do myokines promote muscle degeneration

One of the best-known processes associated with autocrine/paracrine secretory activity concerns the mechanisms involved in controlling and restoring muscle mass in different conditions, both physiological, such as aging or microgravity, and pathological, such as diabetes, heart failure or cancer. Park H.-S., Kim H.C., Zhang D., Yeom H., Lim S.-K. In humans, myokines released as a consequence of muscular contraction (and therefore, during physical activity) constitute a particular class known as Exerkines, which, by paracrine/endocrine means, are able to mediate beneficial effects throughout the body [1]. increased visceral adiposity and muscle atrophy. The myogenic satellite cell has an anatomically defined specialized niche that ultimately governs the state of this cell population (quiescence, activation, proliferation, etc.). Released cytokines, neurotrophic factors, growth factors and oxygen tension, such as Hif1, Hif2, NO and Vegf, collectively orchestrate and modulate the status of the satellite cell pool. In a mouse model of hindlimb ischemia, NGF gene transfection could enhance the expression of its protein, and this induced an increase in the presence of type I muscle fibers. Myokines, Adipokines, Cytokines in Muscle Pathophysiology. One of the most interesting scenarios to test this hypothesis is muscle ageing known as sarcopenia. In humans, regenerating muscle fibers from patients affected by Duchenne and Becker muscular dystrophies consistently express NGF, as do myofibroblasts and mast cells. GDF11 was initially thought to mimic the action of myostatin. As abnormal glucose and lipid metabolism, diabetes and obesity are risk factors for cardiovascular disease, irisin, which is an important regulator of energy metabolism, could play a key role in maintaining a healthy cardiovascular system [140]. Gomes M.J., Martinez P.F., Pagan L.U., Damatto R.L., Mariano Cezar M.D., Ruiz Lima A.R., Okoshi K., Okoshi M.P. An Overview About the Biology of Skeletal Muscle Satellite Cells. However, NGF stimulation significantly enhanced the engraftment efficiency of adult staminal cells transplanted in the dystrophic muscle of mdx mice, resulting in the regeneration of numerous dystrophin-positive muscle fibers [52]. Kim H., Wrann C.D., Jedrychowski M., Vidoni S., Kitase Y., Nagano K., Zhou C., Chou J., Parkman V.-J.A., Novick S.J., et al. The second situation arises when the activities of the IGF and insulin chain are dysregulated in the so-called insulin/IGF resistance state. At least one of the intracellular mechanisms by which irisin acts in the target cell is linked to the active regulation of cellular autophagy processes. Physical exercise induces a network of alterations in the transcriptome and proteome of the skeletal muscle, resulting in modifications of the muscle physiology. However, irisin also appears to have a positive effect on cognitive function and to play a role in bone metabolism regulation [2,123]. Interaction of CREB and PGC-1 Induces Fibronectin Type III Domain-Containing Protein 5 Expression in C2C12 Myotubes. These muscle-secreted factors exert biological functions in muscle itself (autocrine effect) or on short- or long-distant organs (paracrine/endocrine effects) and control processes such as metabolism, angiogenesis, or inflammation. Multifactorial Mechanism of Sarcopenia and Sarcopenic Obesity. Role of Myostatin, IGF-1, NGF, S100 and irisin are examples of specific myokines that have peculiar features in their mechanisms of action. They were recently shown to have different types of myogenic cells, all of which have exceptional regenerative potential. Skeletal muscle wasting and renewal: a pivotal role of myokine IL-6 The Potential of Endurance Exercise-Derived Exosomes to Treat Metabolic Diseases. Physical activity improves the prognosis of cancer patients, partly by contrasting the associated muscle wasting (cachexia), through still unknown mechanisms. Many growth factors, cytokines and myokines produced by skeletal muscle cells play critical roles in local regulation of the inflammatory process and skeletal muscle regeneration . For example, some studies that used chronic-exercise protocols were unable to detect changes in circulating levels of irisin, but these findings should not be interpreted as a lack of effect of exercise on irisin secretion. Skeletal muscle (40% of body weight) is the main reservoir of irisin and, therefore, determines its