scholarly journals Isometric resistance training increases strength and alters histopathology of dystrophin-deficient mouse skeletal muscle

2019 ◽  
Vol 126 (2) ◽  
pp. 363-375 ◽  
Author(s):  
Angus Lindsay ◽  
Alexie A. Larson ◽  
Mayank Verma ◽  
James M. Ervasti ◽  
Dawn A. Lowe
Keyword(s):  
Skeletal Muscle ◽  
Muscular Dystrophy ◽  
Muscle Strength ◽  
Exercise Training ◽  
Satellite Cells ◽  
Eccentric Contraction ◽  
Deficient Mouse ◽  
Isometric Training ◽  
Isometric Torque ◽  
Edl Muscle

Mutation to the dystrophin gene causes skeletal muscle weakness in patients with Duchenne muscular dystrophy (DMD) or Becker muscular dystrophy (BMD). Deliberation continues regarding implications of prescribing exercise for these patients. The purpose of this study was to determine whether isometric resistance exercise (~10 tetanic contractions/session) improves skeletal muscle strength and histopathology in the mdx mouse model of DMD. Three isometric training sessions increased in vivo isometric torque (22%) and contractility rates (54%) of anterior crural muscles of mdx mice. Mice expressing a BMD-causing missense mutated dystrophin on the mdx background showed comparable increases in torque (22%), while wild-type mice showed less change (11%). Increases in muscle function occurred within 1 h and peaked 3 days posttraining; however, the adaptation was lost after 7 days unless retrained. Six isometric training sessions over 4 wk caused increased isometric torque (28%) and contractility rates (22–28%), reduced fibrosis, as well as greater uniformity of fiber cross-sectional areas, fewer embryonic myosin heavy-chain-positive fibers, and more satellite cells in tibialis anterior muscle compared with the contralateral untrained muscle. Ex vivo functional analysis of isolated extensor digitorum longus (EDL) muscle from the trained hindlimb revealed greater absolute isometric force, lower passive stiffness, and a lower susceptibility to eccentric contraction-induced force loss compared with untrained EDL muscle. Overall, these data support the concept that exercise training in the form of isometric tetanic contractions can improve contractile function of dystrophin-deficient muscle, indicating a potential role for enhancing muscle strength in patients with DMD and BMD. NEW & NOTEWORTHY We focused on adaptive responses of dystrophin-deficient mouse skeletal muscle to isometric contraction training and report that in the absence of dystrophin (or in the presence of a mutated dystrophin), strength and muscle histopathology are improved. Results suggest that the strength gains are associated with fiber hypertrophy, reduced fibrosis, increased number of satellite cells, and blunted eccentric contraction-induced force loss in vitro. Importantly, there was no indication that the isometric exercise training was deleterious to dystrophin-deficient muscle.

scholarly journals Cellular senescence-mediated exacerbation of Duchenne muscular dystrophy

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Hidetoshi Sugihara ◽  
Naomi Teramoto ◽  
Katsuyuki Nakamura ◽  
Takanori Shiga ◽  
Taku Shirakawa ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Body Weight ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Muscle Strength ◽  
Progenitor Cells ◽  
Satellite Cells ◽  
Muscle Regeneration ◽  
Mesenchymal Progenitor Cells

Abstract Duchenne muscular dystrophy (DMD) is a progressive disease characterised by chronic muscle degeneration and inflammation. Our previously established DMD model rats (DMD rats) have a more severe disease phenotype than the broadly used mouse model. We aimed to investigate the role of senescence in DMD using DMD rats and patients. Senescence was induced in satellite cells and mesenchymal progenitor cells, owing to the increased expression of CDKN2A, p16- and p19-encoding gene. Genetic ablation of p16 in DMD rats dramatically restored body weight and muscle strength. Histological analysis showed a reduction of fibrotic and adipose tissues invading skeletal muscle, with increased muscle regeneration. Senolytic drug ABT263 prevented loss of body weight and muscle strength, and increased muscle regeneration in rats even at 8 months—the late stage of DMD. Moreover, senescence markers were highly expressed in the skeletal muscle of DMD patients. In situ hybridization of CDKN2A confirmed the expression of it in satellite cells and mesenchymal progenitor cells in patients with DMD. Collectively, these data provide new insights into the integral role of senescence in DMD progression.

scholarly journals Skeletal Muscle Adaptations to Exercise Training in Young and Aged Horses

2021 ◽  
Vol 2 ◽  
Author(s):  
Christine M. Latham ◽  
Randi N. Owen ◽  
Emily C. Dickson ◽  
Chloey P. Guy ◽  
Sarah H. White-Springer
Keyword(s):  
Skeletal Muscle ◽  
Electron Transfer ◽  
Exercise Training ◽  
Satellite Cells ◽  
Oxidative Capacity ◽  
System Capacity ◽  
Transfer System ◽  
Type Ii ◽  
Electron Transfer System ◽  
Young Horses

