Abstract

Introduction: Caloric restriction and rapamycin extend longevity in mammals (reviewed by Cox 2009), but these interventions may impair wound healing (Reed1996; Ekici 2007). Wound healing requires collagen, the predominant matrix component in skin and other organs. Using collagen from murine tail tendons, this project examined the effect of short-term exposure to caloric restriction and rapamycin on tail collagens of aged mice. Methods: Aged mice were exposed for 10 weeks (short-term) to 40% caloric restriction (n=6), 2.24mg/kg rapamycin (n=6), or usual diet (n=4). Mice were euthanized at 28-months, and collagen was extracted from mice tails. Results: -Caloric-restriction and rapamycin collagens aggregated into fibrils less effectively and formed less dense, more disorganized gels than collagens from control mice. -Caloric-restriction collagen was contracted by dermal fibroblasts to a greater extent than control mice collagen. -Fibroblasts cultured for 5 days within caloric-restriction and rapamycin collagens displayed lower cell count than those in control collagen. -α2 integrin, a receptor that mediates fibroblast-collagen matrix interactions, was more highly expressed in control collagen than caloric-restriction collagen. Conclusions: Although the collagens appeared similar by SDS PAGE electrophoresis, there were significant alterations in collagen organization. Collagen from aged mice that have received short-term caloric restriction or rapamycin display impaired capacity to polymerize into a 3D matrix. Human dermal fibroblasts placed in the collagens demonstrated differences in behavior and biosynthesis of related extracellular matrix proteins. These data show that short-term caloric-restriction and rapamycin interventions alter collagen’s structural properties and influence fibroblast behaviors in a manner that might impair wound healing.