Publishers Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Riuzzi F., Sorci G., Sagheddu R., Chiappalupi S., Salvadori L., Donato R. RAGE in the Pathophysiology of Skeletal Muscle. ROS imbalance occurs in myofibers, causing metabolic events that lead to an imbalance in protein synthesis with the onset of muscle atrophy. Stuerenburg H.J., Kunze K. Tissue Concentrations of Nerve Growth Factor in Aging Rat Heart and Skeletal Muscle. However, it must be recalled that muscle mass is an important factor influencing circulating irisin concentrations, and the difference in muscle mass between subjects may also be a reason for the divergence in research results. Skeletal Muscle Recovery from Disuse Atrophy: Protein Turnover Signaling and Strategies for Accelerating Muscle Regrowth. The myokines characterized in this review were selected on the basis of two key 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 and the modulation of the ROS balance in fibers involved in regulatory processes (metabolic or regenerative) of muscle aging. Donato R. S100: A Multigenic Family of Calcium-Modulated Proteins of the EF-Hand Type with Intracellular and Extracellular Functional Roles. Schmidt M., Schler S.C., Httner S.S., von Eyss B., von Maltzahn J. The large presence of these proteins, which can act as powerful mediators of signaling to other cells and tissues, highlights the important role of skeletal muscle as a prominent secretory organ. Int. Targeting Age-Dependent Functional and Metabolic Decline of Human Reviews aren't verified, but Google checks for and removes fake content when it's identified. and transmitted securely. 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]. Flori L., Testai L., Calderone V. The Irisin System: From Biological Roles to Pharmacological and Nutraceutical Perspectives. If this is also true for muscle cells, then S100 may not only have the previously described role in the modulation of RYR but also intervene in one of the key processes of muscle senescence: the regenerative capacity of staminal cells. increased visceral adiposity and muscle atrophy. muscle is an endocrine organ that produces and releases cytokines, termed 'myokines' [12-15] (Box 1). Muscle Stem Cells in Development, Regeneration, and Disease. As a result, these muscles are better protected against stress and sarcopenia [64]. Nerve Growth Factor Promotes Angiogenesis and Skeletal Muscle Fiber Remodeling in a Murine Model of Hindlimb Ischemia. Amano T., Yamakuni T., Okabe N., Sakimura K., Takahashi Y. Satellite cells, quiescent under resting conditions, become activated, expand and differentiate during skeletal muscle regeneration in a process controlled by the expression of Pax genes and sequential expression of myogenic regulatory factors: MyoD, Myf5, Myogenin and MRF4 [6]. The Potential of Endurance Exercise-Derived Exosomes to Treat Metabolic Diseases. Inclusion in an NLM database does not imply endorsement of, or agreement with, 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]. An Overview About the Biology of Skeletal Muscle Satellite Cells. Mapping mammalian biochemistry is a sizable task, and much of that biochemistry remains poorly understood and categorized. Biochemistry and Biology of GDF11 and Myostatin: Similarities, Differences, and Questions for Future Investigation. In vitro experiments performed on H9c2 cardiomyocytes to mimic myocardial remodeling also showed that irisin treatment in the presence of H2O2 attenuated intracellular ROS levels and cardiomyocyte apoptosis in a dose-dependent manner. Collectively, these results seem to indicate that irisin serves as a novel approach to elicit cardioprotection, which is associated with improved mitochondrial function [136]. Conversely, it has also been shown that circulating irisin levels increase with increasing fat mass, particularly in obesity. Vaughan R.A., Gannon N.P., Mermier C.M., Conn C.A. Huh J.Y., Mougios V., Kabasakalis A., Fatouros I., Siopi A., Douroudos I.I., Filippaios A., Panagiotou G., Park K.H., Mantzoros C.S. Erck C., Meisinger C., Grothe C., Seidl K. Regulation of Nerve Growth Factor and Its Low-Affinity Receptor (p75NTR) during Myogenic Differentiation. For example, in vitro exercise-mimicking treatment with forskolin and ionomycin in primary human muscle cell cultures stimulated PGC1 expression but decreased FNDC5 expression and irisin secretion [148]. 