do myokines promote muscle degenerationdo myokines promote muscle degeneration

cachexia, is associated with different types of cancer such as pancreatic, colorectal, lung, liver, gastric and esophageal. Table 1 summarizes the principal information on the selected myokines. 1Department of Neuroscience Imaging and Clinical Sciences, University G. This process is the result of many cellular changes. Information on the molecular mechanisms and structural changes that occur in this tissue with age originates from studies on muscle biopsies, including from humans. As such, measurement of MPS is the primary goal in human metabolic research [82]. In contrast, a five-fold up-regulation of S100A8 and S100A9 mRNA was recorded after 3 h ergometer exercise in healthy young males. Satellite cell activation, proliferation, differentiation and subsequent fusion generate ex novo other multi-nucleated cells (myotubes) with characteristics similar to the fibers constituting the originating muscle. This is achieved by promoting oxidative phosphorylation, leading to increased ROS generation and the need to increase mitochondrial biogenesis, along with control of mitophagy mechanisms [67]. muscle is an endocrine organ that produces and releases cytokines, termed 'myokines' [12-15] (Box 1). Skeletal Muscle Aging: Influence of Oxidative Stress and Physical Exercise. Fulle S., Mariggi M.A., Belia S., Petrelli C., Ballarini P., Guarnieri S., Fan G. Rapid Desensitization of PC12 Cells Stimulated with High Concentrations of Extracellular S100. PDF ROS and myokines promote muscle adaptation to exercise - Cell Press Specifically, the proNGF/p75NTR pathway facilitates a slow-to-fast fiber type transition by counteracting the expression of slow myosin heavy chain. PGC1 is highly expressed in tissues with high oxidative capacity and acts as a key metabolic regulatory factor in many physiological situations involving muscle, such as endurance programs and the resulting change in the ratio of fast-to-slow fibers that are often associated with changes in insulin sensitivity. Essential Points Myokines are defined as cytokines and other peptides that are produced, expressed and released by muscle fibers and exert either autocrine, paracrine, or endocrine effects Kurdiova T., Balaz M., Mayer A., Maderova D., Belan V., Wolfrum C., Ukropec J., Ukropcova B. Exercise-Mimicking Treatment Fails to Increase Fndc5 mRNA & Irisin Secretion in Primary Human Myotubes. Perakakis N., Triantafyllou G.A., Fernndez-Real J.M., Huh J.Y., Park K.H., Seufert J., Mantzoros C.S. In cardiomyoblasts exposed to hypoxia/reoxygenation, irisin treatment significantly attenuated hypoxia/reoxygenation, as indicated by the reduction in LDH loss and apoptotic cardiomyocytes. IGF-1 also enhances skeletal muscle regeneration through the activation of satellite cells, thus resulting in a stimulus for hyperplasia. de Perini A., Dimauro I., Duranti G., Fantini C., Mercatelli N., Ceci R., Di Luigi L., Sabatini S., Caporossi D. The p75NTR-Mediated Effect of Nerve Growth Factor in L6C5 Myogenic Cells. The Role of the IGF-1 Signaling Cascade in Muscle Protein Synthesis and Anabolic Resistance in Aging Skeletal Muscle. A PGC1--Dependent Myokine That Drives Brown-Fat-like Development of White Fat and Thermogenesis. Shi X., Garry D.J. Currently, therapeutic interventions based on decreasing myostatin levels have not been established to successfully treat muscle wasting. Based on data collected from many laboratories, we infer that, among the myokines discussed here, irisin could be one of those most involved in regulating the oxidative state, mitochondrial genesis and the repair of cellular structures damaged by contractile activity that occurs in the presence of oxidative stress. Insulin-like growth factors are key factors in the regulation of both anabolic and catabolic pathways in skeletal muscle. 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. and R.M. Scicchitano B.M., Pelosi L., Sica G., Musar A. 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]. Forcina L., Miano C., Scicchitano B., Musar A. Kwon J.H., Moon K.M., Min K.-W. Exercise-Induced Myokines Can Explain the Importance of Physical Activity in the Elderly: An Overview. (2017) considered low serum irisin concentration as a sensitive molecular marker for muscle weakness and wasting and Park et al. After adjustment for cardiometabolic risk factors, the inverse association between serum irisin concentration and coronary artery calcification progression persisted [137]. 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. Christian C.J., Benian G.M. mRNA Expression and Circulating Concentrations in Response to Weight Loss and Exercise. Res. 