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Article ; Online: Increase of resting muscle stiffness, a less considered component of age-related skeletal muscle impairment

Lorenzo Marcucci / Carlo Reggiani

European Journal of Translational Myology (2020)

2020

Abstract: Elderly people perform more slowly movements of everyday life as rising from a chair, walking, and climbing stairs. This is in the first place due to the loss of muscle contractile force which is even more pronounced than the loss of muscle mass. In ... ...

Abstract	Elderly people perform more slowly movements of everyday life as rising from a chair, walking, and climbing stairs. This is in the first place due to the loss of muscle contractile force which is even more pronounced than the loss of muscle mass. In addition, a secondary, but not negligible, component is the rigidity or increased stiffness which requires greater effort to produce the same movement and limits the range of motion of the joints. In this short review, we discuss the possible determinants of the limitations of joint mobility in healthy elderly, starting with the age-dependent alterations of the articular structure and focusing on the increased stiffness of the skeletal muscles. Thereafter, the possible mechanisms of the increased stiffness of the muscle-tendon complex are considered, among them changes in the muscle fibers, alterations of the connective components (extracellular matrix or ECM, aponeurosis, fascia and tendon) and remodeling of the neural pattern of muscle activation with increased of antagonist co-activation.
Keywords	Joint mobility ; muscle stiffness ; aging ; connective tissue ; modeling ; Medicine ; R ; Human anatomy ; QM1-695
Subject code	796
Language	English
Publishing date	2020-06-01T00:00:00Z
Publisher	PAGEPress Publications
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Age Dependent Modification of the Metabolic Profile of the Tibialis Anterior Muscle Fibers in C57BL/6J Mice

Emiliana Giacomello / Emanuela Crea / Lucio Torelli / Alberta Bergamo / Carlo Reggiani / Gianni Sava / Luana Toniolo

International Journal of Molecular Sciences, Vol 21, Iss 3923, p

2020 Volume 3923

Abstract: Skeletal muscle aging is accompanied by mass reduction and functional decline, as a result of multiple factors, such as protein expression, morphology of organelles, metabolic equilibria, and neural communication. Skeletal muscles are formed by multiple ... ...

Abstract	Skeletal muscle aging is accompanied by mass reduction and functional decline, as a result of multiple factors, such as protein expression, morphology of organelles, metabolic equilibria, and neural communication. Skeletal muscles are formed by multiple fibers that express different Myosin Heavy Chains (MyHCs) and have different metabolic properties and different blood supply, with the purpose to adapt their contraction to the functional need. The fine interplay between the different fibers composing a muscle and its architectural organization determine its functional properties. Immunohistochemical and histochemical analyses of the skeletal muscle tissue, besides evidencing morphological characteristics, allow for the precise determination of protein expression and metabolic properties, providing essential information at the single-fiber level. Aiming to gain further knowledge on the influence of aging on skeletal muscles, we investigated the expression of the MyHCs, the Succinate Dehydrogenase (SDH) activity, and the presence of capillaries and Tubular Aggregates (TAs) in the tibialis anterior muscles of physiologically aging C57BL/6J mice aged 8 (adult), 18 (middle aged), and 24 months (old). We observed an increase of type-IIB fast-contracting fibers, an increase of the oxidative capacity of type-IIX and -IIA fibers, a general decrease of the capillarization, and the onset of TAs in type-IIB fibers. These data suggest that aging entails a selective modification of the muscle fiber profiles.
Keywords	skeletal muscle aging ; muscle fiber ; Myosin Heavy Chain ; metabolic profile ; capillaries ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2020-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Upregulation of Sarcolemmal Hemichannels and Inflammatory Transcripts with Neuromuscular Junction Instability during Lower Limb Unloading in Humans

Giuseppe Sirago / Julián Candia / Martino V. Franchi / Fabio Sarto / Elena Monti / Luana Toniolo / Carlo Reggiani / Emiliana Giacomello / Sandra Zampieri / Lisa M. Hartnell / Giuseppe De Vito / Marco Sandri / Luigi Ferrucci / Marco V. Narici

Biology, Vol 12, Iss 431, p

2023 Volume 431

Abstract: Human skeletal muscle atrophy and a disproportionate force loss occur within a few days of unloading in space and on Earth, but the underlying mechanisms are not fully understood. Disruption of neuromuscular junction homeostasis has been proposed as one ... ...

