Window into the Aging Process: Skin Proteoglycans

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DESCRIPTION (provided by applicant): It is clear that the skin of a 2-year-old, a 20-year-old, a 50-year-old, and a 70-year-old has different physical properties, such as resiliency. The histologic structure of young, mature, and old skin is likewise clearly different. In addition to the cellular complexity of the dermis, this mesenchymal tissue is dominated and distinguished by its complex extracellular matrix. This matrix has a unique composition and organization, and its physical properties determine the overall properties of the dermis. Thus, in order to understand how skin changes as a function of age, it is necessary to determine the age-related changes in key extracellular matrix components. Because proteoglycans can affect the resiliency of a tissue, can interact with other matrix molecules, and can influence cell behavior, this proposal focuses on the major proteoglycans of skin, decorin and versican. Our data suggest that decorin and versican can serve as indicators of skin age. Hence, our working hypothesis is that the pattern of proteoglycans can be used to evaluate the age equivalence of in vitro formulations of skin. We further hypothesize that age-related changes in skin proteoglycans are involved in age-related differences in skin biology. To test this hypothesis, we propose experiments focused on the following Specific Aims: Specific Aim 1: Detailed analysis of age-related changes in human skin proteoglycans in vivo. Specific Aim 2: Analysis of the role of age-related differences in proteoglycan catabolism in skin biology. Specific Aim 3: Application of the age-related differences in human skin proteoglycans as an indicator of the age equivalence of cultures of reconstructed human skin. With these studies, insight will be gained into the factors which regulate age-related changes in skin extracellular matrix and, hence, which contribute to the aging of skin.