circulating levels. Bowen T.S., Schuler G., Adams V. Skeletal Muscle Wasting in Cachexia and Sarcopenia: Molecular Pathophysiology and Impact of Exercise Training. The causes of sarcopenia are generally attributable to natural aging processes, which are neither identified with sufficient certainty nor tested with adequate clarity. muscle is an endocrine organ that produces and releases cytokines, termed 'myokines' [12-15] (Box 1). Relationship of Serum Irisin Levels to Prevalence and Progression of Coronary Artery Calcification: A Prospective, Population-Based Study. Chem. In effect, despite the efforts of various researchers, whether irisin protects the heart against myocardial ischemia and reperfusion injury (I/R) is still unknown. However, although our understanding of molecular mechanisms regulating muscle atrophy/muscle weakness has substantially progressed, there is no specific treatment for muscle atrophy. Shimba Y., Togawa H., Senoo N., Ikeda M., Miyoshi N., Morita A., Miura S. Skeletal Muscle-Specific PGC-1 Overexpression Suppresses Atherosclerosis in Apolipoprotein E-Knockout Mice. In particular, IGF-1 stimulates protein synthesis in skeletal muscle via the PI3K/Akt/mTOR and PI3K/Akt/GSK3 pathways. Similarly, in vitro contraction of human skeletal muscle cells by electrical pulse stimulation increased PPARGC1A mRNA levels but had no effect on FNDC5 mRNA levels [149]. Nevertheless, its biology is not as simple as it may appear. Clin. The adjacent differentiated myofiber, innervating motor neurons, infiltrating inflammatory cells and vascularization collectively establish the niche in which the satellite cell resides [56]. Forcina L., Miano C., Scicchitano B., Musar A. These factors bind to activin type IIA and IIB receptors (ActRIIA/B) and TGF receptors (TGFRII) in the plasma membrane. Zhang D., Tan X., Tang N., Huang F., Chen Z., Shi G. Review of Research on the Role of Irisin in Tumors. In: Xiao J., editor. In the last decade, clear evidence has emerged that the cellular components of skeletal muscle are important sites for the release of proteins and peptides called myokines, suggesting that skeletal muscle plays the role of a secretory organ. Biochem. (PDF) Mitochondria Homeostasis and Oxidant/Antioxidant - ResearchGate Cell. Morozzi G., Beccafico S., Bianchi R., Riuzzi F., Bellezza I., Giambanco I., Arcuri C., Minelli A., Donato R. Oxidative Stress-Induced S100B Accumulation Converts Myoblasts into Brown Adipocytes via an NF-B/YY1/miR-133 Axis and NF-B/YY1/BMP-7 Axis. At the same time, reduced Akt activity causes the release of FoxO from segregation sites in the cytoplasm, and this triggers an atrophic cascade linked to the expression of atrogenes belonging to the proteolytic pathways of lysosomal autophagy and the ubiquitin cycle in the proteasome [37]. Myostatin is abundant in skeletal muscle, but it is also expressed in adipose tissue and heart muscle; it is widely conserved on the evolutionary scale, and the effect observed in mice is also found in dogs, sheep, cattle and humans [33]. Inclusion in an NLM database does not imply endorsement of, or agreement with, Hsu K., Champaiboon C., Guenther B.D., Sorenson B.S., Khammanivong A., Ross K.F., Geczy C.L., Herzberg M.C. Off. A moderate level of oxidative stress, as occurs in non-exhaustive exercise, up-regulates PGC1 by promoting oxidative fiber formation at the expense of glycolytic fiber formation, increasing muscle mass and strength and resistance to muscle wasting, together with enhancing the early stages of adult muscle stem cell activation and proliferation [154]. Forced Exercise Increases Muscle Mass in EAE Despite Early Onset of Disability. The Age-Related Loss of Skeletal Muscle Mass and Function: Measurement and Physiology of Muscle Fibre Atrophy and Muscle Fibre Loss in Humans. Conversely, the expression of genes that are involved in glycogenolysis (PYGM) or gluconeogenesis (PCK1) is drastically inhibited [145]. Detection and Quantitation of Circulating Human Irisin by Tandem Mass Spectrometry. The Ever-Expanding Myokinome: Discovery Challenges and Therapeutic Implications. In mammalian skeletal muscle, contraction occurs because the intracellular Ca2+ concentration increases by about 100 times compared to that at rest. Mai S., Grugni G., Mele C., Vietti R., Vigna L., Sartorio A., Aimaretti G., Scacchi M., Marzullo P. Irisin Levels in Genetic and Essential Obesity: Clues for a Potential Dual Role. Soc. This hypothesis is supported by both