1. Spaceflight on the ISS changed the skeletal muscle proteome of two astronautsMarta Murgia, Joern Rittweger, Carlo Reggiani, Roberto Bottinelli, Matthias Mann, Stefano Schiaffino, Marco Vicenzo 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: 144; Prenosov: 81
 Celotno besedilo (1,55 MB)
Gradivo ima več datotek! Več... |
2. Effects of a 2-year exercise training on neuromuscular system health in older individuals with low muscle functionElena Monti, Sara Tagliaferri, Sandra Zampieri, Fabio Sarto, Giuseppe Sirago, Martino V. Franchi, Andrea Ticinesi, Yari Longobucco, Elisa Adorni, Marco Vicenzo Narici, 2023, izvirni znanstveni članek Ključne besede: skeletal muscles, C-terminal agrin fragment, neurofilament light chain, exercise interventions, sarcopenia, elderly
Objavljeno v DiRROS: 15.12.2023; Ogledov: 723; Prenosov: 260
Celotno besedilo (487,80 KB)
Gradivo ima več datotek! Več... |
3. Upregulation of sarcolemmal hemichannels and inflammatory transcripts with neuromuscular junction instability during lower limb unloading in humansGiuseppe Sirago, Julián Candia, Martino V. Franchi, Fabio Sarto, Elena Monti, Luana Toniolo, Carlo Reggiani, Emiliana Giacomello, Sandra Zampieri, Marco Vicenzo Narici, 2023, izvirni znanstveni članek Ključne besede: skeletal muscles, neuromuscular junction, sarcolemmal hemichannels, lower limb
Objavljeno v DiRROS: 14.12.2023; Ogledov: 688; Prenosov: 288
Celotno besedilo (4,79 MB)
Gradivo ima več datotek! Več... |
4. Retinal venular vessel diameters are smaller during ten days of bed restAdam Salon, Göktuğ Mert Çiftci, Damir Zubac, Boštjan Šimunič, Rado Pišot, Marco Vicenzo Narici, Per Morten Fredriksen, Benedicta Ngwenchi Nkeh-Chungag, Harald Sourij, Nandu Goswami, 2023, izvirni znanstveni članek Povzetek: Older individuals experience cardiovascular dysfunction during extended bedridden hospital or care home stays. Bed rest is also used as a model to simulate accelerated vascular deconditioning occurring during spacefight. This study investigates changes in retinal microcirculation during a tenday bed rest protocol. Ten healthy young males (22.9± 4.7 years; body mass index: 23.6± 2.5 kg·m–2) participated in a strictly controlled repeated-measures bed rest study lasting ten days. High-resolution images were obtained using a hand-held fundus camera at baseline, daily during the 10 days of bed rest, and 1 day after re-ambulation. Retinal vessel analysis was performed using a semi-automated software system to obtain metrics for retinal arteriolar and venular diameters, central retinal artery equivalent and central retinal vein equivalent, respectively. Data analysis employed a mixed linear model. At the end of the bed rest period, a signifcant decrease in retinal venular diameter was observed, indicated by a signifcantly lower central retinal vein equivalent (from 226.1 µm, CI 8.90, to 211.4 µm, CI 8.28, p= .026), while no signifcant changes in central retinal artery equivalent were noted. Prolonged bed rest confnement resulted in a signifcant (up to 6.5%) reduction in retinal venular diameter. These fndings suggest that the changes in retinal venular diameter during bedrest may be attributed to plasma volume losses and refect overall (cardio)-vascular deconditioning.
Ključne besede: eyes, retinal venular vessel, venske žile, bed rest, gibalna neaktivnost
Objavljeno v DiRROS: 23.11.2023; Ogledov: 1117; Prenosov: 370
Celotno besedilo (1,07 MB)
Gradivo ima več datotek! Več... |
5. Pathophysiological mechanisms of reduced physical activity : insights from the human step reduction model and animal analoguesFabio Sarto, Roberto Bottinelli, Martino V. Franchi, Simone Porcelli, Boštjan Šimunič, Rado Pišot, Marco Vicenzo Narici, 2023, pregledni znanstveni članek Povzetek: Physical inactivity represents a heavy burden for modern societies and is spreading worldwide, it is a recognised pandemic and is the fourth cause of global mortality. Not surprisingly, there is an increasing interest in longitudinal studies on the impact of reduced physical activity on different physiological systems. This narrative review focuses on the pathophysiological mechanisms of step reduction (SR), an experimental paradigm that involves a sudden decrease in participants’ habitual daily steps to a lower level, mimicking the effects of a sedentary lifestyle. Analogous animal models of reduced physical activity, namely the “wheel-lock” and the “cage reduction” models, which can provide the foundation for human studies, are also discussed. The empirical evidence obtained thus far shows that even brief periods of reduced physical activity can lead to substantial alterations in skeletal muscle health and metabolic function. In particular, decrements in lean/muscle mass, muscle function, muscle protein synthesis, cardiorespiratory fitness, endothelial function and insulin sensitivity, together with an increased fat mass and inflammation, have been observed. Exercise interventions seem particularly effective for counteracting these pathophysiological alterations induced by periods of reduced physical activity. A direct comparison of SR with other human models of unloading, such as bed rest and lower limb suspension/immobilisation, is presented. In addition, we propose a conceptual framework aiming to unravel the mechanisms of muscle atrophy and insulin resistance in the specific context of reduced ambulatory activity. Finally, methodological considerations, knowledge gaps and future directions for both animal and human models are also discussed in the review.
