Rapamycin Attenuates Age-associated Changes in Tibialis Anterior Tendon Viscoelastic Properties

J Gerontol A Biol Sci Med Sci. 2016 Jul;71(7):858-65. doi: 10.1093/gerona/glv307. Epub 2016 Jan 24.

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.

Keywords: Biology of aging; Mice; mTOR.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aging* / drug effects
  • Aging* / pathology
  • Aging* / physiology
  • Animals
  • Biomechanical Phenomena* / drug effects
  • Biomechanical Phenomena* / physiology
  • Collagen / metabolism*
  • Elasticity* / drug effects
  • Elasticity* / physiology
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / metabolism
  • Extracellular Matrix / physiology
  • Female
  • Hydroxyproline / metabolism
  • Immunosuppressive Agents / metabolism
  • Immunosuppressive Agents / pharmacology
  • Long Term Adverse Effects* / etiology
  • Long Term Adverse Effects* / pathology
  • Long Term Adverse Effects* / physiopathology
  • Matrix Metalloproteinase 8 / metabolism
  • Mice
  • Muscle, Skeletal / physiopathology
  • Sirolimus* / metabolism
  • Sirolimus* / pharmacology
  • Tendons* / metabolism
  • Tendons* / pathology
  • Tendons* / physiopathology

Substances

  • Immunosuppressive Agents
  • Collagen
  • Matrix Metalloproteinase 8
  • Hydroxyproline
  • Sirolimus