1. Neuromuscular junction instability with inactivity : morphological and functional changes after 10 days of bed rest in older adultsStefano Schiaffino, Evgeniia Motanova, Fabio Sarto, Samuele Negro, Marco Pirazzini, Ornella Rossetto, Michela Rigoni, Daniel W Stashuk, Mladen Gasparini, Boštjan Šimunič, Rado Pišot, Marco Vincenzo Narici, 2025, izvirni znanstveni članek Povzetek: The neuromuscular junction (NMJ) plays a key role in modulating muscle contraction,but the impact of short-term disuse on NMJ structure and function, particularly in older humans,remains unclear. This study aimed to investigate NMJ alterations following 10 days of horizontalbed rest in 10 older males (68.5 ± 2.6 years). Before and after bed rest, vastus lateralis musclebiopsies were obtained to evaluate NMJ morphology, intramuscular EMG (iEMG) was recordedto assess NMJ function and blood samples were collected to determine circulating C-terminal agrinfragment (CAF) concentration, a biomarker of NMJ remodelling. In a sub-cohort of six participantswho had NMJs in both pre- and post-bed rest biopsies, we observed altered NMJ morphology,including reduced overlap between NMJ terminals, as well as increased endplate area and peri-meter. CAF concentration was elevated after bed rest, suggesting ongoing NMJ remodelling. iEMGanalysis showed increased motor unit potential complexity and reduced firing rate. In addition,we observed impaired NMJ transmission, inferred from increased near-fibre jiggle and segmentjitter. These findings suggest that older male individuals are susceptible to NMJ remodelling andimpaired transmission with short-term disuse, providing valuable insights into the morphologicaland functional consequences of inactivity in an ageing population. Our study highlights theimportance of developing interventions for mitigating the detrimental consequences of inactivityon neuromuscular health in older adults, which they frequently experience following injury, trauma,illness or surgery.
Ključne besede: ageing, C-terminal agrin, fragment disuse, electromyography, motor unit, NMJ unloading
Objavljeno v DiRROS: 19.03.2025; Ogledov: 130; Prenosov: 159
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2. Spaceflight on the ISS changed the skeletal muscle proteome of two astronautsMarta Murgia, Joern Rittweger, Carlo Reggiani, Roberto Bottinelli, Matthias Mann, Stefano Schiaffino, Marco Vincenzo Narici, 2024, izvirni znanstveni članek Povzetek: Skeletal muscle undergoes atrophy and loss of force during long space missions, when astronauts are persistently exposed to altered gravity and increased ionizing radiation. We previously carried out mass spectrometry-based proteomics from skeletal muscle biopsies of two astronauts, taken before and after a mission on the International Space Station. The experiments were part of an effort to find similarities between spaceflight and bed rest, a ground-based model of unloading, focused on proteins located at the costameres. We here extend the data analysis of the astronaut dataset and show compartment-resolved changes in the mitochondrial proteome, remodeling of the extracellular matrix and of the antioxidant response. The astronauts differed in their level of onboard physical exercise, which correlated with their respective preservation of muscle mass and force at landing in previous analyses. We show that the mitochondrial proteome downregulation during spaceflight, particularly the inner membrane and matrix, was dramatic for both astronauts. The expression of autophagy regulators and reactive oxygen species scavengers, however, showed partially opposite expression trends in the two subjects, possibly correlating with their level of onboard exercise. As mitochondria are primarily affected in many different tissues during spaceflight, we hypothesize that reactive oxygen species (ROS) rather than mechanical unloading per se could be the primary cause of skeletal muscle mitochondrial damage in space. Onboard physical exercise might have a strong direct effect on the prevention of muscle atrophy through mechanotransduction and a subsidiary effect on mitochondrial quality control, possibly through upregulation of autophagy and anti-oxidant responses.
Ključne besede: skeletal muscles, microgravity, muscle atrophy, autophagy
Objavljeno v DiRROS: 12.11.2024; Ogledov: 340; Prenosov: 382
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