Ključne besede: physical inactivity, cage reduction, insulin sensitivity, muscle atrophy
Objavljeno v DiRROS: 29.06.2023; Ogledov: 758; Prenosov: 468
Celotno besedilo (6,91 MB)
Gradivo ima več datotek! Več... |
6. Sarcopenia parameters in active older adults – an eight-year longitudinal studyKaja Teraž, Uroš Marušič, Miloš Kalc, Boštjan Šimunič, Primož Pori, Bruno Grassi, Stefano Lazzer, Marco Vicenzo Narici, Mojca Gabrijelčič Blenkuš, Pietro Enrico Di Prampero, Carlo Reggiani, Angelina Passaro, Gianni Biolo, Mladen Gasparini, Rado Pišot, 2023, izvirni znanstveni članek Povzetek: Background Sarcopenia is a common skeletal muscle syndrome that is common in older adults but can be mitigated by adequate and regular physical activity. The development and severity of sarcopenia is favored by several factors, the most influential of which are a sedentary lifestyle and physical inactivity. The aim of this observational longitudinal cohort study was to evaluate changes in sarcopenia parameters, based on the EWGSOP2 definition in a population of active older adults after eight years. It was hypothesized that selected active older adults would perform better on sarcopenia tests than the average population. Methods The 52 active older adults (22 men and 30 women, mean age: 68.4±5.6 years at the time of their first evaluation) participated in the study at two time points eight-years apart. Three sarcopenia parameters were assessed at both time points: Muscle strength (handgrip test), skeletal muscle mass index, and physical performance (gait speed), these parameters were used to diagnose sarcop0enia according to the EWGSOP2 definition. Additional motor tests were also performed at follow-up measurements to assess participants’ overall fitness. Participants self-reported physical activity and sedentary behavior using General Physical Activity Questionnaire at baseline and at follow-up measurements. Results In the first measurements we did not detect signs of sarcopenia in any individual, but after 8 years, we detected signs of sarcopenia in 7 participants. After eight years, we detected decline in ; muscle strength (-10.2%; p<.001), muscle mass index (-5.4%; p<.001), and physical performance measured with gait speed (-28.6%; p<.001). Similarly, self-reported physical activity and sedentary behavior declined, too (-25.0%; p=.030 and −48.5%; p<.001, respectively). Conclusions Despite expected lower scores on tests of sarcopenia parameters due to age-related decline, participants performed better on motor tests than reported in similar studies. Nevertheless, the prevalence of sarcopenia was consistent with most of the published literature. Trial registration The clinical trial protocol was registered on ClinicalTrials.gov, identifier: NCT04899531
Ključne besede: elderly, physical activities, sedentary behavior, skeletal muscle disorder, sarcopenia
Objavljeno v DiRROS: 29.05.2023; Ogledov: 672; Prenosov: 359
Celotno besedilo (1,47 MB)
Gradivo ima več datotek! Več... |
7. Impact of 10-day bed rest on serum levels of irisin and markers of musculoskeletal metabolismAngela Oranger, Giuseppina Storlino, Manuela Dicarlo, Roberta Zerlotin, Patrizia Pignataro, Lorenzo Sanesi, Marco Vicenzo Narici, Rado Pišot, Boštjan Šimunič, Graziana Colaianni, 2023, izvirni znanstveni članek Povzetek: The bed rest (BR) is a ground-based model to simulate microgravity mimicking skeletal-muscle alterations as in spaceflight. Molecular coupling between bone and muscle might be involved in physiological and pathological conditions. Thus, the new myokine irisin and bone-muscle turnover markers have been studied during and after 10 days of BR. Ten young male individuals were subjected to 10 days of horizontal BR. Serum concentrations of irisin, myostatin, sclerostin, and haptoglobin were assessed, and muscle tissue gene expression on vastus lateralis biopsies was determined. During 10-days BR, we observed no significant fluctuation levels of irisin, myostatin, and sclerostin. Two days after BR (R+2), irisin serum levels significantly decreased while myostatin, sclerostin, and haptoglobin were significantly increased compared with BR0. Gene expression of myokines, inflammatory molecules, transcription factors, and markers of muscle atrophy and senescence on muscle biopsies were not altered, suggesting that muscle metabolism of young, healthy subjects is able to adapt to the hypomobility condition during 10-day BR. However, when subjects were divided according to irisin serum levels at BR9, muscle ring finger-1 mRNA expression was significantly lower in subjects with higher irisin serum levels, suggesting that this myokine may prevent the triggering of muscle atrophy. Moreover, the negative correlation between p21 mRNA and irisin at BR9 indicated a possible inhibitory effect of the myokine on the senescence marker. In conclusion, irisin could be a prognostic marker of hypomobility-induced muscle atrophy, and its serum levels could protect against muscle deterioration by preventing and/or delaying the expression of atrophy and senescence cellular markers.
