The Role Of Collagen Composition And Orientation In Lateral Force Transmission With Aging

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PURPOSE: Collagen is the most abundant protein in the body and functions to provide the mechanical strength of connective tissues. In muscle, collagen fibrils function both to hold muscle fibers together and transmit force laterally between fibers. With aging, force transmission is reduced; however, how changes to specific collagen isoforms or the matrix orientation contribute to force loss is currently unclear. The current study was designed to compare lateral force transmission in the gastrocnemius muscle of young and old people with changes in specific collagen proteins and the orientation of the matrix. METHODS: The calf strength of 12 subjects, 5 between 18 and 30 years old and 7 over the age of 65, was measured within an MRI. Images were taken to determine lateral force transmission. Following strength testing, biopsies were obtained under local anesthetic from the gastrocnemius muscle. Biopsies were pinned to cork at resting length and frozen in isopentane cooled in liquid nitrogen. Cross-sections were taken to determine collagens I, III, IV, and V content, whereas longitudinal sections were stained with picrosirius red to determine matrix orientation. The collagen IV image was also used to determine muscle fiber cross-sectional area (CSA). RESULTS: Collagen I and V were evenly dispersed throughout the cross-sections, whereas Collagen IV and VI were densest around individual muscle fibers. Collagen IV content was similar in young and old. As expected, fiber CSA tended (p = 0.1) to decrease in the old subjects. Picrosirius red staining showed that the collagen matrix is oriented at a 22.3±3.1% angle to the fibers in young and 30.2±8.7% in old subjects. CONCLUSIONS: Preliminary data suggests that, in the old, fiber CSA decreases and the extracellular matrix becomes less aligned. By establishing the role of specific collagen proteins during aging, we hope to better understand the relationship between the extracellular matrix and force transmission in muscle and how this relationship is modified by age.