Muscle Plasticity Research Articles

Prolonged mechanical muscle loading increases mechanosensor gene and protein levels and causes a moderate fast-to-slow fiber type switch in mice.

Mechanosensing and subsequent mechanotransduction are indispensable for muscle plasticity. Nevertheless, a scarcity of literature exists regarding an all-encompassing understanding of the muscle mechanosensing machinery's response to prolonged loading, especially in conditions that resemble a natural physiological state of skeletal muscle. This study aimed to comprehensively explore the effects of prolonged mechanical loading on mechanosensitive components, skeletal muscle characteristics, and metabolism-related gene clusters. Twenty male C57BL/6J mice were randomly divided into two groups: control and prolonged mechanical loading. To induce prolonged mechanical loading on the triceps brachii (TRI) and biceps brachii (BIC) muscles, a 14-day period of tail suspension was implemented. In TRI only, prolonged mechanical loading caused a mild fast-to-slow fiber type shift together with increased mechanosensor gene and protein levels. It also increased transcription factors associated with slow muscle fibers while decreasing those related to fast-type muscle gene expression. Succinate dehydrogenase activity, a marker of muscle oxidative capacity, and genes involved in oxidative and mitochondrial turnover increased, whereas glycolytic-related genes decreased. Moreover, prolonged mechanical loading stimulated markers of muscle protein synthesis. Taken together, our data show a collective muscle-specific increase in mechanosensor gene and protein levels upon a period of prolonged mechanical loading in conditions that reflect a more natural physiological state of skeletal muscle in mice. We provide additional proof-of-concept that prolonged tail suspension-induced loading of the forelimbs triggers a muscle-specific fast-to-slow fiber type switch, and this coincides with increased protein synthesis-related signaling.NEW & NOTEWORTHY This study provides a comprehensive overview of the effects of prolonged loading on mechanosensitive components in conditions that better reflect the natural physiological state of skeletal muscle. Although the muscle mechanosensing machinery has been widely acknowledged for its responsiveness to altered loading, an inclusive understanding of its response to prolonged loading remains scarce. Our results show a fast-to-slow fiber type shift and an upregulation of mechanosensor gene and protein levels following prolonged loading.

Транскрипционные факторы в скелетной мышце человека, ассоциированные с однократным и регулярными силовыми упражнениями

Skeletal muscle plasticity is the ability to change morphofunctional properties in response to changes in contractile activity. Strength training increases the size of muscle fibers and maximum strength with the activation of protein synthesis. Regulation of these changes at the gene level has not been investigated properly. This study aimed to identify transcription factors associated with changes in the transcriptome of the human skeletal muscle in the context of single and regular strength exercises. We assessed changes in the transcriptomic profile of m. vastus lateralis of 10 young men (mean age 23 (20.8 - 25.9) years) before and after 12-week leg extensor muscles strength training course, as well as before, 8 and 24 hours after a single exercise. Transcriptomic profiling involved RNA sequencing, search for binding motifs and the associated transcription factors. Bioinformatic methods of statistics, FastQC, GraphPad Prizm 8, DAVID, R enabled analysis of the data acquired. The strength training course resulted in the enrichment of the functional groups of genes "secreted proteins", "extracellular matrix" and "basal membrane" (p < 0.05). Transcriptomic responses and the associated transcription factors differed 8 and 24 hours after a single session as well as after regular training sessions. Transcription factors involved in adjustment to regular and one-time loads participate in myogenesis, angiogenesis, regulation of fiber phenotype, proteostasis and other processes. Thus, regulation of gene expression during adjustment to the resistance training loads is a complex process that involves many transcription factors with different functions. Investigation of the role played by these factors in the context of adjustment to exercising is a potentially rewarding task.

