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Query: "author" (Marco Vincenzo Narici) .

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Neuromuscular junction instability and altered intracellular calcium handling as early determinants of force loss during unloading in humans
Elena Monti, Carlo Reggiani, Martino V. Franchi, Luana Toniolo, Marco Sandri, Andrea Armani, Sandra Zampieri, Boštjan Šimunič, Rado Pišot, Marco Vincenzo Narici, 2021

Abstract: Unloading induces rapid skeletal muscle atrophy and functional decline. Importantly, force is lost at a much higher rate than muscle mass. We aimed to investigate the early determinants of the disproportionate loss of force compared to that of muscle mass in response to unloading. Ten young participants underwent 10 days of bed rest (BR). At baseline (BR0) and at 10 days (BR10), quadriceps femoris (QF) volume (VOL) and isometric maximum voluntary contraction (MVC) were assessed. At BR0 and BR10 blood samples and biopsies of vastus lateralis (VL) muscle were collected. Neuromuscular junction (NMJ) stability and myofibre innervation status were assessed, together with single fibre mechanical properties and sarcoplasmic reticulum (SR) calcium handling. From BR0 to BR10, QFVOL and MVC decreased by 5.2% (P = 0.003) and 14.3% (P < 0.001), respectively. Initial and partial denervation was detected from increased neural cell adhesion molecule (NCAM)-positive myofibres at BR10 compared with BR0 (+3.4%, P = 0.016). NMJ instability was further inferred from increased C-terminal agrin fragment concentration in serum (+19.2% at BR10, P = 0.031). Fast fibre cross-sectional area (CSA) showed a trend to decrease by 15% (P = 0.055) at BR10, while single fibre maximal tension (force/CSA) was unchanged. However, at BR10 SR Ca2+ release in response to caffeine decreased by 35.1% (P < 0.002) and 30.2% (P < 0.001) in fast and slow fibres, respectively, pointing to an impaired excitation%contraction coupling. These findings support the view that the early onset of NMJ instability and impairment in SR function are eligible mechanisms contributing to the greater decline in muscle force than in muscle size during unloading.
Keywords: Ca2+ dynamics, muscle atrophy, neuromuscular junction instability, sarcoplasmic reticulum, single fibre atrophy, single fibre contractile impairment, unloading
DiRROS - Published: 16.06.2021; Views: 466; Downloads: 450
.pdf Fulltext (3,39 MB)

The aging muscle in experimental bed rest : ǂa ǂsystematic review and meta-analysis
Filippo Giorgio Di Girolamo, Nicola Fiotti, Zoran Milanović, Roberta Situlin, Filippo Mearelli, Pierandrea Vinci, Boštjan Šimunič, Rado Pišot, Marco Vincenzo Narici, Gianni Biolo, 2021