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. 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. More information on the listed myokines is described in specific paragraphs. Myokines are hypothesized as a signal conveying physiological information to skeletal muscle, possibly to "fine-tune" other regulatory pathways. In particular, MGF, IGF-1, S100 and irisin are able to counteract oxidative stress, thus improving mitochondrial function and reducing ROS production; conversely, Myostatin increases oxidative stress that in turn increases the myostatin level. Outside muscle cells, extrinsic factors, including some myokines associated with the niche, and intrinsic cell-autonomous factors contribute to determining and/or counteracting age-related changes in muscle cells. Hoogaars W.M.H., Jaspers R.T. Past, Present, and Future Perspective of Targeting Myostatin and Related Signaling Pathways to Counteract Muscle Atrophy. Skeletal muscle aging is a complex process that is associated with a decrease in mass, strength and velocity of contraction, known as sarcopenia. Clin. Here, too, the increased energy requirements of contractile function lead to an increase in oxidative phosphorylation and ROS generation and the need to act on both mitochondrial biogenesis and mitophagy. Gonzalez-Gil A.M., Elizondo-Montemayor L. The Role of Exercise in the Interplay between Myokines, Hepatokines, Osteokines, Adipokines, and Modulation of Inflammation for Energy Substrate Redistribution and Fat Mass Loss: A Review. Biochem. Neurotrophins and Their Receptors: A Convergence Point for Many Signalling Pathways. On the contrary, no measurements have been made to verify the correlation between the state of oxidative stress that results from ischemic atrophy and myokine transfection [65]. Sartori R., Schirwis E., Blaauw B., Bortolanza S., Zhao J., Enzo E., Stantzou A., Mouisel E., Toniolo L., Ferry A., et al. While myostatin may be the best-known member of the TGF superfamily, this family of growth factors consists of at least thirty elements. Role of Myokines in Regulating Skeletal Muscle Mass and Function . Abdominal Muscles. The https:// ensures that you are connecting to the 0 Reviews. 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]. During muscle development or regeneration, myocytes transiently produce NGF, as well as its tyrosine-kinase and p75 receptors, but when myoblasts were screened for the expression of NGF receptors, only p75NTR was detected, while the high-affinity NGF receptor, TrkA, was not present [57]. Rectus abdominis: When you think of the traditional "six-pack abs," these muscles are at the forefront. 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. Conversely, it has also been shown that circulating irisin levels increase with increasing fat mass, particularly in obesity. 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. Homage to Rita Levi-Montalcini, the Queen of Modern Neuroscience: Homage to Rita Levi-Montalcini. In summary, increased expression of irisin in the heart and/or irisin treatment in cardiomyocytes increased ROS production, resulting in caspase-9-dependent apoptotic processes [132]. Black arrows represent direct correlations with sarcopenia, while blue arrows represent indirect ones. In addition, it has been reported that the p75NTR receptor could represent a key regulator of the NGF-mediated myoprotective effect on satellite cells, but the precise function of the NGF/p75 signaling pathway in myogenic cell proliferation, survival and differentiation remains fragmented and controversial [59]. Donato R. S100: A Multigenic Family of Calcium-Modulated Proteins of the EF-Hand Type with Intracellular and Extracellular Functional Roles. A focused review of myokines as a potential contributor to muscle Muscle-Organ Crosstalk: The Emerging Roles of Myokines However, although our understanding of molecular mechanisms regulating muscle atrophy/muscle weakness has substantially progressed, there is no specific treatment for muscle atrophy. One of the most interesting scenarios to test this hypothesis is muscle ageing known as sarcopenia. 