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Medicine and Science in Sports and... Sep 2022Skeletal muscle plays a critical role in physical function and metabolic health. Muscle is a highly adaptable tissue that responds to resistance exercise (RE; loading)... (Review)
Review
Skeletal muscle plays a critical role in physical function and metabolic health. Muscle is a highly adaptable tissue that responds to resistance exercise (RE; loading) by hypertrophying, or during muscle disuse, RE mitigates muscle loss. Resistance exercise training (RET)-induced skeletal muscle hypertrophy is a product of external (e.g., RE programming, diet, some supplements) and internal variables (e.g., mechanotransduction, ribosomes, gene expression, satellite cells activity). RE is undeniably the most potent nonpharmacological external variable to stimulate the activation/suppression of internal variables linked to muscular hypertrophy or countering disuse-induced muscle loss. Here, we posit that despite considerable research on the impact of external variables on RET and hypertrophy, internal variables (i.e., inherent skeletal muscle biology) are dominant in regulating the extent of hypertrophy in response to external stimuli. Thus, identifying the key internal skeletal muscle-derived variables that mediate the translation of external RE variables will be pivotal to determining the most effective strategies for skeletal muscle hypertrophy in healthy persons. Such work will aid in enhancing function in clinical populations, slowing functional decline, and promoting physical mobility. We provide up-to-date, evidence-based perspectives of the mechanisms regulating RET-induced skeletal muscle hypertrophy.
Topics: Exercise; Humans; Hypertrophy; Mechanotransduction, Cellular; Muscle, Skeletal; Resistance Training
PubMed: 35389932
DOI: 10.1249/MSS.0000000000002929 -
Wiley Interdisciplinary Reviews.... Jan 2020Decades of research in skeletal muscle physiology have provided multiscale insights into the structural and functional complexity of this important anatomical tissue,... (Review)
Review
Decades of research in skeletal muscle physiology have provided multiscale insights into the structural and functional complexity of this important anatomical tissue, designed to accomplish the task of generating contraction, force and movement. Skeletal muscle can be viewed as a biomechanical device with various interacting components including the autonomic nerves for impulse transmission, vasculature for efficient oxygenation, and embedded regulatory and metabolic machinery for maintaining cellular homeostasis. The "omics" revolution has propelled a new era in muscle research, allowing us to discern minute details of molecular cross-talk required for effective coordination between the myriad interacting components for efficient muscle function. The objective of this review is to provide a systems-level, comprehensive mapping the molecular mechanisms underlying skeletal muscle structure and function, in health and disease. We begin this review with a focus on molecular mechanisms underlying muscle tissue development (myogenesis), with an emphasis on satellite cells and muscle regeneration. We next review the molecular structure and mechanisms underlying the many structural components of the muscle: neuromuscular junction, sarcomere, cytoskeleton, extracellular matrix, and vasculature surrounding muscle. We highlight aberrant molecular mechanisms and their possible clinical or pathophysiological relevance. We particularly emphasize the impact of environmental stressors (inflammation and oxidative stress) in contributing to muscle pathophysiology including atrophy, hypertrophy, and fibrosis. This article is categorized under: Physiology > Mammalian Physiology in Health and Disease Developmental Biology > Developmental Processes in Health and Disease Models of Systems Properties and Processes > Cellular Models.
Topics: Animals; Biophysical Phenomena; Extracellular Matrix; Humans; Models, Biological; Muscle Contraction; Muscle, Skeletal; Muscular Diseases; Neuromuscular Junction; Satellite Cells, Skeletal Muscle; Synapses
PubMed: 31407867
DOI: 10.1002/wsbm.1462 -
American Journal of Physiology. Cell... Jun 2023Skeletal muscle memory is an exciting phenomenon gaining significant traction across several scientific communities, among exercise practitioners, and the public.... (Review)
Review
Skeletal muscle memory is an exciting phenomenon gaining significant traction across several scientific communities, among exercise practitioners, and the public. Research has demonstrated that skeletal muscle tissue can be "primed" by earlier positive encounters with exercise training that can enhance adaptation to later retraining, even following significant periods of exercise cessation or detraining. This review will describe and discuss the most recent research investigating the underlying mechanisms of skeletal muscle memory: ) "cellular" muscle memory and, ) "epigenetic" muscle memory, as well as emerging evidence of how these theories may work in synergy. We will discuss both "positive" and "negative" muscle memory and highlight the importance of investigating muscle memory for optimizing exercise interventions and training programs as well as the development of therapeutic strategies for counteracting muscle wasting conditions and age-related muscle loss. Finally, important directions emerging in the field will be highlighted to advance the next generation of studies in skeletal muscle memory research into the future.
