1025 Onset, rate, and progression of human dermal extracellular matrix aging

Abstract

Decrease in mass and accumulation of damage are hallmarks of aging in all organs. Human dermis is primarily composed of densely-packed bundles of collagen fibrils, which contain mostly type I/type III collagens. We have quantitatively assessed age-related alterations of human dermal collagen fibrils from 60 healthy volunteers aged 20 to 92 years (mean age, 54 years), composed of 29 females and 31 males. Skin samples were obtained from sun-protected buttocks. During aging, collagen content is reduced and collagen fibril fragmentation increases, due to downregulation of type I (COLI) and type III (COLIII) procollagen and elevated matrix metalloproteinase-1 (MMP1) expression, respectively. COLI and COLIII expression decreases by approximately 84% and 80%, respectively, from ages 20 to 80 years (p<0.05, moderately strong linear correlation with age). MMP-1 expression and resultant collagen fibril fragmentation increase 8-fold and 2.9-fold, respectively, from ages 20 to 80 years (p<0.05, strong linear correlation with age). MMP-mediated fragmentation disrupts the three-dimensional organization of collagen fibrils. Nano-scale atomic force microscopy revealed that collagen fibrils become progressively disorganized with age. Average fibril surface roughness (Ra) increased 2.2-fold during aging (p<0.05, strong linear correlation with age). Statistical predictive modeling indicated that the rates of age-related alterations of collagen metabolism and structure begin to accelerate early in the fourth decade of life, continue to increase through the sixth decade, and taper to a nearly constant level through the seventh and eighth decades. The above data delineate the temporal relationships between aging and molecular alterations that cause decreases in dermal mass and accumulation of dermal damage. This knowledge provides a foundation for evaluating the benefits of dietary, life-style, or pharmacological interventions aimed at reducing the rate of skin aging and improving the health of skin during aging.