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Myokines released by exercise are identified as factors that can influence a person's health and wellbeing. While myokine secretion in response to an acute bout of endurance and resistance-type exercise has been examined, the influence of resistance-exercise training on myokines at rest is less well established. Therefore, this study was designed to evaluate a panel of myokines at rest following a 12-week resistance-exercise training program in younger and older males. Participants (n = 15) completed a 12-week progressive resistance-exercise training program supervised by a certified fitness professional. The training protocol targeted all major muscle groups of the upper and lower body. Resting blood samples were collected before and after completion of the training program to determine concentrations of apelin, fibroblast growth factor-21 (FGF-21), interleukin (IL)-4, IL-6, IL-7, IL-15, leukemia inhibitory factor (LIF), and irisin. Two-way repeated ANOVAs were used to compare variables between time-points and age groups. There was a main effect of time found for apelin (p = 0.003) and IL-15 (p < 0.001), while no main effects for group or time were found for the other myokines (all p > 0.05). Age group × training status interactions were found for IL-6 (p = 0.04) and irisin (p = 0.014) without pairwise differences for IL-6 (p > 0.05), and younger males had higher concentrations of irisin compared to older males post-training (p = 0.036). Overall, the 12-week resistance-exercise training program significantly increased apelin and IL-15 over time but did not change the other resting myokine concentrations for the younger or older males. However, the higher concentration of irisin in younger versus older males post-training suggests a potential explanation for the anabolic resistance observed with aging. [ABSTRACT FROM AUTHOR]

Mechanical perturbation triggers activation of resident myogenic stem cells to enter the cell cycle through a cascade of events including hepatocyte growth factor (HGF) release from its extracellular tethering and the subsequent presentation to signaling‐receptor c‐met. Here, we show that with aging, extracellular HGF undergoes tyrosine‐residue (Y) nitration and loses c‐met binding, thereby disturbing muscle homeostasis. Biochemical studies demonstrated that nitration/dysfunction is specific to HGF among other major growth factors and is characterized by its locations at Y198 and Y250 in c‐met‐binding domains. Direct‐immunofluorescence microscopy of lower hind limb muscles from three age groups of rat, provided direct in vivo evidence for age‐related increases in nitration of ECM‐bound HGF, preferentially stained for anti‐nitrated Y198 and Y250‐HGF mAbs (raised in‐house) in fast IIa and IIx myofibers. Overall, findings highlight inhibitory impacts of HGF nitration on myogenic stem cell dynamics, pioneering a cogent discussion for better understanding age‐related muscle atrophy and impaired regeneration with fibrosis (including sarcopenia and frailty). [ABSTRACT FROM AUTHOR]

This document is the cover legend for an article titled "Age-related nitration/dysfunction of myogenic stem cell activator HGF" published in the journal Aging Cell. The article, authored by Alaa Elgaabari et al., explores the impact of aging on the function of a protein called HGF, which is involved in the activation of stem cells responsible for muscle regeneration. The research suggests that age-related nitration of HGF may contribute to the decline in muscle regeneration observed in older individuals. The article includes a list of all the authors involved in the study. [Extracted from the article]

Satellite cells (SCs), stem cells in skeletal muscle, are mitotically quiescent in adult mammals until activated for growth or regeneration. In mouse muscle, SCs are activated by nitric oxide (NO), hepatocyte growth factor (HGF) and the mechanically induced NO-HGF signaling cascade. Here, the SC population on fibers from the adult, ectothermic zebrafish and SC responsiveness to activating stimuli were assessed using the model system of isolated fibers cultured at 27 and 21°C. SCs were identified by immunostaining for the HGF receptor, c-met, and activation was determined using bromodeoxyuridine uptake in culture or in vivo. In dose-response studies, SC activation was increased by treatment with the NO-donor drug isosorbide dinitrate (1 mmol l-1) or HGF (10 ng ml-1) to maximum activation at lower concentrations of both than in previous studies of mouse fibers. HGF-induced activation was blocked by anti-c-met antibody, and reduced by culture at 21°C. The effect of cyclical stretch (3 h at 4 cycles per minute) increased activation and was blocked by nitric oxide synthase inhibition and reduced by culture at 21°C. The number of c-met+ SCs per fiber increased rapidly (by 3 h) after stretching. The character of signaling in SC activation on zebrafish fibers, in particular temperature-dependent responses to HGF and stretch, gives new insights into the influence of ectothermy on regulation of muscle growth in teleosts and suggests the use of the single-fiber model system to explore the basis of fiber hyperplasia and the conservation of regulatory pathways between species. [ABSTRACT FROM AUTHOR]

