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.

Highlights

  • Decreases in muscle mass and strength are well established hallmarks of skeletal muscle aging

  • Within the limits of the present study, our results show that, at any given sarcomere length (SL) across the whole physiological sarcomere working range (2.5–3.3 μm), the resting passive tension is significantly higher in the bundles of the elderly compared to those of the young

  • No significant difference in passive tension was found when single fibers were compared and, the difference between the elderly and the young can be attributed to the extracellular matrix (ECM) present between the fibers composing the bundle

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Summary

Introduction

Decreases in muscle mass and strength are well established hallmarks of skeletal muscle aging. This approach has been subsequently adopted by Woods and coworkers [15], who showed that mouse tibialis anterior fibers did not change their passive mechanical properties with aging, while the increased stiffness was only due to changes in the ECM properties In contrast with those results, a recent study by Lim and coworkers [22] showed a greater passive force and modified viscoelastic properties (higher peak passive force after stretch) in isolated single muscle fibers of human Vastus Lateralis in elderly (73–87 years) compared to younger (21–40 years) subjects. We apply the same method to fibers and bundles from muscles of young subjects and compare the relative contribution of the ECM to passive tension and stiffness in the two age groups

Results
Discussion
Participants
Experimental Protocol
Histological Analysis
Tension Calculation at Each Elongation Step
Statistical Analysis
Ethics approval

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