Epithelial and Mesenchymal Cell Biology Collagen Fragmentation Promotes Oxidative Stress and Elevates Matrix Metalloproteinase-1 in Fibroblasts in Aged Human Skin

Aged human skin is fragile because of fragmentation and loss of type I collagen fibrils, which confer strength and resiliency. We report here that dermal fibroblasts express increased levels of collagen-de-grading matrix metalloproteinases-1 (MMP-1) in aged (>80 years old) compared with young (21 to 30 years old) human skin in vivo. Transcription factor AP-1 and 21 integrin, which are key regulators of MMP-1 ex-pression, are also elevated in fibroblasts in aged human skin in vivo. MMP-1 treatment of young skin in organ culture causes fragmentation of collagen fibrils and re-duces fibroblast stretch, consistent with reduced me-chanical tension, as observed in aged human skin. Limited fragmentation of three-dimensional colla-gen lattices with exogenous MMP-1 also reduces fibro