Changes in muscle mass may result from changes in protein turnover, reflecting the balance between protein synthesis and protein degradation, and changes in cell turnover, reflecting the balance between myonuclear accretion and myonuclear loss. Myonuclear accretion, i.e. increase in the number of myonuclei within the muscle fibers, takes place via proliferation and fusion of satellite cells, myogenic stem cells associated to skeletal muscle fibers and involved in muscle regeneration. In developing muscle, satellite cells undergo extensive proliferation and most of them fuse with myofibers, thus contributing to the increase in myonuclei during early postnatal stages. A similar process is induced in adult skeletal muscle by functional overload and exercise. In contrast, satellite cells and myonuclei may undergo apoptosis during muscle atrophy, although it is debated whether myonuclear loss occurs in atrophying muscle. An increase in myofiber size can also occur by changes in protein turnover without satellite cell activation, e.g. in late phases of postnatal development or in some models of muscle hypertrophy. The relative role of protein turnover and cell turnover in muscle adaptation and in the establishment of functional muscle hypertrophy remains to be established. The identification of the signaling pathways mediating satellite cell activation may provide therapeutic targets for combating muscle wasting in a variety of pathological conditions, including cancer cachexia, renal and cardiac failure, neuromuscular diseases, as well as aging sarcopenia.
"Muscle growth involves a tightly controlled balance between protein synthesis and degradation . Protein synthesis is driven by the growth hormone (GH)/Insulin like growth factor (IGF)/mammalian target of rapamycin (mTOR) pathway [2-5], whereas protein degradation occurs via a number of pathways including ubiquitin proteasome [6-8], lysosomal , apoptotic  and the calcium dependant calpains . "
[Show abstract][Hide abstract] ABSTRACT: The relationship between fish health and muscle growth is critical for continued expansion of the aquaculture industry. The effect of immune stimulation on the expression of genes related to the energy balance of fish is poorly understood. In mammals immune stimulation results in major transcriptional changes in muscle, potentially to allow a reallocation of amino acids for use in the immune response and energy homeostasis. The aim of this study was to investigate the effects of immune stimulation on fish muscle gene expression.
Atlantic salmon (Salmo salar) primary muscle cell cultures were stimulated with recombinant (r)IL-1beta, a major proinflammatory cytokine, for 24 h in order to simulate an acute immune response. The transcriptomic response was determined by RNA hybridization to a 4 x 44 K Agilent Atlantic salmon microarray platform. The rIL-1beta stimulation induced the expression of genes related to both the innate and adaptive immune systems. In addition there were highly significant changes in the expression of genes related to regulation of the cell cycle, growth/structural proteins, proteolysis and lipid metabolism. Of interest were a number of IGF binding proteins that were differentially expressed, which may demonstrate cross talk between the growth and immune systems.
We show rIL-1beta modulates the expression of not only immune related genes, but also that of genes involved in processes related to growth and metabolism. Co-stimulation of muscle cells with both rIGF-I and rIL-1beta demonstrates cross talk between these pathways providing potential avenues for further research. This study highlights the potential negative effects of inflammation on muscle protein deposition and growth in fish and extends our understanding of energy allocation in ectothermic animals.
"Analysis of the contractility of single fibers from MSTN null mice demonstrated that the specific force deficits were at the level of the muscle myofiber [80,81▪▪]. Historically, it has been thought that a major function of myostatin was to maintain muscle satellite cell quiescence and that the relief of this inhibitory influence led to satellite proliferation and fusion to existing myofibers resulting in hypertrophy, akin to the mechanisms of muscle enlargement after exercise [81▪▪,82]. However, recent evidence demonstrates that myostatin exerts its effects directly on the myofiber with little effect on satellite cell activity [83▪]. "
[Show abstract][Hide abstract] ABSTRACT: This review summarizes recent progress in the development of myostatin inhibitors for the treatment of muscle wasting disorders. It also focuses on findings in myostatin biology that may have implications for the development of antimyostatin therapies.
There has been progress in evaluating antimyostatin therapies in animal models of muscle wasting disorders. Some programs have progressed into clinical development with initial results showing positive impact on muscle volume.In normal mice myostatin deficiency results in enlarged muscles with increased total force but decreased specific force (total force/total mass). An increase in myofibrillar protein synthesis without concomitant satellite cell proliferation and fusion leads to muscle hypertrophy with unchanged myonuclear number. A specific force reduction is not observed when atrophied muscle, the predominant therapeutic target of myostatin inhibitor therapy, is made myostatindeficient.Myostatin has been shown to be expressed by a number of tumor cell lines in mice and man.
Myostatin inhibition remains a promising therapeutic strategy for a range of muscle wasting disorders.This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivitives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by-nc-nd/3.0.
Current opinion in supportive and palliative care 10/2013; 7(4). DOI:10.1097/SPC.0000000000000013 · 1.66 Impact Factor
"Satellite cells in muscle disease therapy and future perspectives Sarcopenia, the loss of muscle fibers at an advanced age, is one of the major causes for falls and subsequently health deterioration in the elderly. The underlying reason for the reduced muscle mass is not entirely clear, and the contribution of age-related changes in satellite stem cell is under debate (Pallafacchina et al. 2012; Shadrach and Wagers 2011). Most other muscle diseases including the muscular dystrophies are genetic disorders associated with progressive muscle weakness and degeneration. "
[Show abstract][Hide abstract] ABSTRACT: Aging is accompanied by reduced regenerative capacity of all tissues and organs and dysfunction of adult stem cells. Notably, these age-related alterations contribute to distinct pathophysiological characteristics depending on the tissue of origin and function and thus require special attention in a type by type manner. In this paper, we review the current understanding of the mechanisms leading to tissue-specific adult stem cell dysfunction and reduced regenerative capacity with age. A comprehensive investigation of the hematopoietic, the neural, the mesenchymal, and the skeletal stem cells in age-related research highlights that distinct mechanisms are associated with the different types of tissue stem cells. The link between age-related stem cell dysfunction and human pathologies is discussed along with the challenges and the future perspectives in stem cell-based therapies in age-related diseases.
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