In aged humans, low-intensity exercise increases mitochondrial density, function and oxidative capacity, decreases the prevalence of hybrid fibers, and increases lean muscle mass, but these adaptations have not been studied in aged horses. Effects of age and exercise training on muscle fiber type and size, satellite cell abundance, and mitochondrial volume density (citrate synthase activity; CS), function (cytochrome c oxidase activity; CCO), and integrative (per mg tissue) and intrinsic (per unit CS) oxidative capacities were evaluated in skeletal muscle from aged (n = 9; 22 ± 5 yr) and yearling (n = 8; 9.7 ± 0.7 mo) horses. Muscle was collected from the gluteus medius (GM) and triceps brachii at wk 0, 8, and 12 of exercise training. Data were analyzed using linear models with age, training, muscle, and all interactions as fixed effects. At wk 0, aged horses exhibited a lower percentage of type IIx (p = 0.0006) and greater percentage of hybrid IIa/x fibers (p = 0.002) in the GM, less satellite cells per type II fiber (p = 0.03), lesser integrative and intrinsic (p≤ 0.04) CCO activities, lesser integrative oxidative phosphorylation capacity with complex I (PCI; p = 0.02) and maximal electron transfer system capacity (ECI+II; p = 0.06), and greater intrinsic PCI, ECI+II, and electron transfer system capacity with complex II (ECII; p≤ 0.05) than young horses. The percentage of type IIx fibers increased (p < 0.0001) and of type IIa/x fibers decreased (p = 0.001) in the GM, and the number of satellite cells per type II fiber increased (p = 0.0006) in aged horses following exercise training. Conversely, the percentage of type IIa/x fibers increased (p ≤ 0.01) and of type IIx fibers decreased (p ≤ 0.002) in young horses. Integrative maximal oxidative capacity (p ≤ 0.02), ECI+II (p ≤ 0.07), and ECII (p = 0.0003) increased for both age groups from wk 0 to 12. Following exercise training, aged horses had a greater percentage of IIx (p ≤ 0.002) and lesser percentage of IIa/x fibers (p ≤ 0.07), and more satellite cells per type II fiber (p = 0.08) than young horses, but sustained lesser integrative and intrinsic CCO activities (p≤ 0.04) and greater intrinsic PCI, ECI+II, and ECII (p≤ 0.05). Exercise improved mitochondrial measures in young and aged horses; however, aged horses showed impaired mitochondrial function and differences in adaptation to exercise training.

Exercise training increases skeletal muscle strength independent of hypertrophy in older adults aged 75 years and older

2019 ◽  
Vol 19 (3) ◽  
pp. 265-270 ◽  
Author(s):  
Hojun Lee ◽  
In-Gyu Kim ◽  
Changsu Sung ◽  
Tae-Bong Jeon ◽  
Kibum Cho ◽  
...  
Keyword(s):  
Older Adults ◽  
Skeletal Muscle ◽  
Muscle Strength ◽  
Exercise Training ◽  
Skeletal Muscle Strength

scholarly journals Histone Modification: A Mechanism for Regulating Skeletal Muscle Characteristics and Adaptive Changes

2021 ◽  
Vol 11 (9) ◽  
pp. 3905
Author(s):  
Fuminori Kawano
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Histone Modification ◽  
Histone Modifications ◽  
Satellite Cells ◽  
Skeletal Muscles ◽  
Critical Role ◽  
Cell Lineage ◽  
Muscle Adaptation ◽  
Adaptive Changes

Epigenetics is getting increased attention in the analysis of skeletal muscle adaptation to physiological stimuli. In this review, histone modifications in skeletal muscles and their role in the regulation of muscle characteristics and adaptive changes are highlighted. The distribution of active histone modifications, such as H3K4me3 and H3 acetylation, largely differs between fast- and slow-twitch muscles. It is also indicated that the transcriptional activity in response to exercise differs in these muscle types. Histone turnover activated by exercise training leads to loosening of nucleosomes, which drastically enhances gene responsiveness to exercise, indicating that the exercise training transforms the chromatin structure to an active status. Furthermore, histone modifications play a critical role in preserving the stem cell lineage in skeletal muscle. Lack of lysine-specific demethylase 1 in satellite cells promotes the differentiation into brown adipocytes during muscle regeneration after injury. H4K20me2, which promotes the formation of heterochromatin, is necessary to repress MyoD expression in the satellite cells. These observations indicate that histone modification is a platform that characterizes skeletal muscles and may be one of the factors regulating the range of adaptive changes in these muscles.

scholarly journals Effects of Exercise Intervention on Peripheral Skeletal Muscle in Stable Patients With COPD: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 8 ◽  
Author(s):  
Peijun Li ◽  
Jian Li ◽  
Yingqi Wang ◽  
Jun Xia ◽  
Xiaodan Liu
Keyword(s):  
Skeletal Muscle ◽  
Muscle Strength ◽  
Exercise Training ◽  
Resistance Exercise ◽  
Exercise Capacity ◽  
Meta Analysis ◽  
Exercise Interventions ◽  
Randomized Controlled ◽  
Copd Patients ◽  
Training Modalities

