Age- and gender-dependent changes in connective tissue remodeling: physiological differences in circulating MMP-3, MMP-10, TIMP-1 and TIMP-2 level

Gerontology. 2011;57(1):44-52. doi: 10.1159/000295775. Epub 2010 Mar 9.

Abstract

Background: the mechanisms which cause age-dependent remodeling of connective tissue are still not fully understood. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) constitute an important proteolytic pathway affecting physiological matrix remodeling.

Objective: the way in which changes in the extracellular matrix metabolism during the ageing process influence the level of circulating MMP-3 and MMP-10, as well as their tissue inhibitors TIMP-1 and TIMP-2, in a healthy population was investigated in this study.

Methods: blood samples were taken from 81 healthy individuals aged 6-62 years and measured for MMP-3, MMP-10, TIMP-1 and TIMP-2 levels using enzyme-linked immunosorbent assays. Polyacrylamide gel electrophoresis followed by Western immunoblotting allowed for the detection of pro- and active forms of both MMPs.

Results: Serum MMP-3 and TIMP-1 values were positively correlated with age (r = 0.44, p = 0.00001 and r = 0.28, p = 0.012, respectively). A contrary tendency was found for MMP-10 and TIMP-2 serum levels. A strong age-related decrease in MMP-10 (-0.53; p = 0.000) and TIMP-2 (-0.52; p = 0.000) was noticed in our study. Gender was a significant factor modifying MMP/TIMP potential, except for the MMP-10 level.

Conclusions: the data presented indicate that changes in MMP/TIMP balance occur in physiological ageing. Moreover, these findings highlight the necessity of utilizing age- and sex-matched values for analysis of MMPs and TIMPs in the pathological conditions.

MeSH terms

  • Adolescent
  • Adult
  • Aging / blood*
  • Aging / physiology*
  • Child
  • Connective Tissue / physiology*
  • Female
  • Humans
  • Male
  • Matrix Metalloproteinase 10 / blood*
  • Matrix Metalloproteinase 3 / blood*
  • Middle Aged
  • Reference Values
  • Sex Characteristics
  • Tissue Inhibitor of Metalloproteinase-1 / blood*
  • Tissue Inhibitor of Metalloproteinase-2 / blood*
  • Young Adult

Substances

  • Tissue Inhibitor of Metalloproteinase-1
  • Tissue Inhibitor of Metalloproteinase-2
  • MMP3 protein, human
  • Matrix Metalloproteinase 3
  • MMP10 protein, human
  • Matrix Metalloproteinase 10