in vivo and in vitro experiments that showed that GTPase OPA1, which is responsible for the regulation of mitochondrial dynamics and is crucial for adapting mitochondrial function and preserving cellular health, is downregulated in the infarcted heart, whereas irisin treatment upregulated its expression and protected cardiomyocytes from further damage after myocardial infarction [135]. The reduction in muscle size is known as hypotrophy and can result from a decrease in cell size due to either the loss of cellular content or an alteration in protein synthesis. A myokine is one of several hundred cytokines or other small proteins (~5-20 kDa) and proteoglycan peptides that are produced and released by skeletal muscle cells (muscle fibers) in response to muscular contractions. demonstrated that C2C12 myoblasts, a mouse skeletal muscle myoblast cellular model, secreted NGF to the media by playing an autocrine proliferative role, whereas it was not secreted by C2C12 myotubes [55]. Before Recent studies have suggested that NGF stimulates myoblast differentiation and collagen synthesis, but the regulatory mechanism remains poorly defined [58]. However, no data have been published on this issue, and the statement is, therefore, only a working hypothesis. Role of Myokines in Regulating Skeletal Muscle Mass and Function Notably, PGC1 transcription is controlled by cAMP via the CREB protein. Indeed, irisin has been shown to bind to proteins of the V class of integrins, and biophysical studies have identified interaction surfaces between irisin and V/5 integrins. Raffaello A., Milan G., Masiero E., Carnio S., Lee D., Lanfranchi G., Goldberg A.L., Sandri M. JunB Transcription Factor Maintains Skeletal Muscle Mass and Promotes Hypertrophy. When we try to interpret these apparently contradictory data, we need to reflect on what Nikolaos Perakakis and his collaborators wrote When interpreting the results of these exercise-based studies, one must remember that a high degree of heterogeneity exists between study designs, which makes reliable and generalizable conclusions difficult. Camerino C., Conte E., Carrat M.R., Fonzino A., Lograno M.D., Tricarico D. Oxytocin/Osteocalcin/IL-6 and NGF/BDNF mRNA Levels in Response to Cold Stress Challenge in Mice: Possible Oxytonic Brain-Bone-Muscle-Interaction. Mapping mammalian biochemistry is a sizable task, and much of that biochemistry remains poorly understood and categorized. J. Physiol. Sartori R., Schirwis E., Blaauw B., Bortolanza S., Zhao J., Enzo E., Stantzou A., Mouisel E., Toniolo L., Ferry A., et al. Autophagy is a crucial step in the homeostasis of nutrients and energy in the cell and largely acts on cellular catabolism by facilitating lysosomal degradation and promoting the recovery and reuse of damaged proteins and organelles. Autophagy Maintains Stemness by Preventing Senescence. Muscle injury with exercise releases fibroblast growth factor 2 (FGF-2) from wounded myocytes into the circulation, and skeletal myocytes also secrete insulin-like growth factor 1 (IGF-1) into the bloodstream in addition to liver-derived IGF-1.Myofiber hypertrophy is thought to increase IGF-1 expression and . A few years later, this factor was better defined, and it was found to be identifiable as NGF, normally produced and secreted by the nervous system [50]. Aged Mstn-null (Mstn/) muscles, which have reduced sarcopenia, also contain increased basal antioxidant enzyme levels and lower NF-B levels, indicating efficient scavenging of excess ROS. Das D.K., Graham Z.A., Cardozo C.P. Brenmoehl J., Albrecht E., Komolka K., Schering L., Langhammer M., Hoeflich A., Maak S. Irisin Is Elevated in Skeletal Muscle and Serum of Mice Immediately after Acute Exercise. Information on the molecular mechanisms and structural changes that occur in this tissue with age originates from studies on muscle biopsies, including from humans. Microarray analysis performed on human muscle biopsies obtained up to six hours after IL-6 infusion identified the dysregulation of a small set of genes. The site is secure. Muscle Stem Cells in Development, Regeneration, and Disease. wrote the manuscript. FNDC5 and Irisin in Humans: I. Predictors of Circulating Concentrations in Serum and Plasma and II. When Myostatin acts on the whole cellular apparatus of the muscle through the receptor ActRII/B, the intracellular domain of the ligandreceptor complex forms a serine/threonine kinase-based complex that is transferred to the nucleus to