Abstract	Human skeletal muscle atrophy and a disproportionate force loss occur within a few days of unloading in space and on Earth, but the underlying mechanisms are not fully understood. Disruption of neuromuscular junction homeostasis has been proposed as one of the possible causes. Here, we investigated the potential mechanisms involved in this neuromuscular disruption induced by a 10-day unilateral lower limb suspension (ULLS) in humans. Specifically, we investigated hemichannels’ upregulation, neuromuscular junction and axonal damage, neurotrophins’ receptor downregulation and inflammatory transcriptional signatures. Biomarkers were evaluated at local and systemic levels. At the sarcolemmal level, changes were found to be associated with an increased expression of connexin 43 and pannexin-1. Upregulation of the inflammatory transcripts revealed by deep transcriptomics was found after 10 days of ULLS. The destabilisation of the neuromuscular junction was not accompanied by changes in the secretion of the brain-derived neurotrophic factor and neurotrophin-4, while their receptor, BDNF/NT growth factors receptor (TrkB), decreased. Furthermore, at 5 days of ULLS, there was already a significant upregulation of the serum neurofilament light chain concentration, an established clinical biomarker of axonal injury. At 10 days of ULLS, other biomarkers of early denervation processes appeared. Hence, short periods of muscle unloading induce sarcolemmal hemichannels upregulation, inflammatory transcripts upregulation, neuromuscular junction instability and axonal damage.
Keywords	disuse ; hemichannels ; inflammation ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2023-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Parvalbumin affects skeletal muscle trophism through modulation of mitochondrial calcium uptake

Gaia Butera / Denis Vecellio Reane / Marta Canato / Laura Pietrangelo / Simona Boncompagni / Feliciano Protasi / Rosario Rizzuto / Carlo Reggiani / Anna Raffaello

Cell Reports, Vol 35, Iss 5, Pp 109087- (2021)

2021

Abstract: Summary: Parvalbumin (PV) is a cytosolic Ca2+-binding protein highly expressed in fast skeletal muscle, contributing to an increased relaxation rate. Moreover, PV is an “atrogene” downregulated in most muscle atrophy conditions. Here, we exploit mice ... ...

Abstract	Summary: Parvalbumin (PV) is a cytosolic Ca2+-binding protein highly expressed in fast skeletal muscle, contributing to an increased relaxation rate. Moreover, PV is an “atrogene” downregulated in most muscle atrophy conditions. Here, we exploit mice lacking PV to explore the link between the two PV functions. Surprisingly, PV ablation partially counteracts muscle loss after denervation. Furthermore, acute PV downregulation is accompanied by hypertrophy and upregulation by atrophy. PV ablation has a minor impact on sarcoplasmic reticulum but is associated with increased mitochondrial Ca2+ uptake, mitochondrial size and number, and contacts with Ca2+ release sites. Mitochondrial calcium uniporter (MCU) silencing abolishes the hypertrophic effect of PV ablation, suggesting that mitochondrial Ca2+ uptake is required for hypertrophy. In turn, an increase of mitochondrial Ca2+ is required to enhance expression of the pro-hypertrophy gene PGC-1α4, whose silencing blocks hypertrophy due to PV ablation. These results reveal how PV links cytosolic Ca2+ control to mitochondrial adaptations, leading to muscle mass regulation.
Keywords	calcium buffer ; mitochondria ; skeletal muscle ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2021-05-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Fibre and extracellular matrix contributions to passive forces in human skeletal muscles

Lorenzo Marcucci / Michela Bondì / Giulia Randazzo / Carlo Reggiani / Arturo N Natali / Piero G Pavan

PLoS ONE, Vol 14, Iss 11, p e

An experimental based constitutive law for numerical modelling of the passive element in the classical Hill-type three element model.

2019 Volume 0224232

Abstract: The forces that allow body movement can be divided into active (generated by sarcomeric contractile proteins) and passive (sustained by intra-sarcomeric proteins, fibre cytoskeleton and extracellular matrix (ECM)). These are needed to transmit the active ...

Abstract	The forces that allow body movement can be divided into active (generated by sarcomeric contractile proteins) and passive (sustained by intra-sarcomeric proteins, fibre cytoskeleton and extracellular matrix (ECM)). These are needed to transmit the active forces to the tendon and the skeleton. However, the relative contribution of the intra- and extra- sarcomeric components in transmitting the passive forces is still under debate. There is limited data in the literature about human muscle and so it is difficult to make predictions using multiscale models, imposing a purely phenomenological description for passive forces. In this paper, we apply a method for the experimental characterization of the passive properties of fibres and ECM to human biopsy and propose their clear separation in a Finite Element Model. Experimental data were collected on human single muscle fibres and bundles, taken from vastus lateralis muscle of elderly subjects. Both were progressively elongated to obtain two stress-strain curves which were fitted to exponential equations. The mechanical properties of the extracellular passive components in a bundle of fibres were deduced by the subtraction of the passive tension observed in single fibres from the passive tension observed in the bundle itself. Our results showed that modulus and tensile load bearing capability of ECM are higher than those of fibres and defined their quantitative characterization that can be used in macroscopic models to study their role in the transmission of forces in physiological and pathophysiological conditions.
Keywords	Medicine ; R ; Science ; Q
Subject code	621
Language	English
Publishing date	2019-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Irisin Attenuates Muscle Impairment during Bed Rest through Muscle-Adipose Tissue Crosstalk

