-
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 -
Pharmacological Research Oct 2021Skeletal muscle is a crucial tissue for movement, gestural assistance, metabolic homeostasis, and thermogenesis. It makes up approximately 40% of the total body weight... (Review)
Review
Skeletal muscle is a crucial tissue for movement, gestural assistance, metabolic homeostasis, and thermogenesis. It makes up approximately 40% of the total body weight and 50% of total protein. However, several pathological abnormalities (e.g., chronic diseases, cancer, long-term infection, aging) can induce an imbalance in skeletal muscle protein synthesis and degradation, which triggers muscle wasting and even leads to atrophy. Skeletal muscle atrophy is characterized by weakening, shrinking, and decreasing muscle mass and fiber cross-sectional area at the histological level. It manifests as a reduction in force production, easy fatigue and decreased exercise capability, along with a lower quality of life. Mechanistically, there are several pathophysiological processes involved in skeletal muscle atrophy, including oxidative stress and inflammation, which then activate signal transduction, such as the ubiquitin proteasome system, autophagy lysosome system, and mTOR. Considering the great economic and social burden that muscle atrophy can inflict, effective prevention and treatment strategies are essential but still limited. Exercise is widely acknowledged as the most effective therapy for skeletal muscle atrophy; unfortunately, it is not applicable for all patients. Several active substances for skeletal muscle atrophy have been discovered and evaluated in clinical trials, however, they have not been marketed to date. Knowledge is being gained on the underlying mechanisms, highlighting more promising treatment strategies in the future. In this paper, the mechanisms and treatment strategies for skeletal muscle atrophy are briefly reviewed.
Topics: Animals; Humans; Muscle, Skeletal; Muscular Atrophy
PubMed: 34389456
DOI: 10.1016/j.phrs.2021.105807 -
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 -
Nature Reviews. Disease Primers Oct 2023Traumatic muscle injury represents a collection of skeletal muscle pathologies caused by trauma to the muscle tissue and is defined as damage to the muscle tissue that... (Review)
Review
Traumatic muscle injury represents a collection of skeletal muscle pathologies caused by trauma to the muscle tissue and is defined as damage to the muscle tissue that can result in a functional deficit. Traumatic muscle injury can affect people across the lifespan and can result from high stresses and strains to skeletal muscle tissue, often due to muscle activation while the muscle is lengthening, resulting in indirect and non-contact muscle injuries (strains or ruptures), or from external impact, resulting in direct muscle injuries (contusion or laceration). At a microscopic level, muscle fibres can repair focal damage but must be completely regenerated after full myofibre necrosis. The diagnosis of muscle injury is based on patient history and physical examination. Imaging may be indicated to eliminate differential diagnoses. The management of muscle injury has changed within the past 5 years from initial rest, immobilization and (over)protection to early activation and progressive loading using an active approach. One challenge of muscle injury management is that numerous medical treatment options, such as medications and injections, are often used or proposed to try to accelerate muscle recovery despite very limited efficacy evidence. Another challenge is the prevention of muscle injury owing to the multifactorial and complex nature of this injury.
Topics: Humans; Muscle, Skeletal
PubMed: 37857686
DOI: 10.1038/s41572-023-00469-8 -
Nature Reviews. Molecular Cell Biology Mar 2022Skeletal muscle contains a designated population of adult stem cells, called satellite cells, which are generally quiescent. In homeostasis, satellite cells proliferate... (Review)
Review
Skeletal muscle contains a designated population of adult stem cells, called satellite cells, which are generally quiescent. In homeostasis, satellite cells proliferate only sporadically and usually by asymmetric cell division to replace myofibres damaged by daily activity and maintain the stem cell pool. However, satellite cells can also be robustly activated upon tissue injury, after which they undergo symmetric divisions to generate new stem cells and numerous proliferating myoblasts that later differentiate to muscle cells (myocytes) to rebuild the muscle fibre, thereby supporting skeletal muscle regeneration. Recent discoveries show that satellite cells have a great degree of population heterogeneity, and that their cell fate choices during the regeneration process are dictated by both intrinsic and extrinsic mechanisms. Extrinsic cues come largely from communication with the numerous distinct stromal cell types in their niche, creating a dynamically interactive microenvironment. This Review discusses the role and regulation of satellite cells in skeletal muscle homeostasis and regeneration. In particular, we highlight the cell-intrinsic control of quiescence versus activation, the importance of satellite cell-niche communication, and deregulation of these mechanisms associated with ageing. The increasing understanding of how satellite cells are regulated will help to advance muscle regeneration and rejuvenation therapies.