regulate the transcription of genes involved in the proliferation and differentiation of skeletal muscle stem cells. Irisin Counteracts High Glucose and Fatty Acid-Induced Cytotoxicity by Preserving the AMPK-Insulin Receptor Signaling Axis in C2C12 Myoblasts. Importantly, IGF-1 levels and downstream IGF-1R signaling are suppressed in many chronic disease conditions, such as cachexia and fibrosis [77]. La Rovere R.M.L., Quattrocelli M., Pietrangelo T., Di Filippo E.S., Maccatrozzo L., Cassano M., Mascarello F., Barthlmy I., Blot S., Sampaolesi M., et al. Although there is much overlap between the two proteins in terms of both amino acid sequence and receptor and signaling pathways, accumulating evidence suggests that these two ligands have distinct functions [43]. Antimyostatin Treatment in Health and Disease: The Story of Great Expectations and Limited Success. Adult skeletal tissue is composed of heterogeneous population of cells that constantly self-renew by means of a controlled process of activation and proliferation of tissue-resident stem cells named satellite cells. Consequently, multiple TGF- family ligands can cooperate with, or counteract, myostatin activity, competing for the same receptor complexes and Smad-signaling proteins [39]. Fan G., Biocca S., Fulle S., Mariggi M.A., Belia S., Calissano P. The S-100: A Protein Family in Search of a Function. Specifically, activation of mTOR is a consequence of the role that insulin and IGF-1 play synergistically in controlling muscle mass. Moreno M., Moreno-Navarrete J.M., Serrano M., Ortega F., Delgado E., Sanchez-Ragnarsson C., Valds S., Botas P., Ricart W., Fernndez-Real J.M. In addition, S100A9 has also been shown to promote cellular senescence of bone marrow stromal cells via the TLR4/NLRP3 pathway and IL-1 secretion [114]. government site. Wilkinson D.J., Piasecki M., Atherton P.J. Available data indicate that cell death promoted by S100A8/A9 occurs through cross-talk of mitochondria and lysosomes via ROS and BNIP3 [113]. Pharmacol. Donato R. RAGE: A Single Receptor for Several Ligands and Different Cellular Responses: The Case of Certain S100 Proteins. Suh J., Lee Y.-S. Sartori R., Milan G., Patron M., Mammucari C., Blaauw B., Abraham R., Sandri M. Smad2 and 3 Transcription Factors Control Muscle Mass in Adulthood. Costamagna D., Berardi E., Ceccarelli G., Sampaolesi M. Adult Stem Cells and Skeletal Muscle Regeneration. Chang J.S., Kim T.H., Nguyen T.T., Park K.-S., Kim N., Kong I.D. A Role for Myokines in Muscle-Bone Interactions - LWW Udeh R., Advani S., de Guadiana Romualdo L.G., Dolja-Gore X. Calprotectin, an Emerging Biomarker of Interest in COVID-19: A Systematic Review and Meta-Analysis. The daily difference between MPS and MPB defines the net protein balance (NPB), which is a key regulator of overall skeletal muscle mass. However, it remains to be established: (1) whether there is a direct interaction between myokines and antioxidant action and the identity of their intracellular target, (2) whether physical activity has the same effect in young and old subjects and the related intracellular pathways activated and (3) whether pharmacological and/or physical induction of muscle myokines is effective in reversing the oxidative stress process present in sarcopenic muscle. As a consequence of this, ROS overproduction in myoblasts causes S100B accumulation and stimulates NF-B activity, which causes S100B up-regulation. Pignataro P., Dicarlo M., Zerlotin R., Zecca C., DellAbate M.T., Buccoliero C., Logroscino G., Colucci S., Grano M. FNDC5/Irisin System in Neuroinflammation and Neurodegenerative Diseases: Update and Novel Perspective. In contrast, no increased secretory activity was recorded after just IL-6 infusion. . In particular, mitochondria play a crucial role during neurogenesis and in post-mitotic neurons, providing the energy required for neuronal activity and synaptic function. Studies in humans and rodents have reported that myokines are important mediators of the physical benefits of exercise and . Anti-Infective Protective Properties of S100 Calgranulins. Both types of delivery vehicles can carry proteins and/or nucleic acids and are involved in a variety of physiological and pathological processes. Decreased mTOR activity also leads to the stimulation of autophagy through ULK1/2 signaling [80]. The skeletal muscle tissue synthesizes and secretes NGF [53], and its expression and its p75NTR receptor in myoblasts are developmentally regulated