Background: Knee osteoarthritis (OA) is the most prevalent medical condition in individuals over the age of 65 years, and is a progressive joint degenerative condition with no known cure. Research suggests that there is a strong relationship between knee pain and loss of physical function. The resulting lifestyle modifications negatively impact not only disease onset and progression but also overall health, work productivity, and quality of life of the affected individual. Purpose: The goal of this investigation was to examine the feasibility of using an emerging technology called lower body positive pressure (LBPP) to simulate weight loss and reduce acute knee pain during treadmill walking exercise in overweight individuals with radiographically confirmed symptomatic knee OA. Design: Prospective case series. Methods: Twenty-two overweight individuals with knee OA completed two 20-minute treadmill walking sessions (one full weight bearing and one LBPP supported) at a speed of 3.1 mph, 0% incline. Acute knee pain was assessed using a visual analog scale, and the percentage of LBPP support required to minimize knee pain was evaluated every 5 minutes. Knee Osteoarthritis Outcome Scores were used to quantify knee pain and functional status between walking sessions. The order of testing was randomized, with sessions occurring a minimum of 1 week apart. Results: A mean LBPP of 12.4% of body weight provided participants with significant pain relief during walking, and prevented exacerbation of acute knee pain over the duration of the 20-minute exercise session. Patients felt safe and confident walking with LBPP support on the treadmill, and demonstrated no change in Knee Osteoarthritis Outcome Scores over the duration of the investigation. Conclusion: Results suggest that LBPP technology can be used safely and effectively to simulate weight loss and reduce acute knee pain during weight-bearing exercise in an overweight knee OA patient population. These results could have important implications for the development of future treatment strategies used in the management of at-risk patients with progressive knee OA. [ABSTRACT FROM AUTHOR]

When skeletal muscle is stretched or injured, satellite cells, resident myogenic stem cells positioned beneath the basal lamina of mature muscle fibers, are activated to enter the cell cycle. This signaling pathway is a cascade of events including calcium-calmodulin formation, nitric oxide (NO) radical production by NO synthase, matrix metalloproteinase activation, release of hepatocyte growth factor (HGF) from the extracellular matrix, and presentation of HGF to the receptor c-met, as demonstrated by assays of primary cultures and in vivo experiments. Here, we add evidence that two ion channels, the mechanosensitive cation channel (MS channel) and the long-lasting-type voltage-gated calcium-ion channel (L-VGC channel), mediate the influx of extracellular calcium ions in response to cyclic stretch in satellite cell cultures. When applied to 1-h stretch cultures with individual inhibitors for MS and L-VGC channels (GsMTx-4 and nifedipine, respectively) or with a less specific inhibitor (gadolinium chloride, Gd), satellite cell activation and upstream HGF release were abolished, as revealed by bromodeoxyuridine-incorporation assays and Western blotting of conditioned media, respectively. The inhibition was dose dependent with a maximum at 0.1 μM (GsMTx-4), 10 μM (nifedipine), or 100 μM (Gd) and canceled by addition of HGF to the culture media; a potent inhibitor for transient-type VGC channels (NNC55-0396, 100 μM) did not show any significant inhibitory effect. The stretch response was also abolished when calcium-chelator EGTA (1.8 mM) was added to the medium, indicating the significance of extracellular free calcium ions in our present activation model. Finally, cation/calcium channel dependencies were further documented by calcium-imaging analyses on stretched cells; results clearly demonstrated that calcium ion influx was abolished by GsMTx-4, nifedipine, and EGTA. Therefore, these results provide an additional insight that calcium ions may flow in through L-VGC channels by possible coupling with adjacent MS channel gating that promotes the local depolarization of cell membranes to initiate the satellite cell activation cascade. [ABSTRACT FROM AUTHOR]

