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

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.