Muscle growth and plasticity in teleost fish: the significance of evolutionarily diverse sarcomeric proteins

Muscle growth and plasticity in teleost fish: the significance of evolutionarily diverse sarcomeric proteins

Characterization of myosin heavy chain (MYH) genes and their differential expression in white and red muscles of Chinese perch, Siniperca chuatsi

Fish skeletal muscle is composed of two anatomically and functionally different fiber layers, white or fast and red or slow muscles. Myosin, the major structural protein of fish skeletal muscle, contains multiple myosin heavy chain (MYH) isoforms involved in the high plasticity of muscle in response to varying functional demands and/or environmental changes. In this study, we comparatively assayed the cellular and ultrastructural feature of white and red skeletal muscles. Then, a total of 28 class II myosin heavy chain genes were identified in by searching the Chinese perch genome database. Among them, 14 genes code for the fast-muscle-type myosin heavy chain, and 7 genes code for the slow-muscle-type myosin heavy chain. Further, the different isoform gene structures, function domains, phylogenetic relations, and muscle-fiber type-specific expression were characterized. This is the first systematic work on the molecular characterization of class II myosin heavy chain isoforms and the differential analysis of their expression in red and white muscle tissues in Chinese perch Siniperca chuatsi. Our work provided valuable information for a better understanding of myh genes and their molecular characteristics, and the correlations of multiple myosin isoforms with potential functions in response to varying functional demands and/or environmental changes.

Smooth Muscle Heterogeneity and Plasticity in Health and Aortic Aneurysmal Disease.

Vascular smooth muscle cells (VSMCs) are the predominant cell type in the medial layer of the aorta, which plays a critical role in the maintenance of aortic wall integrity. VSMCs have been suggested to have contractile and synthetic phenotypes and undergo phenotypic switching to contribute to the deteriorating aortic wall structure. Recently, the unprecedented heterogeneity and diversity of VSMCs and their complex relationship to aortic aneurysms (AAs) have been revealed by high-resolution research methods, such as lineage tracing and single-cell RNA sequencing. The aortic wall consists of VSMCs from different embryonic origins that respond unevenly to genetic defects that directly or indirectly regulate VSMC contractile phenotype. This difference predisposes to hereditary AAs in the aortic root and ascending aorta. Several VSMC phenotypes with different functions, for example, secreting VSMCs, proliferative VSMCs, mesenchymal stem cell-like VSMCs, immune-related VSMCs, proinflammatory VSMCs, senescent VSMCs, and stressed VSMCs are identified in non-hereditary AAs. The transformation of VSMCs into different phenotypes is an adaptive response to deleterious stimuli but can also trigger pathological remodeling that exacerbates the pathogenesis and development of AAs. This review is intended to contribute to the understanding of VSMC diversity in health and aneurysmal diseases. Papers that give an update on VSMC phenotype diversity in health and aneurysmal disease are summarized and recent insights on the role of VSMCs in AAs are discussed.

The life and times of cellular senescence in skeletal muscle: friend or foe for homeostasis and adaptation?

A gradual decline in skeletal muscle mass and function is closely tied to increased mortality and disease risk during organismal aging. Exercise training is the most effective way to enhance muscle health, but the adaptive response to exercise as well as muscle repair potential is blunted in older individuals. Numerous mechanisms contribute to the loss of muscle mass and plasticity as aging progresses. An emerging body of recent evidence implicates an accumulation of senescent ("zombie") cells in muscle as a contributing factor to the aging phenotype. Senescent cells cannot divide but can release inflammatory factors and create an unfavorable environment for homeostasis and adaptation. On balance, some evidence indicates that cells with senescent characteristics can be beneficial for the muscle adaptive process, specifically at younger ages. Emerging evidence also suggests that multinuclear muscle fibers could become senescent. In this review, we summarize current literature on the prevalence of senescent cells in skeletal muscle and highlight the consequences of senescent cell removal on muscle mass, function, and adaptability. We examine key limitations in the field of senescence specifically in skeletal muscle and identify areas of research that require future investigation.NEW & NOTEWORTHY There is evidence to suggest that senescent "zombie" cells may or may not accrue in aging skeletal muscle. When muscle is perturbed regardless of age, senescent-like cells do appear, and the benefits of removing them could be age-dependent. More work is needed to determine the magnitude of accumulation and source of senescent cells in muscle. Regardless, pharmacological senolytic treatment of aged muscle is beneficial for adaptation.

Genetic deletion of Kvβ2 (AKR6) causes loss of muscle function and increased inflammation in mice.