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. Garca-Prat L., Martnez-Vicente M., Perdiguero E., Ortet L., Rodrguez-Ubreva J., Rebollo E., Ruiz-Bonilla V., Gutarra S., Ballestar E., Serrano A.L., et al. All authors have read and agreed to the published version of the manuscript. However, irisin also appears to have a positive effect on cognitive function and to play a role in bone metabolism regulation [2,123]. The only data related to the presence of specific myokine binding sites were obtained from experiments on bone cells, one of the primary targets for irisin and a likely paracrine site of its action. Based on clinical observations, some authors have hypothesized that an excess of irisin could lead to mitochondrial dysfunction and cardiomyocyte damage. This eBook is a collection of articles from a Frontiers Research Topic. Circulating Irisin Levels Are Positively Associated with Metabolic Risk Factors in Sedentary Subjects. In addition, such tissue has a high . A focused review of myokines as a potential contributor to muscle Panati K., Narala V.R., Narasimha V.R., Derangula M., Arva Tatireddigari V.R.R., Yeguvapalli S. Expression, Purification and Biological Characterisation of Recombinant Human Irisin (12.5 kDa). The Ever-Expanding Myokinome: Discovery Challenges and Therapeutic Implications. Studies in humans and rodents have reported that myokines are important mediators of the physical benefits of exercise and . Table 1 summarizes the principal information on the selected myokines. Pietrangelo T., Puglielli C., Mancinelli R., Beccafico S., Fan G., Fulle S. Molecular Basis of the Myogenic Profile of Aged Human Skeletal Muscle Satellite Cells during Differentiation. They were recently shown to have different types of myogenic cells, all of which have exceptional regenerative potential. This second event, in turn, may be due either to increased protein degradation through enhanced proteasomal and lysosomal activity via activation of FOXO-3 signaling or to reduced protein synthesis regulated mainly by the PI3K/AKT pathway [3]. This fine-tuning occurs at specific common RyR sites through interaction with two calcium-binding regulatory proteins present in the sarcoplasm and reticulum membranes, respectively: Calmodulin and S100A [97]. Sarcopenia: Revised European Consensus on Definition and Diagnosis. 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 . Shi L., Zhao Y., Fei C., Guo J., Jia Y., Wu D., Wu L., Chang C. Cellular Senescence Induced by S100A9 in Mesenchymal Stromal Cells through NLRP3 Inflammasome Activation. Homage to Rita Levi-Montalcini, the Queen of Modern Neuroscience: Homage to Rita Levi-Montalcini. Goals / Objectives Muscle is an endocrine organ and it influences itself in an autocrine/paracrine fashion via synthesis and release of myokines. These effects can increase the risk of . Nielsen T.L., Vissing J., Krag T.O. Characterization of the Metabolic Effects of Irisin on Skeletal Muscle in Vitro. The myokine Fibcd1 is an endogenous determinant of myofiber - Nature following vitamin D treatment associates with IL-6 systemic suppression and results in significant improvement of muscle atrophy [125,126]. In addition, the presence of oxidative stress in the skeletal muscle plays a significant role in the progression of sarcopenia because it leads to a substantial reduction in the regenerative potential of muscle fibers linked to the recruitment of quiescent satellite cells, as shown in Figure 1 [26]. Indeed, ROS have an established role in muscle Do ROS induce mitochondria and antioxidant defense mechanisms? 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. During aging, the ability of skeletal muscle to sustain an efficient regenerative pathway is severely impaired, despite the presence of a reduced, even if apparently normal, pool of satellite cells [29]. The exercising muscle requires increased mitochondrial respiration, which subsequently results in elevated ROS production and induced antioxidant defense mechanisms (Figure 1). Bostrm P., Wu J., Jedrychowski M.P., Korde A., Ye L., Lo J.C., Rasbach K.A., Bostrm E.A., Choi J.H., Long J.Z., et al. Finally, IGF-IRs have a broad spectrum of cross-talk with many other tyrosine kinase receptors [74]. They have autocrine, paracrine and/or endocrine effects; their systemic effects occur at picomolar concentrations.. Receptors for myokines are found on muscle, fat, liver . Davies A.M. 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 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]. Raschke S., Elsen M., Gassenhuber H., Sommerfeld M., Schwahn U., Brockmann B., Jung R., Wislff U., Tjnna A.E., Raastad T., et al. In particular, it was found that the levels of NGF in rat heart muscle were significantly higher than in skeletal muscle, but a cause/effect relationship based on age between the muscle concentration of the growth factor and the trophic state of the examined animal was not established [51]. Zimmer D.B. Cell.
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