Showing papers by "Marco Narici published in 2020"

Alterations of Extracellular Matrix Mechanical Properties Contribute to Age-Related Functional Impairment of Human Skeletal Muscles.

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.

The Time-Course of Changes in Muscle Mass, Architecture and Power During 6 Weeks of Plyometric Training.

Abstract: Purpose To investigate the time-course of changes in knee-extensors muscle mass, architecture and function in response to plyometric training (PLT) performed on a novel training device, the Tramp-Trainer. This machine consists in a trampoline connected to an inclined sledge which allows the performance of repeated jumps while the subject is sitting on a chair. Methods Eight healthy males (173.6 ± 4.7 cm, 69.7 ± 13.5 kg, 25.3 ± 4.6 years) underwent 6 weeks of bilateral PLT on the tramp-trainer machine. Training was performed three times per week (between 120 and 150 bounces per session). Knee-extensor maximum voluntary torque (MVT) and power, quadriceps femoris (QF) volume (VOL), cross-sectional area from the 20% to the 60% of femur length and CSA mean , together with vastus lateralis (VL) architecture (fascicle length, Lf, and pennation angle, PA) were assessed after 2, 4, and 6 weeks of PLT. Results All results are presented as changes versus baseline values. MVT increased by 17.8% (week 2, p < 0.001) and 22.2% (week 4, p < 0.01), respectively, and declined to 13.3% (p < 0.05) at week 6 of PLT. Power increased by 18.2% (week 4, p < 0.05) and 19.7% (week 6, p < 0.05). QF VOL increased by 4.7% (week 4, p < 0.05) and 5.8% (week 6, p < 0.01); VL VOL increased by 5.2%, (p < 0.05), 8.2%, (p < 0.01), and 9.6% (p < 0.05) at weeks 2, 4, and 6, respectively. An increase in Lf was detected already at wk 2 (2.2%, p < 0.05), with further increase at 4 and 6 weeks of PLT (4 and 4.4%, respectively, p < 0.01). PA increased by 5.8% (p < 0.05) at week 6. Significant positive correlations were found between CSA mean and Power (R2 = 0.46, p < 0.001) and between QF VOL and Power (R2 = 0.44, p < 0.024). Conclusions PLT induced rapid increases in muscle volume, fascicle length, pennation angle, torque and power in healthy younger adults. Notably, changes in VL VOL and Lf were detectable already after 2 weeks, followed by increases in knee extensors VOL and power from week 4 of PLT. Since the increase in CSA mean and QF VOL cannot fully explain the increment in muscle power, it is likely that other factors (such as adaptations in neural drive or tendon mechanical properties) may have contributed to such fucntional changes.

Muscle Hypertrophy and Architectural Changes in Response to Eight-Week Neuromuscular Electrical Stimulation Training in Healthy Older People.

Abstract: Loss of muscle mass of the lower limbs and of the spine extensors markedly impairs locomotor ability and spine stability in old age. In this study, we investigated whether 8 w of neuromuscular electrical stimulation (NMES) improves size and architecture of the lumbar multifidus (LM) and vastus lateralis (VL) along with locomotor ability in healthy older individuals. Eight volunteers (aged 65 ≥ years) performed NMES 3 times/week. Eight sex- and age-matched individuals served as controls. Functional tests (Timed Up and Go test (TUG) and Five Times Sit-to-Stand Test (FTSST)), VL muscle architecture (muscle thickness (MT), pennation angle (PA), and fiber length (FL)), along with VL cross-sectional area (CSA) and both sides of LM were measured before and after by ultrasound. By the end of the training period, MT and CSA of VL increased by 8.6% and 11.4%, respectively. No significant increases were observed in FL and PA. LM CSA increased by 5.6% (left) and 7.1% (right). Interestingly, all VL architectural parameters significantly decreased in the control group. The combined NMES had a large significant effect on TUG (r = 0.50, p = 0.046). These results extend previous findings on the hypertrophic effects of NMES training, suggesting to be a useful mean for combating age-related sarcopenia.

Role of the Extracellular Matrix in Loss of Muscle Force With Age and Unloading Using Magnetic Resonance Imaging, Biochemical Analysis, and Computational Models.

Abstract: The focus of this review is the application of advanced MRI to study the effect of aging and disuse related remodeling of the extracellular matrix (ECM) on force transmission in the human musculoskeletal system Structural MRI includes (i) ultra-low echo times (UTE) maps to visualize and quantify the connective tissue, (ii) diffusion tensor imaging (DTI) modeling to estimate changes in muscle and ECM microstructure, and (iii) magnetization transfer contrast imaging to quantify the macromolecular fraction in muscle Functional MRI includes dynamic acquisitions during contraction cycles enabling computation of the strain tensor to monitor muscle deformation Further, shear strain extracted from the strain tensor may be a potential surrogate marker of lateral transmission of force Biochemical and histological analysis of muscle biopsy samples can provide "gold-standard" validation of some of the MR findings The review summarizes biochemical studies of ECM adaptations with age and with disuse A brief summary of animal models is included as they provide experimental confirmation of longitudinal and lateral force transmission pathways Computational muscle models enable exploration of force generation and force pathways and elucidate the link between structural adaptations and functional consequences MR image findings integrated in a computational model can explain and predict subject specific functional changes to structural adaptations Future work includes development and validation of MRI biomarkers using biochemical analysis of muscle tissue as a reference standard and potential translation of the imaging markers to the clinic to noninvasively monitor musculoskeletal disease conditions and changes consequent to rehabilitative interventions

Remodeling the Skeletal Muscle Extracellular Matrix in Older Age-Effects of Acute Exercise Stimuli on Gene Expression.