The voltage-gated potassium channels (Kv) are complex ion channels with distinct roles in neurotransmission, electrical conductivity of the heart, and smooth and striated muscle functions. Previously, we demonstrated that deletion of Kvβ2 in mice results in decreased Pax7 protein levels, hindlimb muscles and body weights, and fiber type switching. In the present study, we tested the hypothesis that Kvβ2 regulates skeletal muscle function in mice. The young and old Kvβ2 knockout (KO) and wildtype (WT) mice were utilized to test the aging phenotype and skeletal muscle function. Consistent with our previous finding, we found a significant reduction in hindlimb skeletal muscles mass and body weight in young Kvβ2 KO mice, which was also significantly reduced in old Kvβ2 KO mice compared with age-matched WT mice. Forelimb grip strength, and the hindleg extensor digitorum longus (EDL) muscles force-frequency relations were significantly decreased in young and old Kvβ2 KO mice compared to age-matched WT mice. Analysis of transmission electron microscopy images of EDL muscles in young mice revealed a significant reduction in the sarcomere length for Kvβ2 KO vs. WT. Hematoxylin and eosin-stained tibialis anterior muscles cryosections displayed a significant decrease in the number of medium (2,000-4,000µm2) and largest (>4,000µm2) myofibers area in young Kvβ2 KO vs. WT mice. We also found a significant increase in fibrotic tissue area in young Kvβ2 KO mice compared with age-matched WT mice. Analysis of RNA Seq data of the gastrocnemius muscles (GAS) identified significant increase in genes involved in skeletal muscle development, proliferation and cell fate determination, atrophy, energy metabolism, muscle plasticity, inflammation, and a decrease in circadian core clock genes in young Kvβ2 KO vs. WT mice. Several genes were significantly upregulated (384 genes) and downregulated (40 genes) in young Kvβ2 KO mice compared to age-matched WT mice. Further, RT-qPCR analysis of the GAS muscles displayed a significant increase in pro-inflammatory marker Il6 expression in young Kvβ2 KO mice compared to age-matched WT mice. Overall, the present study shows that deletion of Kvβ2 leads to decreased muscles strength and increased inflammation.

Exercise metabolism and adaptation in skeletal muscle.

Viewing metabolism through the lens of exercise biology has proven an accessible and practical strategy to gain new insights into local and systemic metabolic regulation. Recent methodological developments have advanced understanding of the central role of skeletal muscle in many exercise-associated health benefits and have uncovered the molecular underpinnings driving adaptive responses to training regimens. In this Review, we provide a contemporary view of the metabolic flexibility and functional plasticity of skeletal muscle in response to exercise. First, we provide background on the macrostructure and ultrastructure of skeletal muscle fibres, highlighting the current understanding of sarcomeric networks and mitochondrial subpopulations. Next, we discuss acute exercise skeletal muscle metabolism and the signalling, transcriptional and epigenetic regulation of adaptations to exercise training. We address knowledge gaps throughout and propose future directions for the field. This Review contextualizes recent research of skeletal muscle exercise metabolism, framing further advances and translation into practice.

Estrogen-related Receptor Signaling in Skeletal Muscle Fitness.

Skeletal muscle is a highly plastic tissue that can alter its metabolic and contractile features, as well as regenerative potential in response to exercise and other conditions. Multiple signaling factors including metabolites, kinases, receptors, and transcriptional factors have been studied in the regulation of skeletal muscle plasticity. Recently, estrogen-related receptors (ERRs) have emerged as a critical transcriptional hub in control of skeletal muscle homeostasis. ERRα and ERRγ - the two highly expressed ERR sub-types in the muscle respond to various extracellular cues such as exercise, hypoxia, fasting and dietary factors, in turn regulating gene expression in the skeletal muscle. On the other hand, conditions such as diabetes and muscular dystrophy suppress expression of ERRs in the skeletal muscle, likely contributing to disease progression. We highlight key functions of ERRs in the skeletal muscle including the regulation of fiber type, mitochondrial metabolism, vascularization, and regeneration. We also describe how ERRs are regulated in the skeletal muscle, and their interaction with important muscle regulators (e. g. AMPK and PGCs). Finally, we identify critical gaps in our understanding of ERR signaling in the skeletal muscle, and suggest future areas of investigation to advance ERRs as potential targets for function promoting therapeutics in muscle diseases.

