scholarly journals Intrinsic stiffness of extracellular matrix increases with age in skeletal muscles of mice

2014 ◽  
Vol 117 (4) ◽  
pp. 363-369 ◽  
Author(s):  
Lauren K. Wood ◽  
Erdan Kayupov ◽  
Jonathan P. Gumucio ◽  
Christopher L. Mendias ◽  
Dennis R. Claflin ◽  
...  

Advanced age is associated with increases in muscle passive stiffness, but the contributors to the changes remain unclear. Our purpose was to determine the relative contributions of muscle fibers and extracellular matrix (ECM) to muscle passive stiffness in both adult and old animals. Passive mechanical properties were determined for isolated individual muscle fibers and bundles of muscle fibers that included their associated ECM, obtained from tibialis anterior muscles of adult (8–12 mo old) and old (28–30 mo old) mice. Maximum tangent moduli of individual muscle fibers from adult and old muscles were not different at any sarcomere length tested. In contrast, the moduli of bundles of fibers from old mice was more than twofold greater than that of fiber bundles from adult muscles at sarcomere lengths >2.5 μm. Because ECM mechanical behavior is determined by the composition and arrangement of its molecular constituents, we also examined the effect of aging on ECM collagen characteristics. With aging, muscle ECM hydroxyproline content increased twofold and advanced glycation end-product protein adducts increased threefold, whereas collagen fibril orientation and total ECM area were not different between muscles from adult and old mice. Taken together, these findings indicate that the ECM of tibialis anterior muscles from old mice has a higher modulus than the ECM of adult muscles, likely driven by an accumulation of densely packed extensively crosslinked collagen.

2020 ◽  
Vol 21 (11) ◽  
pp. 3992 ◽  
Author(s):  
Piero Pavan ◽  
Elena Monti ◽  
Michela Bondí ◽  
Chenglei Fan ◽  
Carla Stecco ◽  
...  

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.


2015 ◽  
Vol 118 (5) ◽  
pp. 613-623 ◽  
Author(s):  
Irina V. Ogneva ◽  
V. Gnyubkin ◽  
N. Laroche ◽  
M. V. Maximova ◽  
I. M. Larina ◽  
...  

Altered external mechanical loading during spaceflights causes negative effects on muscular and cardiovascular systems. The aim of the study was estimation of the cortical cytoskeleton statement of the skeletal muscle cells and cardiomyocytes. The state of the cortical cytoskeleton in C57BL6J mice soleus, tibialis anterior muscle fibers, and left ventricle cardiomyocytes was investigated after 30-day 2- g centrifugation (“2- g” group) and within 12 h after its completion (“2- g + 12-h” group). We used atomic force microscopy for estimating cell's transverse stiffness, Western blotting for measuring protein content, and RT-PCR for estimating their expression level. The transverse stiffness significantly decreased in cardiomyocytes (by 16%) and increased in skeletal muscles fibers (by 35% for soleus and by 29% for tibialis anterior muscle fibers) in animals of the 2-g group (compared with the control group). For cardiomyocytes, we found that, in the 2- g + 12-h group, α-actinin-1 content decreased in the membranous fraction (by 27%) and increased in cytoplasmic fraction (by 28%) of proteins (compared with the levels in the 2- g group). But for skeletal muscle fibers, similar changes were noted for α-actinin-4, but not for α-actinin-1. In conclusion, we showed that the different isoforms of α-actinins dissociate from cortical cytoskeleton under increased/decreased of mechanical load.


2000 ◽  
Vol 113 (20) ◽  
pp. 3583-3591 ◽  
Author(s):  
M. Fluck ◽  
V. Tunc-Civelek ◽  
M. Chiquet