Abstract: With advancing age, the skeletal muscle extracellular matrix (ECM) undergoes fibrotic changes that may lead to increased muscle stiffness, injury susceptibility and strength loss. This study tested the potential of different exercises to counter these changes by stimulating the activity of genes associated with ECM remodeling. Twenty-six healthy men (66.9 ± 3.9 years) were stratified to two of four groups, performing unilateral (i) conventional resistance exercise, (ii) conventional resistance exercise followed by self-myofascial release (CEBR), (iii) eccentric-only exercise (ECC) or (iv) plyometric jumps (PLY). The non-trained leg served as control. Six hours post-exercise, vastus lateralis muscle biopsy samples were analyzed for the expression of genes associated with ECM collagen synthesis (COL1A1), matrix metallopeptidases (collagen degradation; MMPs) and peptidase inhibitors (TIMP1). Significant between-group differences were found for MMP3, MMP15 and TIMP1, with the greatest responses in MMP3 and TIMP1 seen in CEBR and in MMP15 in ECC. MMP9 (3.24-3.81-fold change) and COL1A1 (1.47-2.40-fold change) were increased in CEBR and PLY, although between-group differences were non-significant. The expression of ECM-related genes is exercise-specific, with CEBR and PLY triggering either earlier or stronger remodeling than other stimuli. Training studies will test whether execution of such exercises may help counter age-associated muscle fibrosis.

Longitudinal hypertrophic and transcriptional responses to high-load eccentric-concentric vs concentric training in males

Abstract: High-load eccentric training reputedly produces greater muscle hypertrophy than concentric training, possibly due to greater loading and/or inflammation. We quantified the temporal impact of combined maximal concentric-eccentric training vs maximal concentric training on muscle cross-sectional area (CSA), volume, and targeted mRNA expression (93 transcripts). Eight recreationally active males (24 ± 5 years, BMI 23.5 ± 2.5 kg/m2 ) performed 3 x 30 maximal eccentric isokinetic knee extensions and 2 x 30 maximal concentric knee extensions in dominant limb (ECC + CON) and 5 x 30 maximal concentric contractions (CON) in the non-dominant limb for 12 weeks (all 90°/s, 3x/wk). Quadriceps muscle CSA and volume were measured at baseline, 28 days (d), and 84 d in both limbs (3T MRI). Resting vastus lateralis biopsies were obtained from both limbs at baseline, 24 hours (h), 7, 28, and 84 d for mRNA abundance measurements (RT-PCR microfluidic cards). Work output was greater throughout training in ECC + CON vs CON (20.8 ± 9.7%, P < .001). Muscle CSA increased from baseline in both limbs at 28 d (CON 4.3 ± 2.6%, ECC + CON 4.0 ± 1.9%, both P < .001) and 84d (CON 3.9 ± 2.3%, ECC + CON 4.0 ± 3.1%, both P < .001), and muscle volume and isometric strength at 84 d (CON 44.8 ± 40.0%, P < .001; ECC + CON 36.9 ± 40.0%, P < .01), but no between-limb differences existed in any parameter. Ingenuity Pathway Analysis identified several cellular functions associated with regulation of muscle mass and metabolism as altered by both modalities at 24 h and 7 d, but particularly with ECC + CON. However, mRNA responses waned thereafter, regardless of modality. Initial muscle mRNA responses to training did not reflect chronic training-induced hypertrophy. Moreover, ECC + CON did not produce greater hypertrophy than CON, despite greater loading throughout and a differential mRNA response during the initial training week.

Muscle activation during leg-press exercise with or without eccentric overload

Abstract: This study sought to investigate the electromyographic activity of the vastus lateralis (VL) muscle during concentric-eccentric exercise using a new concept leg press machine enabling a preset overloading in the eccentric phase. Ten young males familiar with resistive exercise were recruited for this study. Tests were performed on a Leg-press Biostrength® (Technogym S.p.A., Italy). The load was set to 70% and 80% of one-repetition maximum (1-RM). The participants performed 2 sets of 6 repetitions at each relative load with (ECC +) and without (ISOW) an eccentric overload equivalent to 150% of the concentric load. A metronome was employed to maintain the selected cadence. Sets were separated by a 5-min rest. Surface electromyography (EMG) of VL was recorded and integrated (iEMG). Results showed a higher iEMG in ECC + with respect to ISOW at both intensities (+ 29% for 70% 1-RM, p < 0.01 and + 31% for 80% 1-RM, p < 0.001). No statistically significant differences were detected between concentric and eccentric phase in both ECC + conditions. Training with a 150% eccentric overload provides a ~ 30% greater motor unit recruitment of the VL muscle in leg press exercise. Moreover, the results show that the eccentric overloading provided by the Biostrength® machine enables training at the same level of neural activation of the concentric phase. Hence, the derecruitment of motor units, normally observed during the eccentric phase when using conventional training machines, was overcome using the Biostrength® machine; this observation seems particularly important for maximizing neuromuscular responses to strength training.