Voluntary wheel running and lithium supplementation improves muscle force production without altering SERCA function in the D2 mdx mouse

Background: Duchenne muscular dystrophy (DMD) is an X-linked recessive muscle wasting disease that, with no cure, leads to early mortality (30-40 years of age). Previous studies have shown that voluntary wheel running can mitigate disease pathology and improve muscle contractility in the preclinical mdx mouse model. We have shown that treating wild-type (WT) mice with a low dose of lithium, a natural inhibitor of glycogen synthase kinase 3, enhanced soleus (SOL) and extensor digitorum longus (EDL) muscle contractility. Our objectives were to test our hypothesis of whether combining VWR with low dose lithium supplementation could provide further benefits to muscle contractility in DBA/2J mdx mice – a model that displays far worse disease severity compared with the traditional C57BL/10 mdx mouse. We also examined if this combined intervention could improve muscle calcium regulation in muscle by assessing sarco(endo)plasmic reticulum Ca 2+ -ATPase (SERCA) function as we have recently shown that SERCA function is drastically impaired in D2 mdx mice, which could also contribute to deficits in muscle force production. Methods: Young (5-6 week old) male D2 WT and mdx mice were ordered from Jackson Laboratory. D2 mdx mice were assigned into each of the following conditions: sedentary ( mdxSED), voluntary wheel running ( mdxVWR), or VWR+lithium chloride ( mdxVWR+Li). The VWR groups were given access to a cagewheel for a total of 6 weeks, and the mdxVWR+Li group were provided a low dose of LiCl (50 mg/kg/day) via drinking water for the entire duration of the study. After 6 weeks, all mice were euthanized and the SOL and EDL muscles were subjected to force-frequency curve analysis (1-160 Hz). SERCA function was assessed by performing SERCA activity assays and a Ca 2+ uptake assay. Results: In the SOL, the combined effect of lithium and VWR improved specific force production to near WT levels across submaximal and maximal frequencies. Specific force production in the mdxVWR+Li group was significantly greater compared to the mdxSED group at all stimulation frequencies. Rate of SOL force development was significantly lower in all mdx groups compared to WT. However, rate of relaxation was only significantly reduced (vs. WT) within the mdxSED group, suggesting that VWR and VWR+Li improved relaxation. This could not be explained by any changes in SERCA function. In the EDL, specific force was significantly (p<0.001) reduced across mdx groups compared to WT; however, of all mdx groups, the mdxVWR+Li produced the most force and was significantly different compared to mdxVWR at 80 and 160 Hz. Rates of force development and relaxation were all slower in all mdx groups compared to WT, and there were no differences in SERCA activity. Conclusions: Combining lithium supplementation with VWR improved SOL and EDL force production in the D2 mdx mouse without any changes to SERCA function. V.A.F is a Tier 2 Canada Research Chair in Muscle Plasticity and Tissue-Remodelling. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Investigating the metabolic changes that accompany skeletal muscle maturation

