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 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.

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