Objavljeno v DiRROS: 13.12.2022; Ogledov: 1054; Prenosov: 600
Celotno besedilo (827,16 KB)
Gradivo ima več datotek! Več... |
8. Irisin attenuates muscle impairment during bed rest through muscle-adipose tissue crosstalkAndrea D'Amuri, Juana Maria Sanz, Stefano Lazzer, Rado Pišot, Boštjan Šimunič, Gianni Biolo, Giovanni Zuliani, Mladen Gasparini, Marco Vicenzo Narici, Bruno Grassi, Carlo Reggiani, Edoardo Dalla Nora, Angelina Passaro, 2022, izvirni znanstveni članek Povzetek: Simple Summary: Irisin is a known myokine secreted mainly by the muscle that is produced after physical activity. It induces browning in the adipose tissue with a consequent increase in mitochondrial oxidation of lipids and reduction of insulin resistance; thus, it has been hypothesized that irisin was the molecule mediating most of the beneficial effects related to exercise on adipose tissue and consequently on the whole organism. In our study we observed that extreme physical inactivity induces the loss of muscle mass and function, and an increase in the body adipose tissue as expected. However, of note, circulating irisin levels were increased secondary to enhanced irisin synthesis mainly from adipose tissue rather than muscle. In addition, subjects who produced more irisin had reduced muscle impairment. Therefore, our hypothesis is that there is negative feedback within the muscle-adipose tissue crosstalk, specifically not only does the muscle influence the adipose tissue through irisin during exercise, but also the adipose tissue protects the muscle during inactivity.Abstract: The detrimental effect of physical inactivity on muscle characteristics are well known. Irisin, an exercise-induced myokine cleaved from membrane protein fibronectin type III domain-containing protein-5 (FNDC5), mediates at least partially the metabolic benefits of exercise. This study aimed to assess the interplay between prolonged inactivity, circulating irisin, muscle performance, muscle fibers characteristics, as well as the FNDC5 gene expression (FNDC5ge) in muscle and adipose tissue among healthy subjects. Twenty-three healthy volunteers were tested before and after 14 days of Bed Rest, (BR). Post-BR circulating levels of irisin significantly increased, whereas body composition, muscle performance, and muscle fiber characteristics deteriorated. Among the subjects achieving the highest post-BR increase of irisin, the lowest reduction in maximal voluntary contraction and specific force of Fiber Slow/1, the highest increase of FNDC5ge in adipose tissue, and no variation of FNDC5ge in skeletal muscle were recorded. Subjects who had the highest FNDC5ge in adipose tissue but not in muscle tissue showed the highest circulating irisin levels and could better withstand the harmful effect of BR.
Ključne besede: physical inactivity, bed rest, FNDC5 gene expression, myokines, sarcopenia, muscles fiber
Objavljeno v DiRROS: 07.07.2022; Ogledov: 1192; Prenosov: 643
Celotno besedilo (798,63 KB)
Gradivo ima več datotek! Več... |
9. Early biomarkers of altered renal function and orthostatic intolerance during 10-day bedrestGrazia Tamma, Annarita Di Mise, Marianna Ranieri, Mariangela Centrone, Maria Venneri, Mariagrazia D'Agostino, Angela Ferrulli, Boštjan Šimunič, Marco Vicenzo Narici, Rado Pišot, Giovanna Valenti, 2022, izvirni znanstveni članek Povzetek: 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.
Ključne besede: kidney, functions, bed rest, biomarkers, orthostatic intolerance, vasopressin, copeptin, aquaporin-2, adrenomedullin, calcium
Objavljeno v DiRROS: 20.04.2022; Ogledov: 1170; Prenosov: 729
Celotno besedilo (1,11 MB)
Gradivo ima več datotek! Več... |
10. The aging muscle in experimental bed rest : ǂa ǂsystematic review and meta-analysisFilippo Giorgio Di Girolamo, Nicola Fiotti, Zoran Milanović, Roberta Situlin, Filippo Mearelli, Pierandrea Vinci, Boštjan Šimunič, Rado Pišot, Marco Vicenzo Narici, Gianni Biolo, 2021, pregledni znanstveni članek Povzetek: 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.
Ključne besede: bed rest, aging, muscles, muscle physiopathology, muscle function
Objavljeno v DiRROS: 26.08.2021; Ogledov: 2025; Prenosov: 1262
Celotno besedilo (1,32 MB)
Gradivo ima več datotek! Več... |
