Skeletal muscle mass, a strong predictor of longevity and health in humans, is determined by the balance of two cellular processes, muscle protein synthesis (MPS) and muscle protein breakdown. MPS seems to be particularly sensitive to changes in mechanical load and/or nutritional status; therefore, much research has focused on understanding the molecular mechanisms that underpin this cellular process. Furthermore, older individuals display an attenuated MPS response to anabolic stimuli, termed anabolic resistance, which has a negative impact on muscle mass and function, as well as quality of life. Therefore, an understanding of which, if any, molecular mechanisms contribute to anabolic resistance of MPS is of vital importance in formulation of therapeutic interventions for such populations. This review summarizes the current knowledge of the mechanisms that underpin MPS, which are broadly divided into mechanistic target of rapamycin complex 1 (mTORC1)-dependent, mTORC1-independent, and ribosomal biogenesis-related, and describes the evidence that shows how they are regulated by anabolic stimuli (exercise and/or nutrition) in healthy human skeletal muscle. This review also summarizes evidence regarding which of these mechanisms may be implicated in age-related skeletal muscle anabolic resistance and provides recommendations for future avenues of research that can expand our knowledge of this area.
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http://dx.doi.org/10.1152/ajpcell.00209.2019 | DOI Listing |
Angew Chem Int Ed Engl
December 2024
Wuhan University College of Chemistry and Molecular Sciences, Bayi Road 299, Wuhan, CHINA.
Real-time monitoring of reactive oxygen and nitrogen species (RONS) in skeletal muscle provides crucial insights into the cause-and-effect relationships between physical activity and health benefits. However, the dynamic production of exercise-induced RONS remains poorly explored, due to the lack of sensing tools that can conform to soft skeletal muscle while monitor RONS release during exercise. Here we introduce dual flexible sensors via twisting carbon nanotubes into helical bundles of fibers and subsequent assembling electrochemical sensing components.
View Article and Find Full Text PDFFASEB J
December 2024
Systems Engineering and Science, Graduate School of Engineering and Science, Shibaura Institute of Technology, Saitama, Japan.
Flavan-3-ols (FL) are poorly bioavailable astringent polyphenols that induce hyperactivation of the sympathetic nervous system. The aim of this study was to investigate the effects of repeated oral administration of FL on mice hindlimb skeletal muscle using immunohistochemical techniques. C57BL/6J male mice were orally administered 50 mg/kg of FL for a period of 2 weeks, and bromideoxyuridine (BrdU) was administered intraperitoneally 3 days prior to the dissection.
View Article and Find Full Text PDFMuscle Nerve
December 2024
AMRA Medical AB, Linköping, Sweden.
Introduction/aims: Improved methodologies to monitor the progression of Duchenne muscular dystrophy (DMD) are needed, especially in the context of clinical trials. We report changes in muscle magnetic resonance imaging (MRI) parameters in participants with DMD, including changes in lean muscle volume (LMV), muscle fat fraction (MFF), and muscle fat infiltration (MFI) and their relationship to changes in functional parameters.
Methods: MRI data were obtained as part of a clinical study (NCT02310763) of domagrozumab, an antibody-targeting myostatin that negatively regulates skeletal muscle mass.
Muscle Nerve
December 2024
Aix-Marseille Univ, CNRS, CRMBM, Marseille, France.
Introduction And Aims: Mitochondrial myopathies are rare genetic disorders for which no effective treatment exists. We previously showed that the pharmacological cyclophilin inhibitor cyclosporine A (CsA) extends the lifespan of fast-twitch skeletal muscle-specific mitochondrial transcription factor A knockout (Tfam KO) mice, lacking the ability to transcribe mitochondrial DNA and displaying lethal mitochondrial myopathy. Our present aim was to assess whether the positive effect of CsA was associated with improved in vivo mitochondrial energy production.
View Article and Find Full Text PDFGeneration of induced pluripotent cells (hiPSCs)-derived skeletal muscle progenitor cells (SMPCs) holds great promise for regenerative medicine for skeletal muscle wasting diseases, as for example Duchenne Muscular Dystrophy (DMD). Multiple approaches, involving ectopic expression of key regulatory myogenic genes or small molecules cocktails, have been described by different groups to obtain SMPC towards cell-transplantation as a therapeutic approach to skeletal muscle diseases. However, hiPSCs-derived SMPC generated using transgene-free protocols are usually obtained in a low amount and resemble a more embryonal/fetal stage of differentiation.
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