Andrea D’Amuri / Juana Maria Sanz / Stefano Lazzer / Rado Pišot / Bostjan Šimunič / Gianni Biolo / Giovanni Zuliani / Mladen Gasparini / Marco Narici / Bruno Grassi / Carlo Reggiani / Edoardo Dalla Nora / Angelina Passaro

Biology, Vol 11, Iss 7, p

2022 Volume 999

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 ... ...

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.
Keywords	inactivity ; FNDC5 gene expression ; myokines ; sarcopenia ; muscle fiber ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2022-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Alterations of Extracellular Matrix Mechanical Properties Contribute to Age-Related Functional Impairment of Human Skeletal Muscles

Piero Pavan / Elena Monti / Michela Bondí / Chenglei Fan / Carla Stecco / Marco Narici / Carlo Reggiani / Lorenzo Marcucci

International Journal of Molecular Sciences, Vol 21, Iss 3992, p

2020 Volume 3992

Abstract: Aging of human skeletal muscles is associated with increased passive stiffness, but it is still debated whether muscle fibers or extracellular matrix (ECM) are the determinants of such change. To answer this question, we compared the passive stress ... ...

Abstract	Aging of human skeletal muscles is associated with increased passive stiffness, but it is still debated whether muscle fibers or extracellular matrix (ECM) are the determinants of such change. To answer this question, we compared the passive stress generated by elongation of fibers alone and arranged in small bundles in young healthy (Y: 21 years) and elderly (E: 67 years) subjects. The physiological range of sarcomere length (SL) 2.5–3.3 μm was explored. The area of ECM between muscle fibers was determined on transversal sections with picrosirius red, a staining specific for collagen fibers. The passive tension of fiber bundles was significantly higher in E compared to Y at all SL. However, the resistance to elongation of fibers alone was not different between the two groups, while the ECM contribution was significantly increased in E compared to Y. The proportion of muscle area occupied by ECM increased from 3.3% in Y to 8.2% in E. When the contribution of ECM to bundle tension was normalized to the fraction of area occupied by ECM, the difference disappeared. We conclude that, in human skeletal muscles, the age-related reduced compliance is due to an increased stiffness of ECM, mainly caused by collagen accumulation.
Keywords	aging ; skeletal muscle ; resting tension ; extracellular matrix ; single muscle fiber ; collagen ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2020-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A 3D diffusional-compartmental model of the calcium dynamics in cytosol, sarcoplasmic reticulum and mitochondria of murine skeletal muscle fibers.

Lorenzo Marcucci / Marta Canato / Feliciano Protasi / Ger J M Stienen / Carlo Reggiani

PLoS ONE, Vol 13, Iss 7, p e

2018 Volume 0201050

Abstract: Variations of free calcium concentration ([Ca2+]) are powerful intracellular signals, controlling contraction as well as metabolism in muscle cells. To fully understand the role of calcium redistribution upon excitation and contraction in skeletal muscle ...

Abstract	Variations of free calcium concentration ([Ca2+]) are powerful intracellular signals, controlling contraction as well as metabolism in muscle cells. To fully understand the role of calcium redistribution upon excitation and contraction in skeletal muscle cells, the local [Ca2+] in different compartments needs to be taken into consideration. Fluorescent probes allow the determination of [Ca2+] in the cytosol where myofibrils are embedded, the lumen of the sarcoplasmic reticulum (SR) and the mitochondrial matrix. Previously, models have been developed describing intracellular calcium handling in skeletal and cardiac muscle cells. However, a comprehensive model describing the kinetics of the changes in free calcium concentration in these three compartments is lacking. We designed a new 3D compartmental model of the half sarcomere with radial symmetry, which accounts for diffusion of Ca2+ into the three compartments and simulates its dynamics at rest and at various rates of stimulation in mice skeletal muscle fibers. This model satisfactorily reproduces both the amplitude and time course of the variations of [Ca2+] in the three compartments in mouse fast fibers. As an illustration of the applicability of the model, we investigated the effects of Calsequestrin (CSQ) ablation. CSQ is the main Ca2+ buffer in the SR, localized in close proximity of its calcium release sites and near to the mitochondria. CSQ knock-out mice muscles still preserve a near-normal contractile behavior, but it is unclear whether this is caused by additional SR calcium buffering or a significant contribution of calcium entry from extracellular space, via stored-operated calcium entry (SOCE). The model enabled quantitative assessment of these two scenarios by comparison to measurements of local calcium in the cytosol, the SR and the mitochondria. In conclusion, the model represents a useful tool to investigate the impact of protein ablation and of pharmacological interventions on intracellular calcium dynamics in mice skeletal muscle.
Keywords	Medicine ; R ; Science ; Q
Subject code	572
Language	English
Publishing date	2018-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Physiological and Perceptual Responses to Nordic Walking in a Natural Mountain Environment

