavier loads is often proposed to be necessary for the recruitment of larger motor units and activation of type II muscle fibres,... (Clinical Trial)
Clinical Trial
KEY POINTS
Performing resistance exercise with heavier loads is often proposed to be necessary for the recruitment of larger motor units and activation of type II muscle fibres, leading to type II fibre hypertrophy. Indirect measures [surface electromyography (EMG)] have been used to support this thesis, although we propose that lighter loads lifted to task failure (i.e. volitional fatigue) result in the similar activation of type II fibres. In the present study, participants performed resistance exercise to task failure with heavier and lighter loads with both a normal and longer repetition duration (i.e. time under tension). Type I and type II muscle fibre glycogen depletion was determined by neither load, nor repetition duration during resistance exercise performed to task failure. Surface EMG amplitude was not related to muscle fibre glycogen depletion or anabolic signalling; however, muscle fibre glycogen depletion and anabolic signalling were related. Performing resistance exercise to task failure, regardless of load lifted or repetition duration, necessitates the activation of type II muscle fibres.
ABSTRACT
Heavier loads (>60% of maximal strength) are considered to be necessary during resistance exercise (RE) to activate and stimulate hypertrophy of type II fibres. Support for this proposition comes from observation of higher surface electromyography (EMG) amplitudes during RE when lifting heavier vs. lighter loads. We aimed to determine the effect of RE, to task failure, with heavier vs. lighter loads and shorter or longer repetition durations on: EMG-derived variables, muscle fibre activation, and anabolic signalling. Ten recreationally-trained young men performed four unilateral RE conditions randomly on two occasions (two conditions, one per leg per visit). Muscle biopsies were taken from the vastus lateralis before and one hour after RE. Broadly, total time under load, number of repetitions, exercise volume, EMG amplitude (at the beginning and end of each set) and total EMG activity were significantly different between conditions (P < 0.05); however, neither glycogen depletion (in both type I and type II fibres), nor phosphorylation of relevant signalling proteins showed any difference between conditions. We conclude that muscle fibre activation and subsequent anabolic signalling are independent of load, repetition duration and surface EMG amplitude when RE is performed to task failure. The results of the present study provide evidence indicating that type I and type II fibres are activated when heavier and lighter loads are lifted to task failure. We propose that our results explain why RE training with higher or lower loads, when loads are lifted to task failure, leads to equivalent muscle hypertrophy and occurs in both type I and type II fibres.
Topics: Adult; Electromyography; Exercise; Humans; Male; Muscle Contraction; Muscle Fibers, Fast-Twitch; Muscle Fibers, Slow-Twitch; Muscle Strength; Resistance Training; Young Adult
PubMed: 31294822
DOI: 10.1113/JP278056 -
Oncotarget Mar 2017
Topics: Animals; Electromyography; Electrophysiological Phenomena; Humans; Muscle Denervation; Muscle Fibers, Skeletal; Muscles; Nerve Regeneration; Neurons
PubMed: 28407699
DOI: 10.18632/oncotarget.15757 -
Proceedings of the National Academy of... Oct 2016Lightweight artificial muscle fibers that can match the large tensile stroke of natural muscles have been elusive. In particular, low stroke, limited cycle life, and... (Review)
Review
Lightweight artificial muscle fibers that can match the large tensile stroke of natural muscles have been elusive. In particular, low stroke, limited cycle life, and inefficient energy conversion have combined with high cost and hysteretic performance to restrict practical use. In recent years, a new class of artificial muscles, based on highly twisted fibers, has emerged that can deliver more than 2,000 J/kg of specific work during muscle contraction, compared with just 40 J/kg for natural muscle. Thermally actuated muscles made from ordinary polymer fibers can deliver long-life, hysteresis-free tensile strokes of more than 30% and torsional actuation capable of spinning a paddle at speeds of more than 100,000 rpm. In this perspective, we explore the mechanisms and potential applications of present twisted fiber muscles and the future opportunities and challenges for developing twisted muscles having improved cycle rates, efficiencies, and functionality. We also demonstrate artificial muscle sewing threads and textiles and coiled structures that exhibit nearly unlimited actuation strokes. In addition to robotics and prosthetics, future applications include smart textiles that change breathability in response to temperature and moisture and window shutters that automatically open and close to conserve energy.
Topics: Biomimetic Materials; Mechanical Phenomena; Muscle Contraction; Muscles; Nanotubes, Carbon; Polymers; Tensile Strength; Textiles
PubMed: 27671626
DOI: 10.1073/pnas.1605273113 -
Redox Biology Aug 2020Endurance exercise training promotes numerous biochemical adaptations within skeletal muscle fibers culminating into a phenotype that is safeguarded against numerous... (Review)
Review
Endurance exercise training promotes numerous biochemical adaptations within skeletal muscle fibers culminating into a phenotype that is safeguarded against numerous perils including doxorubicin-induced myopathy and inactivity-induced muscle atrophy. This exercise-induced protection of skeletal muscle fibers is commonly termed "exercise preconditioning". This review will discuss the biochemical mechanisms responsible for exercise-induced protection of skeletal muscle fibers against these harmful events. The first segment of this report highlights the evidence that endurance exercise training provides cytoprotection to skeletal muscle fibers against several potentially damaging insults. The second and third sections of the review will discuss the cellular adaptations responsible for exercise-induced protection of skeletal muscle fibers against doxorubicin-provoked damage and inactivity-induced fiber atrophy, respectively. Importantly, we also identify gaps in our understanding of exercise preconditioning in hopes of stimulating future research.
Topics: Adaptation, Physiological; Exercise; Humans; Muscle Fibers, Skeletal; Muscle, Skeletal; Muscular Atrophy
PubMed: 32089451
DOI: 10.1016/j.redox.2020.101462