Skeletal muscle plasticity is imperative for our overall health but diminishes with inactivity and age. As we reach maturity, a shift in nutrient allocation from supporting skeletal muscle hypertrophy to adipogenesis occurs. This pivotal intersection in tissue growth marks the start of a metabolic decline in skeletal muscle and an accumulation of adipose tissue in inactive individuals. If left uncorrected, a loss of skeletal muscle metabolic flexibility can lead to a myriad of metabolic diseases. To define the metabolic changes in skeletal muscle that accompany maturation, samples were collected from the longissimus dorsi (LD, glycolytic muscle), latissimus dorsi (LAT, mixed muscle), and masseter (MS, oxidative muscle) at 20, 53, 87, 120, and 180 days of age from DNA 600 x 241 (DNA Genetics) castrated male pigs that weighed an average of 5.7, 20.8, 42.2, 83.4, and 130.5 kg, respectively. These ages were selected to correspond to tissue growth phases characterized by vital organ growth, intensive muscle hypertrophy, cessation of muscle hypertrophy, and the beginning of unrestricted adipose deposition. Samples were analyzed to determine the abundance of key metabolic enzymes through Western blotting and assess mitochondrial content through real-time PCR. Glucose-6-phosphate dehydrogenase decreased at 87, 120, and 180 d in MS compared to LAT and LD ( P < 0.01), which suggested glycolytic muscles increased nutrient allocation to the pentose phosphate pathway at this time whereas oxidative muscles did not. Moreover, pyruvate dehydrogenase ( P < 0.01) and citrate synthase ( P < 0.01) increased at 120 d, which indicated an increase in metabolites entering oxidative pathways. This increase was accompanied by an increase in mitochondrial DNA at 87 and 120 d ( P < 0.01). Further, glutamic-oxaloacetic transaminase 2 increased between 20 d to 120 d ( P < 0.01) indicating amino acid synthesis peaks at 120 d. These findings have established a metabolic fingerprint associated with the termination of muscle growth and the beginning of adipose tissue growth, which provides the framework for uncovering the regulatory mechanism that modulates nutrient allocation between muscle and fat. Elucidating this mechanism will aid in the discovery of metabolic interventions to combat metabolic diseases. Kansas State University Global Food Systems Seed Grant Program This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Heat Shock Proteins: Important Helpers for the Development, Maintenance and Regeneration of Skeletal Muscles

The skeletal muscle is a highly plastic tissue that shows a remarkable adaptive capacity in response to acute and resistance exercise, and modifies its composition to adapt to use and disuse, a process referred to as muscle plasticity. Heat shock proteins (HSPs), a class of evolutionarily conserved molecular chaperones, have been implicated in the regulation of skeletal muscle plasticity. Here, we summarize key findings supporting the notion that HSPs are important components required to maintain skeletal muscle integrity and functionality. HSPs participate in the transcriptional program required for myogenesis and are activated following muscle exercise and injury. Their dysfunction, either as a consequence of improper expression or genetic mutations, contributes to muscle atrophy and leads to the development of myopathies and peripheral motor neuropathies. Denervation/reinnervation and repeated rounds of nerve degeneration/regeneration have been observed in motor neuropathies, suggesting that an imbalance in HSP expression and function may impair the repair of the neuromuscular junctions. Boosting HSP activity may help preventing muscle atrophy by promoting muscle differentiation and helping the repair of NMJs. Boosting HSP function may also help to combat the development of rhabdomyosarcoma (RMS), a highly aggressive type of pediatric soft tissue sarcoma whose cells have skeletal muscle features but are unable to fully differentiate into skeletal muscle cells.

Indirect regulation of HIPPO pathway by miRNA mediates high-intensity intermittent exercise to ameliorate aging skeletal muscle function.

Exercise-induced microRNA (miRNA) and HIPPO pathways participate in the regulation of skeletal muscle plasticity but their underlying mechanisms remain unclear. We aimed to investigate the effect of high-intensity interval training (HIIT) on miRNA expression and the HIPPO pathway in the skeletal muscle of aging rats to determine its role in the amelioration of muscle aging. Thirty-six 18-month-old female rats were randomly divided into sedentary control (SED, n=12), moderate-intensity continuous training (MICT, n=12), and HIIT (n=12) groups, with continuous exercise for 8 months. Quantitative reverse transcription-polymerase chain reaction, immunoblotting, KEGG enrichment, and dual-luciferase assays were performed on the target skeletal muscle. Compared with the SED group, the MICT and HIIT groups showed a significant trend of improvement in Lee's index and grip strength and a marked increase in skeletal muscle mitochondrial function, apoptosis, antioxidant, and lipolysis-related protein expression. They also exhibited PI3K/AKT pathway activation and a decrease in expression of HIPPO pathway-related proteins; 20 miRNAs were differentially expressed and enriched in the exercise group compared with the SED group, including the HIPPO pathway and metabolic pathways. Further analysis of L6 cells confirmed that miR-182 may target PTEN, which indirectly regulates HIPPO signaling, but not Mob1. the combined application of HIIT and MICT increased the antioxidant and lipolytic capacities of skeletal muscle and improved atrophy of aging skeletal muscle; HIIT was more effective than MICT. This may be related to HIIT-mediated AKT pathway activation and HIPPO pathway inhibition by miRNAs (miR-486 and miR-182).