during myogenesis [54]. What Muscles Do Planks Work? Experts Explain. Nike.com Myokines: A potential key factor in development, treatment, and For these reasons, IGF-1 therapy has been able to exert clear mitochondrial protective effects and antioxidant and neuroprotective effects [86]. S-100, a little-known myokine, is capable of modulating contractile activity and force generation (but also acts on myogenesis), and finally, the extracellular level of irisin, which is not only the most recently discovered but also certainly one of the most interesting of the known myokines, is strongly linked to physical activity and is able to correlate the homeostatic effect on the secreting muscle with that on other systems (skeletal and cardiovascular systems in primis), forming a functional UNICUM of utmost importance for understanding the senescence process. Cachexia affects prognosis and survival in cancer, and it is estimated that it will be the ultimate cause of death for up to 30% of cancer p This occurs because miR-19b irisin-dependent expression can reactivate the AKT/mTOR signaling pathway blocked by H2O2 in H9c2 cells. The term insulin/IGF resistance describes a phenomenon in which the body exhibits blunted activation of the IR and IGF1R signaling cascades. NGF is critical for neuronal differentiation and maintenance through the activation of TrkA and p75 receptors. Although the available data are certainly insufficient to clearly delineate the proteins mechanism of action, they indicate that the availability of irisin (which does not act only in skeletal muscle) is directly proportional to its antioxidant capacity. This work was supported by the University G. Tsoporis J.N., Izhar S., Proteau G., Slaughter G., Parker T.G. Int. Myokine dysfunction can cause and aggravate obesity, sarcopenia, and SO. Riuzzi F., Sorci G., Sagheddu R., Chiappalupi S., Salvadori L., Donato R. RAGE in the Pathophysiology of Skeletal Muscle. Furthermore, when C2C12 cells undergo a reoxygenation insult, they have a more oxidized redox potential following the generation of reactive oxygen species (ROS). Treatment of human myocytes with recombinant irisin significantly increases glucose and free fatty acid uptake, similar to that induced by insulin. The role of oxidative stress in sarcopenia. Anti Allergy Agents Med. Popov D.V., Lysenko E.A., Makhnovskii P.A., Kurochkina N.S., Vinogradova O.L. In this regard, at least two other considerations need to be addressed to better understand the complex interaction linking the biological effects of insulin and IGFs. Insulin-like growth factors are key factors in the regulation of both anabolic and catabolic pathways in skeletal muscle. Flori L., Testai L., Calderone V. The Irisin System: From Biological Roles to Pharmacological and Nutraceutical Perspectives. Exercise-Induced Irisin Secretion Is Independent of Age or Fitness Level and Increased Irisin May Directly Modulate Muscle Metabolism through AMPK Activation. Bethesda, MD 20894, Web Policies Fig. Int. Using myoblasts as a substrate, a relationship has been shown to exist between NGF and the type of muscle fiber formed at the end of the differentiation process. These effects can increase the risk of . The Role of Nuclear Insulin and IGF1 Receptors in Metabolism and Cancer. Reducing the insulin/IGF1 receptor pathway, well known to promote longevity, also improves sarcopenia [22]. Rectus abdominis: When you think of the traditional "six-pack abs," these muscles are at the forefront. ROS and myokines promote muscle adaptation to exercise Furthermore, irisin treatment suppressed mitochondrial swelling and protected mitochondria function [134]. Ettinger et al. Huang-Doran I., Zhang C.-Y., Vidal-Puig A. Extracellular Vesicles: Novel Mediators of Cell Communication in Metabolic Disease. We asked whether aerobic exercise causes secretion by skeletal muscles of proteins (myokines) that may contrast cachexia. Under these experimental conditions, plasma calprotectin increased five-fold. Finally, in the opinion of many, IGF-1, Akt/Protein Kinase B and the target signaling pathway mTOR constitute the key link between muscle contraction and protein synthesis in its fibers. Antioxidant vitamins C or E may help muscle mass and function . Abnormal glucose and lipid metabolism, diabetes and obesity are risk factors for cardiovascular disease, so irisin has a potential role in maintaining cardiovascular homeostasis [131]. Neurotrophins are a family of growth