Alessandro Grainer / Livio Zerbini / Carlo Reggiani / Giuseppe Marcolin / James Steele / Gaspare Pavei / Antonio Paoli

International Journal of Environmental Research and Public Health, Vol 14, Iss 10, p

2017 Volume 1235

Abstract: Background: Interest around Nordic Walking (NW) has increased in recent years. However, direct comparisons of NW with normal walking (W), particularly in ecologically valid environments is lacking. The aim of our study was to compare NW and W, over long ... ...

Abstract	Background: Interest around Nordic Walking (NW) has increased in recent years. However, direct comparisons of NW with normal walking (W), particularly in ecologically valid environments is lacking. The aim of our study was to compare NW and W, over long distances in a natural mountain environment. Methods: Twenty one subjects (13 male/8 female, aged 41 ± 12 years, body mass index BMI 24.1 ± 3.7), walked three distinct uphill paths (length 2.2/3.4/7 km) with (NW) or without (W) walking poles over two separate days. Heart rate (HR), energy expenditure (EE), step length (SL), walking speed (WS), total steps number (SN) and rating of perceived exertion (RPE) were monitored. Results: HR (+18%) and EE (+20%) were higher in NW than in W whilst RPE was similar. SN (−12%) was lower and SL (+15%) longer in NW. WS was higher (1.64 vs. 1.53 m s−1) in NW. Conclusions: Our data confirm that, similarly to previous laboratory studies, differences in a range of walking variables are present between NW and W when performed in a natural environment. NW appears to increase EE compared to W, despite a similar RPE. Thus, NW could be a useful as aerobic training modality for weight control and cardiorespiratory fitness.
Keywords	pole walking locomotion ; energy expenditure ; RPE ; natural environment ; trekking ; Medicine ; R
Subject code	629
Language	English
Publishing date	2017-10-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Impaired Intracellular Ca 2+ Dynamics, M-Band and Sarcomere Fragility in Skeletal Muscles of Obscurin KO Mice

Enrico Pierantozzi / Péter Szentesi / Cecilia Paolini / Beatrix Dienes / János Fodor / Tamás Oláh / Barbara Colombini / Dilson E. Rassier / Egidio Maria Rubino / Stephan Lange / Daniela Rossi / László Csernoch / Maria Angela Bagni / Carlo Reggiani / Vincenzo Sorrentino

International Journal of Molecular Sciences, Vol 23, Iss 1319, p

2022 Volume 1319

Abstract: Obscurin is a giant sarcomeric protein expressed in striated muscles known to establish several interactions with other proteins of the sarcomere, but also with proteins of the sarcoplasmic reticulum and costameres. Here, we report experiments aiming to ... ...

Abstract	Obscurin is a giant sarcomeric protein expressed in striated muscles known to establish several interactions with other proteins of the sarcomere, but also with proteins of the sarcoplasmic reticulum and costameres. Here, we report experiments aiming to better understand the contribution of obscurin to skeletal muscle fibers, starting with a detailed characterization of the diaphragm muscle function, which we previously reported to be the most affected muscle in obscurin ( Obscn ) KO mice. Twitch and tetanus tension were not significantly different in the diaphragm of WT and Obscn KO mice, while the time to peak (TTP) and half relaxation time (HRT) were prolonged. Differences in force-frequency and force-velocity relationships and an enhanced fatigability are observed in an Obscn KO diaphragm with respect to WT controls. Voltage clamp experiments show that a sarcoplasmic reticulum’s Ca 2+ release and SERCA reuptake rates were decreased in muscle fibers from Obscn KO mice, suggesting that an impairment in intracellular Ca 2+ dynamics could explain the observed differences in the TTP and HRT in the diaphragm. In partial contrast with previous observations, Obscn KO mice show a normal exercise tolerance, but fiber damage, the altered sarcomere ultrastructure and M-band disarray are still observed after intense exercise.
Keywords	obscurin ; skeletal muscle ; calcium dynamics ; muscle fiber damage ; kinetics of contraction ; sarcoplasmic reticulum ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	333
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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