Aging Impairs Intramuscular Collagen Remodeling Responses to Repeated Passive Stretching in Skeletal Muscle

Aging is associated with changes in intramuscular collagen structure and metabolism, which may impair mechanical adaptability and regenerative capacity. We investigated the effects of aging and repeated passive stretching on intramuscular collagen remodeling in the tibialis anterior muscles of mice. The tibialis anterior muscles of young and aged mice were exposed to repeated passive stretching, and the localization of collagen and collagen-related factors was evaluated. Baseline gene expression of collagens I and IV was significantly reduced in aged muscles and was not restored by stretching. Repeated passive stretching increased the area and intensity of collagen I immunoreactivity in both young and aged mice but produced little change in collagen IV. Stretch-induced dynamic changes in lysyl oxidase-positive cells in the extracellular matrix (ECM) were evident in young mice but were markedly attenuated in aged mice. In addition, matrix metalloproteinases (MMP2 and MMP9) mRNA and protein expressions did not differ between groups. No significant age- or stretch-dependent changes were observed in the localization of advanced glycation end products. These findings suggest that although the increase in fibrillar collagen in response to stretching is maintained with aging, the regulatory mechanisms controlling ECM stabilization, particularly those related to cross-linking dynamics, may be impaired.