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. The role of myokines. S100B-RAGE Dependent VEGF Secretion by Cardiac Myocytes Induces Myofibroblast Proliferation. Chapter 10 Nutrition Metabolism Flashcards | Quizlet Sarcopenia: Revised European Consensus on Definition and Diagnosis. In support of this view, we describe recent ndings on peroxisome pro-liferator-activated receptor gamma coactivator-1 alpha Werner H., Weinstein D., Bentov I. Similarities and Differences between Insulin and IGF-I: Structures, Receptors, and Signalling Pathways. The functional state of the RyR (closed, open, inactivated) largely depends on the intracellular calcium concentration and the state of oxidation of its protein components at particular sites [96]. The myoblasts of sarcopenic subjects release relatively low amounts of S100B, so it could be hypothesized that the high levels of ROS in these cells alter the mechanism of S100B secretion and/or oxidize S100B, which is not secreted and accumulates internally. Nerve Growth Factor Promotes Angiogenesis and Skeletal Muscle Fiber Remodeling in a Murine Model of Hindlimb Ischemia. Examination of the Calcium-Modulated Protein S100 Alpha and Its Target Proteins in Adult and Developing Skeletal Muscle. 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. Int. This protein, which consists of 112 amino acids, is irisin; its amino acid sequence is identical in humans and mice [115]. These include a decrease in the size and number of type II muscle fibers, a sedentary lifestyle, obesity, the presence of metabolic syndrome, reduced plasma concentrations of steroid hormones (androgens) and growth factors and a reduced muscle protein synthesis rate, even in the presence of protein meals or after endurance exercise [19]. Myostatin, on the other hand, appears to have a suppressive effect on skeletal (and cardiac) muscle mass through negative regulation of cellular metabolic processes. However, the effect of NGF on muscle is also expressed through direct actions on tissue trophism because, in mice subjected to thermal stress for different periods of time, a direct correlation between increased expression of the NGF gene and the protective effect on muscle tissue has been demonstrated [61]. The former pathway can also inhibit FoxOs and protein degradation mediated by the ubiquitinproteasome system (UPS). 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]. Although definitive answers are lacking, recent experimental evidence suggests that the mere presence of endogenous stem cells may not be sufficient to ensure muscle regeneration and that the presence of appropriate stimuli and factors as well as protected environments is necessary to provide permissive conditions for stem cell-mediated regeneration [30]. These factors, with molecular weights of 520 kDa, are mainly secreted by skeletal muscle fibers and are capable of exerting many biological effects, either directly on the muscle that has secreted them (autocrine effect) or on tissues located nearby (paracrine effect) or, when transported by the blood, far from the site of production (endocrine effect), affecting complex multi-organ processes such as metabolism, angiogenesis and inflammation [1]. ), 5A&C M-C Foundation for Translational Myology, 35100 Padova, Italy. Chao M.V. In addition, pluripotent cells capable of differentiating into the muscle phenotype are also present in other tissues, such as the heart, bone and, above all, the walls of vessels [7,8,9]. Myokines linked to senescence-related changes. Le Moal E., Pialoux V., Juban G., Groussard C., Zouhal H., Chazaud B., Mounier R. Redox Control of Skeletal Muscle Regeneration. Zhang D., Tan X., Tang N., Huang F., Chen Z., Shi G. Review of Research on the Role of Irisin in Tumors. ROS and myokines promote muscle adaptation to exercise - Cell Press A positive NPB is generally indicative of a positive remodelling response that may be hypertrophic (i.e., increase fibre cross-sectional area) or non-hypertrophic (i.e., increase metabolic quality) in nature, whereas a reduced NPB reflects an obvious phenotype of being negative by inducing a loss of muscle mass or poor metabolic quality. Uchida M.C., Marzetti E. If my muscle could talk: Myokines as a biomarker of frailty. For these reasons, the current definition of myokines is cytokines and other peptides that are produced, expressed and released by muscle fibers and exert either autocrine, paracrine, or endocrine effects [2]. Licensee MDPI, Basel, Switzerland. However, irisin also appears to have a positive effect on cognitive function and to play a role in bone metabolism regulation [2,123]. HHS Vulnerability Disclosure, Help It has been suggested that sarcopenia may be triggered by reactive oxygen species (ROS) that have accumulated throughout ones lifetime. Inclusion in an NLM database does not imply endorsement of, or agreement with, Antioxidant vitamins C or E may help muscle mass and function . The first is that the evidence accumulated in recent years indicates that insulin-R and IGF-1R are present in the nucleus (but also in the Golgi apparatus) of both normal and transformed cells, and thus, display a range of overlapping activities that fall under the definition of transcription factors [71]. (2018) proposed that in postmenopausal women, the decrease of blood irisin concentration is an independent predictor of sarcopenia [128,129]. However, many other animal and human studies have shown an increase in circulating levels of irisin after exercise. Nuclear Localization and Actions of the Insulin-like Growth Factor 1 (IGF-1) System Components: Transcriptional Regulation and DNA Damage Response. Atrophy is a classical hallmark of an array of disorders that affect skeletal muscle, ranging from inherited dystrophies, acquired inflammatory myopathies, ageing (sarcopenia) and critical illness (sepsis). Myokines: A potential key factor in development, treatment, and Frontiers Media SA, Dec 24, 2020 - Science - 256 pages. The term insulin/IGF resistance describes a phenomenon in which the body exhibits blunted activation of the IR and IGF1R signaling cascades. and transmitted securely. However, no data have been published on this issue, and the statement is, therefore, only a working hypothesis. Irisin, even at lower concentrations (5 nM), stimulates mitochondrial biogenesis by increasing the gene expression of Tfam, Ppargc1a and Nrf1, as well as gene and protein levels of UCP3 and GLUT4, in murine C2C12 cells. Huh J.Y., Mougios V., Kabasakalis A., Fatouros I., Siopi A., Douroudos I.I., Filippaios A., Panagiotou G., Park K.H., Mantzoros C.S. Flori L., Testai L., Calderone V. The Irisin System: From Biological Roles to Pharmacological and Nutraceutical Perspectives. Physical activity is considered one of the main strategies to counteract muscle decline in the elderly. Shabani F., Farasat A., Mahdavi M., Gheibi N. Calprotectin (S100A8/S100A9): A Key Protein between Inflammation and Cancer. The aim of this review is to describe in detail a number of myokines that are, to varying degrees, involved in skeletal muscle aging processes and belong to the group of proteins present in the functional environment surrounding the muscle cell known as the Niche. Antimyostatin Treatment in Health and Disease: The Story of Great Expectations and Limited Success. Fig. Reducing the insulin/IGF1 receptor pathway, well known to promote longevity, also improves sarcopenia [22]. Vechetti I.J., Valentino T., Mobley C.B., McCarthy J.J. Riuzzi F., Sorci G., Sagheddu R., Chiappalupi S., Salvadori L., Donato R. RAGE in the Pathophysiology of Skeletal Muscle. This resulted in the classic dogma that prevailed for many years in the field, which attributed a mainly metabolic role to the insulin/IR system and a mitogenic, proliferative/differentiative role to the IGF/IGFR system [70]. As a library, NLM provides access to scientific literature. Indeed, Ettinger et al. They also hypothesized that, under stress conditions, the level of NGF increases with consequent autocrine activation of the muscle and increased survival/myoprotection [55]. 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. Regulation of PPARGC1A Gene Expression in Trained and Untrained Human Skeletal Muscle. In more recent experimental clinical studies in humans, a direct association between Sirt-1 levels and PGC1/irisin expression was found in obese patients or those with type 2 diabetes [117]. If CREB is inhibited, FNDC5 transcription is suppressed [116]. 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]. Satellite cells of sarcopenic muscle and proliferating aged myoblasts accumulate ROS due to altered mitochondrial homeostasis and impaired antioxidant systems [107]. Animal Models of Sarcopenia. Exercise-induced myokines in health and metabolic diseases 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]. A. Davies A.M. Unfortunately, this homeostatic system tends to become less efficient with age, first in males and then in females, and in the skeletal muscle overall, ROS accumulate in the tissue, where these reactive elements are usually quite harmful and can damage other cellular components, such as DNA, contractile proteins and membrane lipids. Yang X.-Y., Tse M.C.L., Hu X., Jia W.-H., Du G.-H., Chan C.B. Costamagna D., Berardi E., Ceccarelli G., Sampaolesi M. Adult Stem Cells and Skeletal Muscle Regeneration. During the past decade, skeletal muscle has been considered to function as an autocrine, paracrine, and endocrine organ by releasing numerous myokines. Franzini-Armstrong C., Protasi F. Ryanodine Receptors of Striated Muscles: A Complex Channel Capable of Multiple Interactions. The use of animal model organisms, such as mice, rats, flies and worms, has advanced the field of sarcopenia research, enabling the identification of some therapeutic strategies and/or dietary and lifestyle behaviors that result in improved muscle mass and function in old animals [20].