Abstract:Skeletal muscle adaptation to exercise training is a consequence of repeated contraction-induced increases in gene expression that lead to the accumulation of functional proteins whose role is to blunt the homeostatic perturbations generated by escalations in energetic demand and substrate turnover. The development of a specific 'exercise phenotype' is the result of new, augmented steady-state mRNA and protein levels that stem from the training stimulus (i.e. endurance or resistance based). Maintaining appropr… Show more
“…It has been shown that AICR activates AMPK by acting as an AMP mimetic that binds to AMP binding sites on intracellular proteins, thus leading to metabolic stress 32 . Exercise-induced AMPK activation also causes metabolic stress, but it simultaneously increases mechanical stress 60 . The reasons for the differences in therapeutic effects between AICAR and exercise are that the mechanical stress is only caused by exercise.…”
Idiopathic inflammatory myopathies cause progressive muscle weakness and degeneration. Since high-dose glucocorticoids might not lead to full recovery of muscle function, physical exercise is also an important intervention, but some exercises exacerbate chronic inflammation and muscle fibrosis. It is unknown how physical exercise can have both beneficial and detrimental effects in chronic myopathy. Here we show that senescence of fibro-adipogenic progenitors (FAPs) in response to exercise-induced muscle damage is needed to establish a state of regenerative inflammation that induces muscle regeneration. In chronic inflammatory myopathy model mice, exercise does not promote FAP senescence or resistance against tumor necrosis factor-mediated apoptosis. Pro-senescent intervention combining exercise and pharmacological AMPK activation reverses FAP apoptosis resistance and improves muscle function and regeneration. Our results demonstrate that the absence of FAP senescence after exercise leads to muscle degeneration with FAP accumulation. FAPtargeted pro-senescent interventions with exercise and pharmacological AMPK activation may constitute a therapeutic strategy for chronic inflammatory myopathy.
“…It has been shown that AICR activates AMPK by acting as an AMP mimetic that binds to AMP binding sites on intracellular proteins, thus leading to metabolic stress 32 . Exercise-induced AMPK activation also causes metabolic stress, but it simultaneously increases mechanical stress 60 . The reasons for the differences in therapeutic effects between AICAR and exercise are that the mechanical stress is only caused by exercise.…”
Idiopathic inflammatory myopathies cause progressive muscle weakness and degeneration. Since high-dose glucocorticoids might not lead to full recovery of muscle function, physical exercise is also an important intervention, but some exercises exacerbate chronic inflammation and muscle fibrosis. It is unknown how physical exercise can have both beneficial and detrimental effects in chronic myopathy. Here we show that senescence of fibro-adipogenic progenitors (FAPs) in response to exercise-induced muscle damage is needed to establish a state of regenerative inflammation that induces muscle regeneration. In chronic inflammatory myopathy model mice, exercise does not promote FAP senescence or resistance against tumor necrosis factor-mediated apoptosis. Pro-senescent intervention combining exercise and pharmacological AMPK activation reverses FAP apoptosis resistance and improves muscle function and regeneration. Our results demonstrate that the absence of FAP senescence after exercise leads to muscle degeneration with FAP accumulation. FAPtargeted pro-senescent interventions with exercise and pharmacological AMPK activation may constitute a therapeutic strategy for chronic inflammatory myopathy.
“…Nutrient and energy availability play an important role in the modulation of acute and chronic adaptations to both endurance and resistance training, 64 suggesting that an adequate nutritional support should be provided to patients in order to preserve the potential benefits of exercise. 62
Vice versa , unloading blunts the amino acid-induced increase in myofibrillar protein synthesis, further supporting the concept that nutrition and exercise may have potential additive effects, 65 although this aspect deserves further investigation in cancer cachexia.…”
Section: Options For Prevention and Treatmentmentioning
Cancer cachexia is a severe and disabling clinical condition that frequently accompanies the development of many types of cancer. Muscle wasting is the hallmark of cancer cachexia and is associated with serious clinical consequences such as physical impairment, poor quality of life, reduced tolerance to treatments and shorter survival. Cancer cachexia may evolve through different stages of clinical relevance, namely pre-cachexia, cachexia and refractory cachexia. Given its detrimental clinical consequences, it appears mandatory to prevent and/or delay the progression of cancer cachexia to its refractory stage by implementing the early recognition and treatment of the nutritional and metabolic alterations occurring during cancer. Research on the molecular mechanisms underlying muscle wasting during cancer cachexia has expanded in the last few years, allowing the identification of several potential therapeutic targets and the development of many promising drugs. Several of these agents have already reached the clinical evaluation, but it is becoming increasingly evident that a single therapy may not be completely successful in the treatment of cancer-related muscle wasting, given its multifactorial and complex pathogenesis. This suggests that early and structured multimodal interventions (including targeted nutritional supplementation, physical exercise and pharmacological interventions) are necessary to prevent and/or treat the devastating consequences of this cancer comorbidity, and future research should focus on this approach.
“…Exercise alters human homeostasis by different means, with energy metabolism particularly affected by heavy and strenuous activities. From a substantial increase in an expenditure of cellular energy to an up-regulation of proteins involved in all aspects of energy turnover (Smiles et al, 2016), exhaustive exercise is consistently accompanied by considerable changes in various indicators of energy metabolism in the circulation and energy-demanding tissues, such as the brain, heart, or skeletal muscle (Kastellorizios and Burgess, 2015). Specifically, a plethora of blood-based biomarkers have emerged in recent years as effective screening tools used to monitor exhaustive exercise-induced changes in bioenergetics (Lee et al, 2017).…”
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