In Duchenne muscular dystrophy (DMD), palliative glucocorticoid therapy can produce myopathy or calcification. Since increased nitric oxide synthase activity in dystrophic mice promotes regeneration, the outcome of two nitric oxide (NO) donor drugs, MyoNovin (M) and isosorbide dinitrate (I), on the effectiveness of the anti-inflammatory drug prednisone (P) in alleviating progression of dystrophy was tested. Dystrophic mdx mice were treated (18 days) as controls or with an NO donor ± P. Fiber permeability and DNA synthesis were labeled by Evans blue dye (EBD) and bromodeoxyuridine uptake, respectively. P decreased body weight gain, M increased quadriceps mass, and I increased heart mass. P increased fiber permeability (%EBD+ fibers) and calcification in diaphragm. Treatment with NO donors + P (M+P, I+P) reduced %EBD+ fibers and calcification vs. P alone. %EBD+ fibers in M+P diaphragm did not differ from control. NO donor treatment reduced proliferation and the population of c-met+ cells and accelerated fiber regeneration. Concurrent with P, NO donor treatment suppressed two important detrimental effects of P in mice, possibly by accelerating regeneration, rebalancing satellite cell quiescence and activation in dystrophy, and/or increasing perfusion. Results suggest that NO donors could improve current therapy for DMD. [ABSTRACT FROM AUTHOR]

Satellite cells are companions to voluntary muscle fibres, and are named for their intimate positional or 'satellite' relationship, as if revolving around fibres, like a satellite moon around the earth. Studies on the nature of at least some satellite cells, including their capabilities for self-renewal and for giving rise to multiple lineages in a stem cell-like function, are exploring the molecular basis of phenotypes described by markers of specialized function and gene expression in normal development, neuromuscular disease and aging. In adult skeletal muscle, the self-renewing capacity of satellite cells contributes to muscle growth, adaptation and regeneration. Muscle remodeling, such as demonstrated by changes in myofibre cross-sectional area and length, nerve and tendon junctions, and fibre-type distribution, occur in the absence of injury and provide broad functional and structural diversity among skeletal muscles. Those contributions to plasticity involve the satellite cell in at least five distinct roles, here described using metaphors for behaviour or the investigator's perspective. Satellite cells are the 'currency' of muscle; have a 'conveyance' role in adaptation by domains of cytoplasm along a myofibre; serve researchers, through a marker role, as 'clues' to various activities of muscle; are 'connectors' that physically, and through signalling and cell-fibre communications, bridge myofibres to the intra- and extra-muscular environment; and are equipped as metabolic and genetic filters or 'colanders' that can rectify or modulate particular signals. While all these roles are still under exploration, each contributes to the plasticity of skeletal muscle and thence to the overall biology and function of an organism. The use of metaphor for describing these roles helps to clarify and scrutinize the definitions that form the basis of our understanding of satellite cell biology: the metaphors provide the construct for various approaches to detect or test the nature of satellite cell functions in skeletal muscle plasticity. [ABSTRACT FROM AUTHOR]

Our previous studies demonstrated that an 8-week intake of 5% (w/w) apple polyphenol (APP) in the diet improves muscle endurance of young-adult rats. In order to identify a lower limit of the dietary contribution of APP to the effect, the experiments were designed for lower-dose supplementation (8-week feeding of 0.5% APP in AIN-93G diet) to 12-week-old male Sprague-Dawley rats. Results clearly showed that the 0.5% APP diet significantly up-regulates slower myosin-heavy-chain (MyHC) isoform ratios (IIx and IIa relative to total MyHC) and myoglobin expression in lower hind-limb muscles examined ( P < 0.05). There was a trend to increased fatigue resistance detected from measurements of relative isometric plantar-flexion force torque generated by a stimulus train delivered to the tibial nerve ( F(98, 1372) = 1.246, P = 0.0574). Importantly, there was no significant difference in the animal body-phenotypes or locomotor activity shown as total moving distance in light and dark periods. Therefore, the present study encourages the notion that even low APP-intake may increase the proportions of fatigue-resistant myofibers, and has promise as a strategy for modifying performance in human sports and improving function in age-related muscle atrophy. [ABSTRACT FROM AUTHOR]

Comments on the findings of study in Caenorhabditis elegans indicating that genetic defects in acetylcholine (AchE) transmission at the neuromuscular junction (NMJ) might partially underlie Duchenne Muscular Dystrophy (DMD). Identification of mutations in the dystrophin gene as the cause of DMD; Reduction in AchE activity in dys-1 mutants; Relevance of cholinergic transmission at the NMJ in mammalian dystrophies.