Window into the Aging Process: Skin Proteoglycans

描述（由申请人提供）： 很明显，2岁、20岁、50岁和70岁的皮肤具有不同的物理特性，例如弹性。年轻、成熟和老年皮肤的组织学结构同样明显不同。除了真皮的细胞复杂性之外，这种间充质组织由其复杂的细胞外基质支配和区分。这种基质具有独特的组成和组织，其物理性质决定了真皮的整体性质。因此，为了了解皮肤如何随年龄变化，有必要确定关键细胞外基质成分的年龄相关变化。由于蛋白聚糖可以影响组织的弹性，可以与其他基质分子相互作用，并可以影响细胞行为，因此该建议侧重于皮肤的主要蛋白聚糖，核心蛋白聚糖和多功能蛋白聚糖。我们的数据表明，核心蛋白聚糖和多功能蛋白聚糖可以作为皮肤年龄的指标。因此，我们的工作假设是，蛋白聚糖的模式可以用来评估皮肤的体外制剂的年龄等效性。我们进一步假设，皮肤蛋白聚糖的年龄相关变化参与了皮肤生物学的年龄相关差异。为了验证这一假设，我们提出了以下具体目标的实验：具体目标1：详细分析体内人类皮肤蛋白聚糖的年龄相关变化。具体目标2：分析皮肤生物学中蛋白聚糖催化剂的年龄相关差异的作用。具体目标3：人皮肤蛋白多糖的年龄相关差异作为重建人皮肤培养物年龄等效性的指标的应用。通过这些研究，将深入了解调节皮肤细胞外基质中与年龄相关的变化的因素，从而有助于皮肤老化。

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.