Objectives: Peripheral skeletal muscle dysfunction is an important extrapulmonary manifestation of chronic obstructive pulmonary disease (COPD) that can be counteracted by exercise training. This study aimed to review the effect of three major exercise training modalities, which are used in pulmonary rehabilitation to improve on skeletal muscle mass, function, and exercise capacity in COPD.Methods: PubMed, Embase, EBSCO, Web of Science, and the PEDro database were searched on April 25, 2020. Only randomized controlled studies published in English evaluating the effects of exercise interventions on peripheral skeletal muscle mass, strength, and exercise capacity in stable COPD patients were included. The quality of included studies was evaluated using the PEDro scale. The mean difference (MD) or the standardized mean difference (SMD) with 95% CI was calculated to summarize the results. Subgroup meta-analysis was used to investigate the effects of different exercise training modalities and different outcome measures. The Grading of Recommendations Assessment, Development, and Evaluation guidelines were used to rate evidence quality.Results: A total of 30 randomized controlled trials involving 1,317 participants were included. Data from trials investigating endurance exercise (EE), resistance exercise (RE), and combined aerobic and resistance exercise (CE) were pooled into a meta-analysis, and the differences compared with the non-exercising COPD control were improvement in the muscle strength and exercise capacity in stable COPD patients. Subgroup meta-analysis for different exercise training modalities showed that RE significantly improved muscle strength (SMD = 0.6, 95% CI 0.35–0.84, I2 = 61%), EE and CE significantly increased VO2peak (EE: MD = 3.5, 95% CI 1.1–5.91, I2 = 92%; CE: MD = 1.66, 95% CI 0.22–3.1, I2 = 1%). Subgroup meta-analysis for different outcome measures showed that only isotonic strength was improved after exercise interventions (SMD = 0.89, 95% CI 0.51–1.26, I2 = 71%).Conclusion: Moderate evidence supports that exercise training in stable COPD patients has meaningful and beneficial effects on peripheral skeletal muscle strength and exercise capacity. Peripheral skeletal muscle shows a higher response to RE, and the isotonic test is relatively sensitive in reflecting muscle strength changes. The proportion of aerobic and resistance exercise components in a combined exercise program still needs exploration.Systematic Review Registration: The review was registered with the PROSPERO: (The website is https://www.crd.york.ac.uk/PROSPERO/, and the ID is CRD42020164868).

scholarly journals Measuring skeletal muscle strength and endurance, from bench to bedside

2008 ◽  
Vol 31 (5) ◽  
pp. 307 ◽  
Author(s):  
Didier Saey ◽  
Thierry Troosters
Keyword(s):  
Skeletal Muscle ◽  
Muscle Strength ◽  
Exercise Training ◽  
Muscle Weakness ◽  
Muscle Function ◽  
Muscle Endurance ◽  
Muscle Dysfunction ◽  
Skeletal Muscle Function ◽  
Peripheral Muscle ◽  
Skeletal Muscle Strength

Peripheral muscle dysfunction is a recognized and important systemic consequence of many chronic diseases. Peripheral muscle weakness is associated with excess utilization of health care recourses, morbidity and /or mortality in patients with COPD, congestive heart failure, liver and frail elderly. In the latter group, muscle weakness was associated with significant increase in falling and falling related injury. Exercise training does enhance skeletal muscle function and exercise performance. In addition, patients who start a training program with impaired skeletal muscle function may be more likely to respond adequately to an exercise training program. It is beyond the scope of the present review to discuss in detail the factors that may contribute to muscle dysfunction in chronic conditions. Clearly, muscle weakness is multi-factorial. Factors associated with skeletal muscle force are general factors (such as age, body weight, sex), disease related factors (such as inactivity) and disease specific factors (for example in COPD drug treatment, i.e. corticosteroid treatment, inflammation, oxidative stress and hypoxia have been shown to contribute to muscle dysfunction). This review will focus on the different ways to assess skeletal muscle function in patients with chronic disease. More specifically, techniques to assess skeletal muscle strength, skeletal muscle endurance and skeletal muscle fatigue will be discussed. For the American College of Sport Medicine (ACSM) not only muscle strength but also muscle endurance are health- related fitness components. Loss in one of these muscle characteristics results in impaired muscle. Muscle function tests are very specific to the muscle group tested, the type of contraction, the velocity of muscle motion, the type of equipment and the joint range of motion. Results of any test are specific to the procedures used. Individuals should participate in familiarization sessions with the equipment, and adhere to a specific protocol in order to obtain a true and reliable score. A change in one’s muscular fitness over time can be based on the absolute value of the external force (Newton (N)), but when comparisons are made between individuals, the values should be expressed as relative values (percentage of a predicted normal value). In both cases, caution must be taken in the interpretation of the result because the norms may not include a representative sample of the individual being measured, a standardized protocol may be absent, or the exact test being used may differ.

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