Topics: Humans; Muscle, Skeletal; Exercise; Muscular Atrophy; Adaptation, Physiological; Muscle Cells
PubMed: 37154489
DOI: 10.1152/ajpcell.00099.2023 -
Frontiers in Immunology 2023Responding to tissue injury, skeletal muscles undergo the tissue destruction and reconstruction accompanied with inflammation. The immune system recognizes the molecules... (Review)
Review
Responding to tissue injury, skeletal muscles undergo the tissue destruction and reconstruction accompanied with inflammation. The immune system recognizes the molecules released from or exposed on the damaged tissue. In the local minor tissue damage, tissue-resident macrophages sequester pro-inflammatory debris to prevent initiation of inflammation. In most cases of the skeletal muscle injury, however, a cascade of inflammation will be initiated through activation of local macrophages and mast cells and recruitment of immune cells from blood circulation to the injured site by recongnization of damage-associated molecular patterns (DAMPs) and activated complement system. During the inflammation, macrophages and neutrophils scavenge the tissue debris to release inflammatory cytokines and the latter stimulates myoblast fusion and vascularization to promote injured muscle repair. On the other hand, an abundance of released inflammatory cytokines and chemokines causes the profound hyper-inflammation and mobilization of immune cells to trigger a vicious cycle and lead to the cytokine storm. The cytokine storm results in the elevation of cytolytic and cytotoxic molecules and reactive oxygen species (ROS) in the damaged muscle to aggravates the tissue injury, including the healthy bystander tissue. Severe inflammation in the skeletal muscle can lead to rhabdomyolysis and cause sepsis-like systemic inflammation response syndrome (SIRS) and remote organ damage. Therefore, understanding more details on the involvement of inflammatory factors and immune cells in the skeletal muscle damage and repair can provide the new precise therapeutic strategies, including attenuation of the muscle damage and promotion of the muscle repair.
Topics: Humans; Cytokine Release Syndrome; Inflammation; Muscle, Skeletal; Systemic Inflammatory Response Syndrome; Cytokines
PubMed: 36776867
DOI: 10.3389/fimmu.2023.1133355 -
Mechanisms of Ageing and Development Dec 2021Cellular senescence is a state of cell cycle arrest induced by several forms of metabolic stress. Senescent cells accumulate with advancing age and have a distinctive... (Review)
Review
Cellular senescence is a state of cell cycle arrest induced by several forms of metabolic stress. Senescent cells accumulate with advancing age and have a distinctive phenotype, characterized by profound chromatin alterations and a robust senescence-associated secretory phenotype (SASP) that exerts negative effects on tissue health, both locally and systemically. In preclinical models, pharmacological agents that eliminate senescent cells (senotherapeutics) restore health and youthful properties in multiple tissues. To date, however, very little is understood about the vulnerability of terminally-differentiated skeletal muscle fibers and the resident mononuclear cells that populate the interstitial microenvironment of skeletal muscle to senescence, and their contribution to the onset and progression of skeletal muscle loss and dysfunction with aging. Scientific advances in these areas have the potential to highlight new therapeutic approaches to optimize late-life muscle health. To this end, this review highlights the current evidence and the key questions that need to be addressed to advance the field's understanding of cellular senescence as a mediator of skeletal muscle aging and the potential for emerging senescent cell-targeting therapies to counter age-related deficits in muscle mass, strength, and function. This article is part of the Special Issue - Senolytics - Edited by Joao Passos and Diana Jurk.
