HUMAN AGING IMPAIRS INJURY-INDUCED IN-VIVO EXPRESSION OF TISSUE INHIBITOR OF MATRIX METALLOPROTEINASES (TIMP)-1 AND (TIMP)-2 PROTEINS AND MESSENGER-RNA

Proteolysis is an essential component of wound healing hut, if uncontr olled, it may lead to degradation of the neo-matrix and a delay in mou nd repair, Despite numerous reports of impaired mound healing associat ed with increasing age, the control of proteolysis is completely unkno wn, Tissue inhibitor of matrix metalloproteinases (TIMP)-1 and -2 inhi bit the activity of matrix metalloproteinases and the pattern of regul ation of these molecules determines in part the spatial and temporal r egulation of proteolytic activity, This study reports on TIMP-1 and -2 protein localization using immunocytochemistry in healing mounds of h ealthy subjects of different ages from day 1 to 6 months post-wounding , and has quantified the mRNA levels for both inhibitors using release transcriptase-polymerase chain reaction (RT-PCR), TIMP-1 and TIMP-2 p roteins are up-regulated from 24 h post-wounding, with a decrease in s taining intensity by day 7 for TIMP-2 and by day 14 for TIMP-1. Steady -state mRNA levels for both TIMPs were significantly greater in normal young skin than in aged skin, In the young, there was a significant i ncrease in mRNA expression for TIMP-1 and -2 by day 3 post-wounding, w hich decreased by day 14 and had returned to basal levels at day 21, I n the wounds of the aged subjects, basal levels were observed for TIMP -1 and -2 at all time-points, These results suggest that intrinsic cut aneous ageing is associated with reduced levels of TIMP mRNA both in n ormal skin and during acute wound repair, These levels may be instrume ntal in dermal tissue breakdown in normal skin, retarded wound healing , and the predisposition of the elderly to chronic wound healing state s, (C) 1997 John Wiley & Sons, Ltd.