Stiffening of the Extracellular Matrix Contributes to Age-Related Muscle Impairment
In this interesting open access paper, the authors explore the contribution of changes in the extracellular matrix to the deterioration of muscle function that takes place with aging. The extracellular matrix is produced and maintained by cells, and gives tissue its structural properties. It is a complex arrangement of molecules such as collagen and elastin, continually updated by cells, and not always for the better as aging progresses. Chronic inflammation, for example, provokes excessive and inappropriate deposition of collagen. Further, elastin molecules tend not be replaced at the same pace as they are damaged or broken down. In addition, persistent cross-links form between extracellular matrix molecules, altering structural properties such as elasticity. This is most apparent in skin and blood vessels, but, as the researchers here point out, these are not the only places in the body in which changes in the extracellular matrix are important.
In humans, the stiffness of the muscle-tendon complex in situ increases with aging, and this is mainly attributed to an increase in muscle stiffness, while tendons display greater compliance. Importantly, the age-related increase in stiffness of the muscle-tendon complex has been considered relevant to the preservation of eccentric force in the elderly. Whole muscle stiffness depends on the mechanical properties of muscle fibers and of extracellular matrix (ECM), and it is still debated whether muscle fibers or 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 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 sarcomere lengths. 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.