Topics: Cellular Senescence; Humans; Muscle, Skeletal; Sarcopenia; Senescence-Associated Secretory Phenotype; Senotherapeutics
PubMed: 34742751
DOI: 10.1016/j.mad.2021.111595 -
Open Biology Dec 2021Skeletal muscle possesses a remarkable regenerative capacity that relies on the activity of muscle stem cells, also known as satellite cells. The presence of... (Review)
Review
Skeletal muscle possesses a remarkable regenerative capacity that relies on the activity of muscle stem cells, also known as satellite cells. The presence of non-myogenic cells also plays a key role in the coordination of skeletal muscle regeneration. Particularly, fibro-adipogenic progenitors (FAPs) emerged as master regulators of muscle stem cell function and skeletal muscle regeneration. This population of muscle resident mesenchymal stromal cells has been initially characterized based on its bi-potent ability to differentiate into fibroblasts or adipocytes. New technologies such as single-cell RNAseq revealed the cellular heterogeneity of FAPs and their complex regulatory network during muscle regeneration. In acute injury, FAPs rapidly enter the cell cycle and secrete trophic factors that support the myogenic activity of muscle stem cells. Conversely, deregulation of FAP cell activity is associated with the accumulation of fibrofatty tissue in pathological conditions such as muscular dystrophies and ageing. Considering their central role in skeletal muscle pathophysiology, the regulatory mechanisms of FAPs and their cellular and molecular crosstalk with muscle stem cells are highly investigated in the field. In this review, we summarize the current knowledge on FAP cell characteristics, heterogeneity and the cellular crosstalk during skeletal muscle homeostasis and regeneration. We further describe their role in muscular disorders, as well as different therapeutic strategies targeting these cells to restore muscle regeneration.
Topics: Adipogenesis; Animals; Cell Differentiation; Gene Regulatory Networks; Homeostasis; Humans; Mesenchymal Stem Cells; Muscle, Skeletal; Regeneration; Sequence Analysis, RNA; Single-Cell Analysis
PubMed: 34875199
DOI: 10.1098/rsob.210110 -
Nutrients Aug 2019The active form of vitamin D (calcitriol) exerts its biological effects by binding to nuclear vitamin D receptors (VDRs), which are found in most human extraskeletal... (Review)
Review
The active form of vitamin D (calcitriol) exerts its biological effects by binding to nuclear vitamin D receptors (VDRs), which are found in most human extraskeletal cells, including skeletal muscles. Vitamin D deficiency may cause deficits in strength, and lead to fatty degeneration of type II muscle fibers, which has been found to negatively correlate with physical performance. Vitamin D supplementation has been shown to improve vitamin D status and can positively affect skeletal muscles. The purpose of this study is to summarize the current evidence of the relationship between vitamin D, skeletal muscle function and physical performance in athletes. Additionally, we will discuss the effect of vitamin D supplementation on athletic performance in players. Further studies are necessary to fully characterize the underlying mechanisms of calcitriol action in the human skeletal muscle tissue, and to understand how these actions impact the athletic performance in athletes.
Topics: Animals; Athletes; Athletic Performance; Calcitriol; Dietary Supplements; Humans; Muscle Contraction; Muscle Strength; Muscle, Skeletal; Nutritional Status; Receptors, Calcitriol; Signal Transduction; Vitamin D Deficiency
PubMed: 31382666
DOI: 10.3390/nu11081800 -
Nutrients Mar 2020Assessment of a low skeletal muscle mass (SM) is important for diagnosis of ageing and disease-associated sarcopenia and is hindered by heterogeneous methods and... (Review)
Review
Assessment of a low skeletal muscle mass (SM) is important for diagnosis of ageing and disease-associated sarcopenia and is hindered by heterogeneous methods and terminologies that lead to differences in diagnostic criteria among studies and even among consensus definitions. The aim of this review was to analyze and summarize previously published cut-offs for SM applied in clinical and research settings and to facilitate comparison of results between studies. Multiple published reference values for discrepant parameters of SM were identified from 64 studies and the underlying methodological assumptions and limitations are compared including different concepts for normalization of SM for body size and fat mass (FM). Single computed tomography or magnetic resonance imaging images and appendicular lean soft tissue by dual X-ray absorptiometry (DXA) or bioelectrical impedance analysis (BIA) are taken as a valid substitute of total SM because they show a high correlation with results from whole body imaging in cross-sectional and longitudinal analyses. However, the random error of these methods limits the applicability of these substitutes in the assessment of individual cases and together with the systematic error limits the accurate detection of changes in SM. Adverse effects of obesity on muscle quality and function may lead to an underestimation of sarcopenia in obesity and may justify normalization of SM for FM. In conclusion, results for SM can only be compared with reference values using the same method, BIA- or DXA-device and an appropriate reference population. Limitations of proxies for total SM as well as normalization of SM for FM are important content-related issues that need to be considered in longitudinal studies, populations with obesity or older subjects.