The role of the mechanistic target of rapamycin complex 1 in the regulation of mitochondrial adaptation during skeletal muscle atrophy under denervation or calorie restriction in mice.

Mechanistic target of rapamycin complex 1 (mTORC1) is a protein complex that regulates skeletal muscle protein synthesis and hypertrophy. mTORC1-mediated signaling activities are activated during denervation-induced skeletal muscle atrophy and suppressed during calorie restriction-induced atrophy. Mitochondria control the qualitative plasticity of skeletal muscles primarily through biogenesis, fusion, and fission. We recently showed that mTORC1 activation contributes toward mitochondrial homeostasis. In this study, we examined the role of mTORC1 in mitochondrial adaptation during denervation- or calorie restriction-induced skeletal muscle atrophy. Seven-week-old Institute of Cancer Research mice were subjected to 14 days of denervation or calorie restriction combined with the administration of the mTORC1 inhibitor-"rapamycin". Our results showed that although mTORC1 inhibition did not alter mitochondrial biogenesis, content and enzyme activity, it suppressed the activation of dynamin-related protein 1 (DRP1), a mitochondrial fission-related protein in denervated muscle, and reduced DRP1 expression in calorie-restricted muscle. Furthermore, calorie restriction-induced mitochondrial fragmentation was partially suppressed by mTORC1 inhibition. Taken together, our results indicate that mTORC1 activation upon denervation and inhibition upon calorie restriction contributes to qualitative changes in muscle plasticity by at least partially regulating the mitochondrial fission response.

Controlling Inflammation Improves Aging Skeletal Muscle Health.

Chronic inflammation is associated with a decline in aging skeletal muscle health. Inflammation also seems to interfere with the beneficial skeletal muscle adaptations conferred by exercise training in older individuals. We hypothesize that the cyclooxygenase pathway is partially responsible for this negative inflammatory influence on aging skeletal muscle health and plasticity.

The molecular athlete: exercise physiology from mechanisms to medals.

Human skeletal muscle demonstrates remarkable plasticity, adapting to numerous external stimuli including the habitual level of contractile loading. Accordingly, muscle function and exercise capacity encompass a broad spectrum, from inactive individuals with low levels of endurance and strength to elite athletes who produce prodigious performances underpinned by pleiotropic training-induced muscular adaptations. Our current understanding of the signal integration, interpretation, and output coordination of the cellular and molecular mechanisms that govern muscle plasticity across this continuum is incomplete. As such, training methods and their application to elite athletes largely rely on a "trial-and-error" approach, with the experience and practices of successful coaches and athletes often providing the bases for "post hoc" scientific enquiry and research. This review provides a synopsis of the morphological and functional changes along with the molecular mechanisms underlying exercise adaptation to endurance- and resistance-based training. These traits are placed in the context of innate genetic and interindividual differences in exercise capacity and performance, with special consideration given to aging athletes. Collectively, we provide a comprehensive overview of skeletal muscle plasticity in response to different modes of exercise and how such adaptations translate from "molecules to medals."

Multimodal high-resolution nano-DESI MSI and immunofluorescence imaging reveal molecular signatures of skeletal muscle fiber types.

The skeletal muscle is a highly heterogeneous tissue comprised of different fiber types with varying contractile and metabolic properties. The complexity in the analysis of skeletal muscle fibers associated with their small size (30-50 μm) and mosaic-like distribution across the tissue tnecessitates the use of high-resolution imaging to differentiate between fiber types. Herein, we use a multimodal approach to characterize the chemical composition of skeletal fibers in a limb muscle, the gastrocnemius. Specifically, we combine high-resolution nanospray desorption electrospray ionization (nano-DESI) mass spectrometry imaging (MSI) with immunofluorescence (IF)-based fiber type identification. Computational image registration and segmentation approaches are used to integrate the information obtained with both techniques. Our results indicate that the transition between oxidative and glycolytic fibers is associated with shallow chemical gradients (<2.5 fold change in signals). Interestingly, we did not find any fiber type-specific molecule. We hypothesize that these findings might be linked to muscle plasticity thereby facilitating a switch in the metabolic properties of fibers in response to different conditions such as exercise and diet, among others. Despite the shallow chemical gradients, cardiolipins (CLs), acylcarnitines (CAR), monoglycerides (MGs), fatty acids, highly polyunsaturated phospholipids, and oxidized phospholipids, were identified as molecular signatures of oxidative metabolism. In contrast, histidine-related compounds were found as molecular signatures of glycolytic fibers. Additionally, the presence of highly polyunsaturated acyl chains in phospholipids was found in oxidative fibers whereas more saturated acyl chains in phospholipids were found in glycolytic fibers which suggests an effect of the membrane fluidity on the metabolic properties of skeletal myofibers.