Magnetic resonance imaging based muscle strain rate mapping during eccentric contraction to study effects of unloading induced by unilateral limb suspension.

Abstract: Age- and disuse- related loss of muscle force is disproportionately larger than the loss of muscle mass. Earlier studies reported that comparing concentric and eccentric contractions, there is a significant age-related decrease in force only in concentric contractions. Magnetic Resonance Imaging enables mapping of muscle deformation and has been used to study isometric but not eccentric contractions. We report MRI based strain rate mapping of the medial gastrocnemius in subjects pre- and post-unloading induced by Unilateral Limb Suspension. In contrast to isometric contraction, no difference in strain rate indices were observed post-unloading, in conformance with preserved force during eccentric contractions.

The importance of sonographic evaluation of muscle depth and thickness prior to the 'tiny percutaneous needle biopsy'.

Abstract: Biopsy of human skeletal muscle tissue is a widely used method in many research studies, where 'the tiny percutaneous needle biopsy' (TPNB) is one of the relatively simplest and safest procedures currently available. By using and contrasting ultrasound images of vastus lateralis of young and elderly subjects, this work highlights further the safety aspects of TPNB and stresses the importance of prior ultrasound evaluation of muscle depth and thickness in order to prevent wrong muscle group or tissue sampling in subsequent laboratory analyses.

Effects Of 10-days Bed-rest On Nitric Oxide Metabolites And Microvascular Function Assessed By Near-infrared Spectroscopy: 2819 Board #280 May 29 10:30 AM - 12:00 PM

Abstract: RESULTS: PF was associated with a selective increase in VA flow during the most marked gravitational transition from microto hypergravity (P < 0.05). Increases in oxidative-nitrosative stress, glio-vascular GFAP and S100ß were observed after PF (P > 0.05), the latter proportional to the increase in VA flow, whereas biomarkers of neuronal-axonal damage (neuron-specific enolase, neurofilament light-chain, ubiquitin carboxy-terminal hydrolase L1 and tau) remained stable (P > 0.05). CONCLUSION: Collectively, these data are the first to demonstrate that acute gravitational transitions result in minor BBB disruption due to the combined effects of hemodynamic-molecular stress thereby proposing an alternative candidate mechanism and biomarkers for the reported neurological sequelae underlying SANS.

The Impairment Of Oxidative Metabolism After 10-day Of Bed Rest Is Upstream Of Skeletal-Muscle Mitochondria: 606 Board #3 May 27 1:00 PM - 3:00 PM

Abstract: METHODS: Primary skeletal muscle cells derived from the Rectus abdominis muscle of healthy active eighteen and sixty-nine year old men (SKM18M and SKM69M, respectively) were obtained from Cook MyoSite Inc. (Pittsburgh, PA). Cells were stained with MitoTracker Red (Cell Signaling; Danvers, MA) and mitochondria morphology was observed using a Zeiss LSM 710 AxioObserver confocal scanning microscope (Carl Zeiss; White Plains, NY). The mitochondrial network was analyzed using the Mitochondrial Network Analysis tool in ImageJ (MiNA, FIJI) to estimate mitochondrial footprint from a binarized image. Oxygen consumption rates were measured in intact cells using Seahorse Cell Mito Stress Tests on a XFp extracellular flux analyzer (Agilent Technologies; Santa Clara, CA). RESULTS: Primary cells derived from the young donor (SKM18M) had a larger mitochondrial footprint, longer branch length, and a greater number of network branches compared to SKM69M (Footprint: 34.65 ± 25.30 vs. 11.64 ± 9.53 μm; Branch Length: 20.59 ± 7.23 vs. 12.10 ± 6.84 μm; Network: 17.25 ± 0.16 vs. 7.67 ± 4.97 counts). SKM18M also showed higher Basal and Maximal OCR compared to SKM69M (Basal: 38.78 ± 8.34 vs. 12.82 ± 2.07; Maximal: 60.09 ±10.84 vs. 20.52 ± 2.36 pmol/min/protein). CONCLUSIONS: We observed differences morphologically and metabolically between the primary skeletal muscle cells derived from young and old donors. These preliminary results give us an insight into human skeletal muscle-derived cellular physiological capacity. Technology to observe human muscle mitochondrial fragmentation in vitro will help us elucidate the effects of aging on skeletal muscle mitochondrial fragmentation and loss of metabolic flexibility in aging.