Abstract: Background: Maintaining skeletal muscle mass and function in aging is crucial for preserving the quality of life and health. An experimental bed rest (BR) protocol is a suitable model to explore muscle decline on aging during inactivity. Objective: The purpose of this systematic review and meta-analysis was, therefore, to carry out an up-to-date evaluation of bed rest, with a specific focus on the magnitude of effects on muscle mass, strength, power, and functional capacity changes as well as the mechanisms, molecules, and pathways involved in muscle decay. Design: This was a systematic review and meta-analysis study. Data sources: We used PubMed, Medline; Web of Science, Google Scholar, and the Cochrane library, all of which were searched prior to April 23, 2020. A manual search was performed to cover bed rest experimental protocols using the following key terms, either singly or in combination: %Elderly Bed rest,% %Older Bed rest,% %Old Bed rest,% %Aging Bed rest,% %Aging Bed rest,% %Bed-rest,% and %Bedrest%. Eligibility criteria for selecting studies: The inclusion criteria were divided into four sections: type of study, participants, interventions, and outcome measures. The primary outcome measures were: body mass index, fat mass, fat-free mass, leg lean mass, cross-sectional area, knee extension power, cytokine pattern, IGF signaling biomarkers, FOXO signaling biomarkers, mitochondrial modulation biomarkers, and muscle protein kinetics biomarkers. Results: A total of 25 studies were included in the qualitative synthesis, while 17 of them were included in the meta-analysis. In total, 118 healthy elderly volunteers underwent 5-, 7-, 10-, or 14-days of BR and provided a brief sketch on the possible mechanisms involved. In the very early phase of BR, important changes occurred in the skeletal muscle, with significant loss of performance associated with a lesser grade reduction of the total body and muscle mass. Meta-analysis of the effect of bed rest on total body mass was determined to be small but statistically significant (ES = %0.45, 95% CI: %0.72 to %0.19, P < 0.001). Moderate, statistically significant effects were observed for total lean body mass (ES = %0.67, 95% CI: %0.95 to %0.40, P < 0.001) after bed rest intervention. Overall, total lean body mass was decreased by 1.5 kg, while there was no relationship between bed rest duration and outcomes (Z = 0.423, p = 672). The meta-analyzed effect showed that bed rest produced large, statistically significant, effects (ES = %1.06, 95% CI: %1.37 to %0.75, P < 0.001) in terms of the knee extension power. Knee extension power was decreased by 14.65 N/s. In contrast, to other measures, meta-regression showed a significant relationship between bed rest duration and knee extension power (Z = 4.219, p < 0.001). Moderate, statistically significant, effects were observed after bed rest intervention for leg muscle mass in both old (ES = %0.68, 95% CI: %0.96 to %0.40, P < 0.001) and young (ES = %0.51, 95% CI: %0.80 to %0.22, P < 0.001) adults. However, the magnitude of change was higher in older (MD = %0.86 kg) compared to younger (MD = %0.24 kg) adults. Conclusion: Experimental BR is a suitable model to explore the detrimental effects of inactivity in young adults, old adults, and hospitalized people. Changes in muscle mass and function are the two most investigated variables, and they allow for a consistent trend in the BR-induced changes. Mechanisms underlying the greater loss of muscle mass and function in aging, following inactivity, need to be thoroughly investigated.
Keywords: bed rest, aging, muscles, muscle physiopathology, muscle function
DiRROS - Published: 26.08.2021; Views: 401; Downloads: 245
.pdf Fulltext (1,32 MB)

Early biomarkers of altered renal function and orthostatic intolerance during 10-day bedrest
Grazia Tamma, Annarita Di Mise, Marianna Ranieri, Mariangela Centrone, Maria Venneri, Mariagrazia D'Agostino, Angela Ferrulli, Boštjan Šimunič, Marco Vincenzo Narici, Rado Pišot, Giovanna Valenti, 2022

Abstract: Exposure to actual or simulated microgravity results in alterations of renal function, fluid redistribution, and bone loss, which is coupled to a rise of urinary calcium excretion. We provided evidence that high calcium delivery to the collecting duct reduces local Aquaporin 2 (AQP2)-mediated water reabsorption under vasopressin action, thus limiting the maximal urinary concentration to reduce calcium saturation. To investigate early renal adaptation into simulated microgravity, we investigated the effects of 10 days of strict bedrest in 10 healthy volunteers. We report here that 10 days of inactivity are associated with a transient, significant decrease (day 5) in vasopressin (copeptin) paralleled by a decrease in AQP2 excretion, consistent with an increased central volume to the heart, resulting in reduced water reabsorption. Moreover, bedrest caused a significant increase in calciuria secondary to bone demineralization paralleled by a decrease in PTH. Urinary osteopontin, a glycoprotein exerting a protective effect on stone formation, was significantly reduced during bedrest. Moreover, a significant increase in adrenomedullin (day 5), a peptide with vasodepressor properties, was observed at day 5, which may contribute to the known reduced orthostatic capacity post-bedrest. We conclude that renal function is altered in simulated microgravity and is associated with an early increase in the risk of stone formation and reduced orthostatic capacity post-bedrest within a few days of inactivity.
Keywords: kidney, functions, bed rest, biomarkers, orthostatic intolerance, vasopressin, copeptin, aquaporin-2, adrenomedullin, calcium
DiRROS - Published: 20.04.2022; Views: 97; Downloads: 64
.pdf Fulltext (1,11 MB)

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