Topics: Cell Differentiation; Muscle, Skeletal; Satellite Cells, Skeletal Muscle; Stem Cells
PubMed: 34663964
DOI: 10.1038/s41580-021-00421-2 -
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 -
Neuropharmacology Oct 2021Endocrine mechanisms have been largely associated with metabolic control and tissue cross talk in mammals. Classically, myokines comprise a class of signaling proteins... (Review)
Review
Endocrine mechanisms have been largely associated with metabolic control and tissue cross talk in mammals. Classically, myokines comprise a class of signaling proteins released in the bloodstream by the skeletal muscle, which mediate physiological and metabolic responses in several tissues, including the brain. Recent exciting evidence suggests that myokines (e.g. cathepsin B, FNDC5/irisin, interleukin-6) act to control brain functions, including learning, memory, and mood, and may mediate the beneficial actions of physical exercise in the brain. However, the intricate mechanisms connecting peripherally released molecules to brain function are not fully understood. Accumulating findings further indicates that impaired skeletal muscle homeostasis impacts brain metabolism and physiology. Here we review recent findings that suggest that muscle-borne signals are essential for brain physiology and discuss perspectives on how these signals vary in response to exercise or muscle diseases. Understanding the complex interactions between skeletal muscle and brain may result in more effective therapeutic strategies to expand healthspan and to prevent brain disease. This article is part of the special Issue on 'Cross Talk between Periphery and the Brain'.
Topics: Animals; Brain; Brain Chemistry; Humans; Muscle, Skeletal; Signal Transduction
PubMed: 34363812
DOI: 10.1016/j.neuropharm.2021.108744 -
Cell and Tissue Research Aug 2019There is a current need for a therapy that can alleviate the social and economic burden that presents itself with debilitating and recurring musculoskeletal soft tissue... (Review)
Review
There is a current need for a therapy that can alleviate the social and economic burden that presents itself with debilitating and recurring musculoskeletal soft tissue injuries and disorders. Currently, several therapies are emerging and undergoing trials in animal models; these focus on the manipulation and administration of several growth factors implicated with healing. However, limitations include in vivo instability, reliance on biocompatible and robust carriers and restricted application procedures (local and direct). The aim of this paper is therefore to critically review the current literature surrounding the use of BPC 157, as a feasible therapy for healing and functional restoration of soft tissue damage, with a focus on tendon, ligament and skeletal muscle healing. Currently, all studies investigating BPC 157 have demonstrated consistently positive and prompt healing effects for various injury types, both traumatic and systemic and for a plethora of soft tissues. However, to date, the majority of studies have been performed on small rodent models and the efficacy of BPC 157 is yet to be confirmed in humans. Further, over the past two decades, only a handful of research groups have performed in-depth studies regarding this peptide. Despite this, it is apparent that BPC 157 has huge potential and following further development has promise as a therapy to conservatively treat or aid recovery in hypovascular and hypocellular soft tissues such as tendon and ligaments. Moreover, skeletal muscle injury models have suggested a beneficial effect not only for disturbances that occur as a result of direct trauma but also for systemic insults including hyperkalamia and hypermagnesia. Promisingly, there are few studies reporting any adverse reactions to the administration of BPC 157, although there is still a need to understand the precise healing mechanisms for this therapy to achieve clinical realisation.
Topics: Animals; Humans; Ligaments; Muscle, Skeletal; Peptide Fragments; Proteins; Tendon Injuries; Wound Healing
PubMed: 30915550
DOI: 10.1007/s00441-019-03016-8 -
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