title: Rapamycin Attenuates Age-associated Changes in Tibialis Anterior Tendon Viscoelastic Properties.
abstract: Rapamycin extends mouse life span, but the extent to which rapamycin prevents aging-associated changes in specific tissues remains unclear. Stiffness increases and collagen turnover decreases in mouse tendon with aging; thus, our aim was to determine the effect of long-term rapamycin treatment on the mechanical and structural properties of tendons from old mice. Tendons were harvested from female UM-HET3 mice maintained on a standard chow diet for 4 (adult) or 22 (old) months or fed chow containing polymer-encapsulated rapamycin (eRAPA) from 9 to 22 months of age (old RAPA). Stiffness was twofold higher for tendons of old compared with adult mice, but in old RAPA mice, tendon stiffness was maintained at a value not different from that of adults. Additionally, expression of collagen decreased, expression of matrix metalloproteinase-8 increased, and total hydroxyproline content trended toward decreased levels in tendons of old eRAPA-fed mice compared with controls. Finally, age-associated calcification of Achilles tendons and accompanying elevations in expression of chondrocyte and osteoblast markers were all lower in old eRAPA-fed mice. These results suggest that long-term administration of rapamycin alters the molecular pathways responsible for aging of tendon extracellular matrix, resulting in tissue that is structurally and mechanically similar to tendons in adult mice.
authors.affiliation: Department of Biomedical Engineering.
authors.forename: Lauren Wood
authors.initials: LW
authors.lastname: Zaseck
authors.affiliation: Department of Pathology, and.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Miller
authors.affiliation: Department of Biomedical Engineering, Department of Molecular and Integrative Physiology, The University of Michigan, Ann Arbor. svbrooks@umich.edu.
authors.forename: Susan V
authors.initials: SV
authors.lastname: Brooks
mesh_terms: D000375:Aging / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D000818:Animals; D001696:Biomechanical Phenomena / Q000187:drug effects / Q000502:physiology; D003094:Collagen / Q000378:metabolism*; D004548:Elasticity / Q000187:drug effects / Q000502:physiology; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D005260:Female; D006909:Hydroxyproline / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000378:metabolism / Q000494:pharmacology; D000069451:Long Term Adverse Effects / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D020784:Matrix Metalloproteinase 8 / Q000378:metabolism; D051379:Mice; D018482:Muscle, Skeletal / Q000503:physiopathology; D020123:Sirolimus / Q000378:metabolism / Q000494:pharmacology; D013710:Tendons / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology
chemical_list: D007166:Immunosuppressive Agents; D003094:Collagen; D020784:Matrix Metalloproteinase 8; D006909:Hydroxyproline; D020123:Sirolimus
keywords: Biology of aging; Mice; mTOR
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