COLLAGEN CROSSLINKS/TISSUE MARKERS OF COMPARATIVE AGING

为了在生物化学上确定结缔组织中衰老的标志物 关于胶原蛋白随年龄变化的几个具体假说 将测试交叉链接。我们预计，这些变化将包括： 1.含有交联剂的羟赖氨酸的减少；2. 交联度的降低，但不一定是总的降低。 3.“聚(CB-6)”的增加， 胶原蛋白特异性多肽。使用新开发的超灵敏高效液相 简约与不可约的分离与定量技术 我们将分析大鼠、人类和 不同年龄的猴子。“聚(CB-6)”将通过分析 从组织胶原蛋白中制备的CNBR多肽。通过检查两个不同的 组织(皮肤和肺)，我们将能够检验这一假设 上述“老化标志物”在胶原中同步出现。 不同的组织来源，即使数量关系可能显示 组织特异性。通过研究三个不同的物种，我们将能够 为了比较时间和生物年龄相近的受试者的胶原蛋白， 从而允许我们尝试区分相关的变化 随着时间顺序的老化和与生物老化相关的变化。 这种组织老化的生化标记物应该与 人体老年学的临床研究。

In order to biochemically define markers of aging in connective tissue several specific hypotheses concerning age-associated changes in collagen crosslinks will be tested. We predict that such changes will include: 1.\a decrease in hydroxylysine containing crosslinks; 2. a decrease in the reducibility of crosslinks, but not necessarily a decrease in the total number of such crosslinks; and 3. an increase in "poly (CB-6)", a collagen-specific peptide. Using newly developed ultra-sensitive HPLC techniques for separation and quantitation of reduced and nonreducible crosslinks, we will analyze skin and lung tissue from rats, humans, and monkeys of various ages. "Poly (CB-6)" will be quantitated by analysis of CNBr peptides prepared from tissue collagen. By examining two different tissues (skin and lung), we will be able to test the hypothesis that the "aging markers" described above occur synchronously in collagens from different tissue sources, even though quantitative relationships may show tissue specificity. By examining three different species, we will be able to compare collagens from subjects of similar temporal and biological age, thus allowing us to attempt to differentiate between changes associated with chronological aging and changes associated with biological aging. Such biochemical markers of tissue aging should have broad relevance to clinical research in gerontology in human subjects.