Murine Models of Tenotomy-Induced Mechanical Overloading and Tail-Suspension-Induced Mechanical Unloading.

Skeletal muscle is a highly plastic tissue that can alter its mass and strength in response to mechanical stimulation, such as overloading and unloading, which lead to muscle hypertrophy and atrophy, respectively. Mechanical loading in the muscle influences muscle stem cell dynamics, including activation, proliferation, and differentiation. Although experimental models of mechanical overloading and unloading have been widely used for the investigation of the molecular mechanisms regulating muscle plasticity and stem cell function, few studies have described the methods in detail. Here, we describe the appropriate procedures for tenotomy-induced mechanical overloading and tail-suspension-induced mechanical unloading, which are the most common and simple methods to induce muscle hypertrophy and atrophy in mouse models.

RNA-Sequencing Muscle Plasticity to Resistance Exercise Training and Disuse in Youth and Older Age

Maintenance of skeletal muscle mass and function is critical to health and wellbeing throughout the lifespan. However, disuse through reduced physical activity (e.g., sedentarism), immobilisation, bed rest or microgravity has significant adverse effects on skeletal muscle health. Conversely, resistance exercise training (RET) induces positive muscle mass and strength adaptations. Several studies have employed microarray technology to understand the transcriptional basis of muscle atrophy and hypertrophy after disuse and RET, respectively, to devise fully effective therapeutic interventions. More recently, rapidly falling costs have seen RNA-sequencing (RNA-seq) increasingly applied in exploring muscle adaptations to RET and disuse. The aim of this review is to summarise the transcriptional responses to RET or disuse measured via RNA-seq in young and older adults. We also highlight analytical considerations to maximise the utility of RNA-seq in the context of skeletal muscle research. The limited number of muscle transcriptional signatures obtained thus far with RNA-seq are generally consistent with those obtained with microarrays. However, RNA-seq may provide additional molecular insight, particularly when combined with data-driven approaches such as correlation network analyses. In this context, it is essential to consider the most appropriate study design parameters as well as bioinformatic and statistical approaches. This will facilitate the use of RNA-seq to better understand the transcriptional regulators of skeletal muscle plasticity in response to increased or decreased use.

The inflammatory response, a mixed blessing for muscle homeostasis and plasticity.

Skeletal muscle makes up almost half the body weight of heathy individuals and is involved in several vital functions, including breathing, thermogenesis, metabolism, and locomotion. Skeletal muscle exhibits enormous plasticity with its capacity to adapt to stimuli such as changes in mechanical loading, nutritional interventions, or environmental factors (oxidative stress, inflammation, and endocrine changes). Satellite cells and timely recruited inflammatory cells are key actors in muscle homeostasis, injury, and repair processes. Conversely, uncontrolled recruitment of inflammatory cells or chronic inflammatory processes leads to muscle atrophy, fibrosis and, ultimately, impairment of muscle function. Muscle atrophy and loss of function are reported to occur either in physiological situations such as aging, cast immobilization, and prolonged bed rest, as well as in many pathological situations, including cancers, muscular dystrophies, and several other chronic illnesses. In this review, we highlight recent discoveries with respect to the molecular mechanisms leading to muscle atrophy caused by modified mechanical loading, aging, and diseases. We also summarize current perspectives suggesting that the inflammatory process in muscle homeostasis and repair is a double-edged sword. Lastly, we review recent therapeutic approaches for treating muscle wasting disorders, with a focus on the RANK/RANKL/OPG pathway and its involvement in muscle inflammation, protection and regeneration processes.