AGE-RELATED DIFFERENCES IN THE TEMPORAL AND SPATIAL REGULATION OF MATRIX METALLOPROTEINASES (MMPS) IN NORMAL SKIN AND ACUTE CUTANEOUS WOUNDS OF HEALTHY HUMANS

Despite the association of increasing age with chronic wound-healing d isorders and an impaired rate of healing of acute cutaneous wounds, th e role of matrix metalloproteinases (MMPs) is unknown. To determine th e spatial and temporal patterns and activities of MMP-1, -2, -3 and -9 , 132 healthy humans aged between 19 and 96 years underwent 4-mm punch biopsies followed by wound excision between day 1 and day 180 postwou nding. Wounds showed an age-related increase in MMP-2 and MMP-9 immuno staining from day 3; this was associated with degradation of gelatin a s shown by zymograms and with increased proteinase activity as shown b y azocoll assays. Distinct spatial localisations for each MMP were obs erved: MMP-2 was found in epidermal structures; MMP-9 was observed in inflammatory cells up to day 21; MMP-1 was localised to keratinocytes at the wound margin. Normal old skin showed pro-MMP-2 bands on zymogra phy and increased MMP-2 immunostaining. These results indicate that: ( 1) intrinsic ageing is associated with the up-regulation of MMPs previ ously associated with chronic wound healing; (2) wound-tissue proteina ses are essentially active up to day 21 postwounding; and (3) intrinsi c ageing may predispose to tissue breakdown disorders because of MMP-2 up-regulation in normal skin.