factors that regulate the trophism, differentiation and plasticity of nerve cells. Evidence against a Beneficial Effect of Irisin in Humans. Elevated plasma levels of calprotectin have been reported in a variety of chronic inflammatory conditions, including rheumatoid arthritis, inflammatory bowel disease, cancer and COVID-19 disease [103,104]. Carrero-Rojas G., Bentez-Temio B., Pastor A.M., Davis Lpez de Carrizosa M.A. In addition, studies in C2C12 muscle cells also demonstrated that the cAMP-activated protein kinase pathway is involved in PGC1/irisin expression [7]. A. Media conditioned b Neurotrophins are important modulators of myogenic regeneration and act by promoting the proliferation of myoblasts, improving myogenic fusion rates and protecting myotubes from stress stimuli, including oxidative stress. Vainshtein A., Sandri M. Signaling Pathways That Control Muscle Mass. (2017) considered low serum irisin concentration as a sensitive molecular marker for muscle weakness and wasting and Park et al. The aim of this review was to show the role of some well-known myokines in the maintenance of homeostasis. Intriguingly, exercise also transiently induces the production of both reactive oxygen species (ROS) and some inflammatory cytokines in skeletal muscle. Bak D.-H., Na J., Im S.I., Oh C.T., Kim J.-Y., Park S.-K., Han H.J., Seok J., Choi S.Y., Ko E.J., et al. Bodine S.C., Stitt T.N., Gonzalez M., Kline W.O., Stover G.L., Bauerlein R., Zlotchenko E., Scrimgeour A., Lawrence J.C., Glass D.J., et al. the contents by NLM or the National Institutes of Health. As a result, these muscles are better protected against stress and sarcopenia [64]. Moreover, studies that did not show that PGC1 was upregulated by exercise might have not used the appropriate experimental model to investigate the relationship between irisin and exercise. For example, some investigators observed that irisin levels increased from 3.6 to 4.3 ng/mL in the serum after 12 weeks of high-intensity aerobic training in humans [151]. Vaughan R.A., Gannon N.P., Barberena M.A., Garcia-Smith R., Bisoffi M., Mermier C.M., Conn C.A., Trujillo K.A. Norheim F., Langleite T.M., Hjorth M., Holen T., Kielland A., Stadheim H.K., Gulseth H.L., Birkeland K.I., Jensen J., Drevon C.A. Satellite cells of sarcopenic muscle and proliferating aged myoblasts accumulate ROS due to altered mitochondrial homeostasis and impaired antioxidant systems [107]. In rodents, aged flies and worms, dietary restriction improves muscle performance. In sum, myokines affect complex multi-organ processes, such as skeletal muscle trophism, metabolism, angiogenesis and immunological response to different physiological (physical activity, aging, etc.) Involvement of Heme Oxygenase-1 and Antioxidazing Enzymes Superoxide Dismutase-2 and Glutathione Peroxidase. Pasquale Paolisso. Spratt D.E., Barber K.R., Marlatt N.M., Ngo V., Macklin J.A., Xiao Y., Konermann L., Duennwald M.L., Shaw G.S. Diao Y.-P., Cui F.-K., Yan S., Chen Z.-G., Lian L.-S., Guo L.-L., Li Y.-J. Shabani F., Farasat A., Mahdavi M., Gheibi N. Calprotectin (S100A8/S100A9): A Key Protein between Inflammation and Cancer. In response to energy metabolism, such as that required to initiate and sustain exercise, muscle upregulates the production and release of blood-borne soluble factors, collectively known as. In a study carried out on a mouse myogenic cell line (C2C12), myoblasts in which irisin was overexpressed by transfection were observed to have a significant increase in cell viability and a decrease in apoptosis induced by increased glucose [156]. Nutrition Chapter 10 Flashcards | Quizlet Targeting Age-Dependent Functional and Metabolic Decline of Human Frontiers Media SA, Dec 24, 2020 - Science - 256 pages. The table shows the myokines selected according to the following criteria: (1) the manifest ability of the myokine to act both from the inside of the cell and in an autocrine fashion; (2) the existence of a definite relation between the presence of the myokine with the modulation of the ROS balance of the fibers involved in regulatory processes (metabolic or regenerative) of muscle aging. Physiology and Role of Irisin in Glucose Homeostasis. BMP Signaling Controls Muscle Mass. Chiappalupi S., Sorci G., Vukasinovic A., Salvadori L., Sagheddu R., Coletti D., Renga G., Romani L., Donato R., Riuzzi F. Targeting RAGE Prevents Muscle Wasting and Prolongs Survival in Cancer Cachexia.
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