11. 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: 561; Prenosov: 364
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12. The use of tensiomyography in older adults : a systematic reviewKatarina Puš, Armin Paravlić, Boštjan Šimunič, 2023, pregledni znanstveni članek Povzetek: Introduction: Aging of skeletal muscles results in a cascade of events negatively affecting muscle mass, strength, and function, leading to reduced mobility, increased risk of falls, disability, and loss of independence. To date, different methods are used to assess muscle mechanical function, tensiomyography (TMG) being one of them. The aim of this review was twofold: to summarize the evidence-based usefulness of tensiomyography in older adults and to establish reference values for the main tensiomyography parameters in older adults. Methods: The PubMed, Web of Science, SPORTDiscus, and tensiomyography databases were searched from inception until 25 December 2022. Studies investigating older adults (aged 60+ years) that reported tensiomyographyderived parameters such as contraction time (Tc) and/or maximal displacement (Dm) were included. Methodological quality was assessed using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Results: In total, eight studies satisfied the inclusion criteria. Tensiomyography has been used on different groups of older adults, including asymptomatic, master athletes, patients with peripheral arterial disease, and patients with end-stage knee osteoarthritis with a mean age of 71.5 ± 5.38 (55.7% male subjects). The most evaluated were leg muscles such as vastus lateralis (VL), gastrocnemius medialis (GM), and biceps femoris (BF). The present review demonstrates that tensiomyography is used to assess neuromuscular function in asymptomatic and diseased older adults. When compared to asymptomatic individuals, power master athletes, knee osteoarthritis patients, and patients diagnosed with peripheral arterial disease have the shortest Tc in BF, VL, and GM muscles, respectively. On the other hand, endurance master athletes showed the longest Tc in all three evaluated muscles. Less mobile, nursing-home residents showed higher Dm in VL and BF, while lower Dm in GM than the asymptomatic group. The knee osteoarthritis group showed the largest Dm in BF and VL while having the smallest Dm in GM. Conclusion: Tensiomyography can serve as a valuable tool for assessing neuromuscular function in older adults. The method is sensitive to muscle composition, architecture, and (pre) atrophic changes of the skeletal muscles and might be responsive to muscle quality changes in aging and diseased populations. Ključne besede: sport, muscle function, elderly, neuromuscular function, normative values, TMG Objavljeno v DiRROS: 27.06.2023; Ogledov: 491; Prenosov: 297
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13. 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: 507; Prenosov: 265
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15. Inter-person differences in isometric coactivations of triceps surae and tibialis anterior decrease in young, but not in older adults after 14 days of bed restMatjaž Divjak, Gašper Sedej, Nina Murks, Mitja Gerževič, Uroš Marušič, Rado Pišot, Boštjan Šimunič, Aleš Holobar, 2022, izvirni znanstveni članek Povzetek: We examined activation patterns of the gastrocnemius medialis (GM), gastrocnemius lateralis (GL), soleus (SO), and tibialis anterior (TA) muscles in eight older (58.4 ± 3.3 years) and seven young (23.1 ± 2.9 years) participants, before and after 14 days of horizontal bed rest. Visual feedback on the exerted muscle torque was provided to the participants. The discharge patterns of individual motor units (MUs) were studied in three repetitions of isometric plantar flexion at 30 and 60% of Maximum Voluntary Contraction (MVC), before, and 1 day after the 14-day bed rest, respectively. In the GL and GM muscles, the older participants demonstrated higher MU discharge rates than the young, regardless of the contraction level, both before and after the bed rest. In the TA and SO muscles, the differences between the older and young participants were less consistent. Detailed analysis revealed person-specific changes in the MU discharge rates after the bed rest. To quantify the coactivation patterns we calculated the correlation coefficients between the cumulative spike trains of identified MUs from each muscle, and measured the root mean square difference of the correlation coefficients between the trials of the same session (intra-session variability) and between different sessions (inter-session variability) in each participant (intra-person comparison) and across participants (inter-person comparison). In the intra-person comparison, the inter-session variability was higher than the intra-session variability, either before or after the bed rest. At 60% MVC torque, the young demonstrated higher inter-person variability of coactivation than the older participants, but this variability decreased significantly after the bed rest. In older participants, inter-person variability was consistently lower at 60% than at 30% MVC torque. In young participants, inter-person variability became lower at 60% than at 30% MVC torque only after the bed rest. Precaution is required when analyzing the MU discharge and coactivation patterns, as individual persons demonstrate individual adaptations to aging or bed rest. Ključne besede: high density electromyography, muscle disuse, motor units, discharge rate, aging Objavljeno v DiRROS: 05.09.2022; Ogledov: 864; Prenosov: 463
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16. 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: 1850; Prenosov: 1081
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17. Neuromuscular junction instability and altered intracellular calcium handling as early determinants of force loss during unloading in humansElena Monti, Carlo Reggiani, Martino V. Franchi, Luana Toniolo, Marco Sandri, Andrea Armani, Sandra Zampieri, Boštjan Šimunič, Rado Pišot, Marco Vicenzo Narici, 2021, izvirni znanstveni članek Povzetek: 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. Ključne besede: Ca2+ dynamics, muscle atrophy, neuromuscular junction instability, sarcoplasmic reticulum, single fibre atrophy, single fibre contractile impairment, unloading Objavljeno v DiRROS: 16.06.2021; Ogledov: 1360; Prenosov: 1226
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