Tenascin-C and tenascin-Y are two structurally related extracellular matrix glycoproteins that in many tissues show a complementary expression pattern. Tenascin-C and the fibril-associated minor collagen XII are expressed in tissues bearing high tensile stress and are located in normal skeletal muscle, predominantly at the myotendinous junction that links muscle fibers to tendon. In contrast, tenascin-Y is strongly expressed in the endomysium surrounding single myofibers, and in the perimysial sheath around fiber bundles. We previously showed that tenascin-C and collagen XII expression in primary fibroblasts is regulated by changes in tensile stress. Here we have tested the hypothesis that the expression of tenascin-C, tenascin-Y and collagen XII in skeletal muscle connective tissue is differentially modulated by mechanical stress in vivo. Chicken anterior latissimus dorsi muscle (ALD) was mechanically stressed by applying a load to the left wing. Within 36 hours of loading, expression of tenascin-C protein was ectopically induced in the endomysium along the surface of single muscle fibers throughout the ALD, whereas tenascin-Y protein expression was barely affected. Expression of tenascin-C protein stayed elevated after 7 days of loading whereas tenascin-Y protein was reduced. Northern blot analysis revealed that tenascin-C mRNA was induced in ALD within 4 hours of loading while tenascin-Y mRNA was reduced within the same period. In situ hybridization indicated that tenascin-C mRNA induction after 4 hours of loading was uniform throughout the ALD muscle in endomysial fibroblasts. In contrast, the level of tenascin-Y mRNA expression in endomysium appeared reduced within 4 hours of loading. Tenascin-C mRNA and protein induction after 4–10 hours of loading did not correlate with signs of macrophage infiltration. Tenascin-C protein decreased again with removal of the load and nearly disappeared after 5 days. Furthermore, loading was also found to induce expression of collagen XII mRNA and protein, but to a markedly lower level, with slower kinetics and only partial reversibility. The results suggest that mechanical loading directly and reciprocally controls the expression of extracellular matrix proteins of the tenascin family in skeletal muscle.


Metabolism ◽  
1987 ◽  
Vol 36 (8) ◽  
pp. 761-767 ◽  
Author(s):  
Maggie M.-Y. Chi ◽  
Carol S. Hintz ◽  
Deidre McKee ◽  
Steven Felder ◽  
Natasha Grant ◽  
...  

2017 ◽  
Vol 312 (1) ◽  
pp. C16-C28 ◽  
Author(s):  
D. Randazzo ◽  
B. Blaauw ◽  
C. Paolini ◽  
E. Pierantozzi ◽  
S. Spinozzi ◽  
...  

We recently reported that skeletal muscle fibers of obscurin knockout (KO) mice present altered distribution of ankyrin B (ankB), disorganization of the subsarcolemmal microtubules, and reduced localization of dystrophin at costameres. In addition, these mice have impaired running endurance and increased exercise-induced sarcolemmal damage compared with wild-type animals. Here, we report results from a combined approach of physiological, morphological, and structural studies in which we further characterize the skeletal muscles of obscurin KO mice. A detailed examination of exercise performance, using different running protocols, revealed that the reduced endurance of obscurin KO animals on the treadmill depends on exercise intensity and age. Indeed, a mild running protocol did not evidence significant differences between control and obscurin KO mice, whereas comparison of running abilities of 2-, 6-, and 11-mo-old mice exercised at exhaustion revealed a progressive age-dependent reduction of the exercise tolerance in KO mice. Histological analysis indicated that heavy exercise induced leukocyte infiltration, fibrotic connective tissue deposition, and hypercontractures in the diaphragm of KO mice. On the same line, electron microscopy revealed that, in the diaphragm of exercised obscurin KO mice, but not in the hindlimb muscles, both M-line and H-zone of sarcomeres appeared wavy and less defined. Altogether, these results suggest that obscurin is required for the maintenance of morphological and ultrastructural integrity of skeletal muscle fibers against damage induced by intense mechanical stress and point to the diaphragm as the skeletal muscle most severely affected in obscurin-deficient mice.


1990 ◽  
Vol 4 (1) ◽  
pp. 55-63 ◽  
Author(s):  
Jill K. Manchester ◽  
Maggie M.‐Y. Chi ◽  
Beverly Norris ◽  
Bernard Ferrier ◽  
Igor Krasnov ◽  
...  

Author(s):  
Renato Rissi ◽  
George Azevedo Lemos ◽  
Bernardo Neme Ide ◽  
Rafael Ludemann Camargo ◽  
Renato Chaves Souto Branco ◽  
...  

