Production of the Tissue Inhibitor of Metalloproteinase‐2 (TIMP‐2) and Evaluation of Its Potential as Anti‐Aging Active

Abstract

Collagen‐degrading matrix metalloproteinases (MMPs) show increased activities predominantly in UV‐irradiated skin as well as in chronologically aged skin. MMPs are therefore reasoned to be associated with the degenerative alterations in the collagenous dermal extracellular matrix, which in turn may accelerate the signs of skin aging such as wrinkle formation and skin sagging. In normal physiological processes MMP activity is controlled by the endogenous tissue inhibitors of metalloproteinases (TIMPs). Here we report the biotechnological production of the human‐identical inhibitor TIMP‐2 and its evaluation as an anti‐aging active through attenuation of the degenerative MMP activity. The recombinant TIMP‐2 polypeptide selectively inhibited MMPs in vitro which are involved in aging processes and showed efficient IC50 values in the low nanomolar range. Topical application of formulated TIMP‐2 on skin explants with subsequent UVB irradiation (2‐3 MED) resulted in an almost quantitative protection against collagen degradation. Thus, our biotechnological production of TIMP‐2 leads to the active broad‐spectrum MMP inhibitor that reduces excessive MMP activity and thereby preserves the structural integrity of collagen network.A poster of this work was presented at the 23rd IFSCC Congress 2004, Orlando, Florida, USA.