Topics: Body Mass Index; Humans; Muscle, Skeletal; Obesity; Reference Values; Sarcopenia
PubMed: 32178373
DOI: 10.3390/nu12030755 -
Journal of Cachexia, Sarcopenia and... Dec 2022Human pluripotent stem cell-derived muscle models show great potential for translational research. Here, we describe developmentally inspired methods for the derivation...
BACKGROUND
Human pluripotent stem cell-derived muscle models show great potential for translational research. Here, we describe developmentally inspired methods for the derivation of skeletal muscle cells and their utility in skeletal muscle tissue engineering with the aim to model skeletal muscle regeneration and dystrophy in vitro.
METHODS
Key steps include the directed differentiation of human pluripotent stem cells to embryonic muscle progenitors followed by primary and secondary foetal myogenesis into three-dimensional muscle. To simulate Duchenne muscular dystrophy (DMD), a patient-specific induced pluripotent stem cell line was compared to a CRISPR/Cas9-edited isogenic control line.
RESULTS
The established skeletal muscle differentiation protocol robustly and faithfully recapitulates critical steps of embryonic myogenesis in two-dimensional and three-dimensional cultures, resulting in functional human skeletal muscle organoids (SMOs) and engineered skeletal muscles (ESMs) with a regeneration-competent satellite-like cell pool. Tissue-engineered muscle exhibits organotypic maturation and function (up to 5.7 ± 0.5 mN tetanic twitch tension at 100 Hz in ESM). Contractile performance could be further enhanced by timed thyroid hormone treatment, increasing the speed of contraction (time to peak contraction) as well as relaxation (time to 50% relaxation) of single twitches from 107 ± 2 to 75 ± 4 ms (P < 0.05) and from 146 ± 6 to 100 ± 6 ms (P < 0.05), respectively. Satellite-like cells could be documented as largely quiescent PAX7 cells (75 ± 6% Ki67 ) located adjacent to muscle fibres confined under a laminin-containing basal membrane. Activation of the engineered satellite-like cell niche was documented in a cardiotoxin injury model with marked recovery of contractility to 57 ± 8% of the pre-injury force 21 days post-injury (P < 0.05 compared to Day 2 post-injury), which was completely blocked by preceding irradiation. Absence of dystrophin in DMD ESM caused a marked reduction of contractile force (-35 ± 7%, P < 0.05) and impaired expression of fast myosin isoforms resulting in prolonged contraction (175 ± 14 ms, P < 0.05 vs. gene-edited control) and relaxation (238 ± 22 ms, P < 0.05 vs. gene-edited control) times. Restoration of dystrophin levels by gene editing rescued the DMD phenotype in ESM.
CONCLUSIONS
We introduce human muscle models with canonical properties of bona fide skeletal muscle in vivo to study muscle development, maturation, disease and repair.
Topics: Humans; Muscular Dystrophy, Duchenne; Muscle, Skeletal; Muscle Development; Satellite Cells, Skeletal Muscle; Muscle Fibers, Skeletal
PubMed: 36254806
DOI: 10.1002/jcsm.13094 -
Biomedicine & Pharmacotherapy =... Jun 2023Skeletal muscle is the most extensive tissue in mammals, and they perform several functions; it is derived from paraxial mesodermal somites and undergoes hyperplasia and... (Review)
Review
Skeletal muscle is the most extensive tissue in mammals, and they perform several functions; it is derived from paraxial mesodermal somites and undergoes hyperplasia and hypertrophy to form multinucleated, contractile, and functional muscle fibers. Skeletal muscle is a complex heterogeneous tissue composed of various cell types that establish communication strategies to exchange biological information; therefore, characterizing the cellular heterogeneity and transcriptional signatures of skeletal muscle is central to understanding its ontogeny's details. Studies of skeletal myogenesis have focused primarily on myogenic cells' proliferation, differentiation, migration, and fusion and ignored the intricate network of cells with specific biological functions. The rapid development of single-cell sequencing technology has recently enabled the exploration of skeletal muscle cell types and molecular events during development. This review summarizes the progress in single-cell RNA sequencing and its applications in skeletal myogenesis, which will provide insights into skeletal muscle pathophysiology.
Topics: Animals; Muscle, Skeletal; Muscle Fibers, Skeletal; Cell Differentiation; Mammals; Muscle Development; Developmental Biology; Sequence Analysis, RNA
PubMed: 37003036
DOI: 10.1016/j.biopha.2023.114631