DOI: http://dx.doi.org/10.5007/1980-0037.2016v18n1p1 Although it is a widely used resource for the treatment of musculoskeletal injuries, immobilization causes deleterious effects in muscle tissue after a short period of time. This study aimed to evaluate the gastrocnemius and tibialis anterior muscles of obese and protein malnourished animals under joint immobilization condition. Overall, 28 adult male mice were used (C57 / BL6), being divided into four groups (N = 7): Control Group (CG), Immobilized Control Group (ICG), Immobilized Obese Group (IOG) and Immobilized Malnourished Group (IMG). The immobilization protocol was performed by the use of adhesive tape and plaster. The conditions and obesity and protein malnutrition have been developed through the ingestion of diets specific for each group of animals. The histomorphometric analysis of muscles evaluated area and the diameter of muscle fibers. All immobilized groups showed reduction in the area and diameter of muscle fibers when compared to GC. Comparisons among immobilized groups showed that the area and diameter of muscle fibers of IOG and IMG were lower than ICG. The immobilization protocol caused reduction in muscle trophism in animals, and obese and malnourished animals suffered high losses under condition of muscle atrophy. 


1987 ◽  
Vol 57 (6) ◽  
pp. 1730-1745 ◽  
Author(s):  
S. C. Bodine ◽  
R. R. Roy ◽  
E. Eldred ◽  
V. R. Edgerton

In 11 tibialis anterior muscles of the cat, a single motor unit was characterized physiologically and subsequently depleted of its glycogen through repetitive stimulation of an isolated ventral root filament. Muscle cross sections were stained for glycogen using a periodic acid-Schiff reaction, and single-fiber optical densities were determined to identify those fibers belonging to the stimulated motor unit. Innervation ratios were determined by counting the total number of muscle fibers in a motor unit in sections taken through several levels of the muscle. The average innervation ratios for the fast, fatigueable (FF) and fast, fatigue-resistant (FR) units were similar. However, the slow units (S) contained 61% fewer fibers than the fast units (FF and FR). Muscle fibers belonging to S and FR units were similar in cross-sectional area, whereas fibers belonging to FF units were significantly larger than fibers belonging to either S or FR units. Additionally, muscle fibers innervated by a single motoneuron varied by two- to eightfold in cross-sectional area. Specific tensions, based on total cross-sectional area determined by summing the areas of all muscle fibers of each unit, showed a modest difference between fast and slow units, the means being 23.5 and 17.2 N X cm-2, respectively. Variations in maximum tension among units could be explained principally by innervation ratio, although fiber cross-sectional area and specific tension did contribute to differences between unit types.


1993 ◽  
Vol 70 (4) ◽  
pp. 1300-1306 ◽  
Author(s):  
R. Bakels ◽  
D. Kernell

1. Properties of single motoneuron/muscle-unit combinations were determined for tibialis anterior (TA) in rats anesthetized with pentobarbital. The TA observations were systematically compared with those obtained earlier by the use of the same techniques from rat medial gastrocnemius (MG). 2. TA motoneurons were investigated with regard to afterhyperpolarization (AHP; total duration 32-74 ms, amplitude 0.39-4.96 mV) and axonal conduction velocity (41-79 m/s). TA muscle-unit measurements included the time course of the isometric twitch (time-to-peak force 10.8-18.0 ms; total duration 42-92 ms), the maximum tetanic force (22-217 mN), and a measure of fatigue sensitivity (fatigue index 5-100%). The range of twitch and AHP durations ("speed range") was markedly smaller in the present TA material than for MG. 3. The mean duration of the TA motoneuronal AHP (49 +/- 8 ms, mean +/- SD) was close to that of its muscle-unit twitch (56 +/- 12 ms). Thus an "average" speed match existed between TA motoneurons and their muscle fibers. 4. For TA there was no correlation between the time courses of AHP and twitch. Thus there was for TA no "continuous" speed match between the motoneurons and their muscle fibers. 5. For TA twitches or AHPs studied separately, there was a significant correlation between different time course measures. Furthermore, compared with TA units having relatively fast twitches, those with slower twitches tended to show 1) a smaller maximum tetanic force and 2) a greater AHP amplitude. Fatigue-resistant units tended to have slower twitches than fatigue-sensitive ones.(ABSTRACT TRUNCATED AT 250 WORDS)


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