LYSOSMAL PROTEASES, PROTEIN TURNOVER AND AGING

我们建议检验蛋白质周转率 随着年龄的增长而下降，这导致了改变的积累， proteins. 作为模式生物，我们用土壤线虫 秀丽隐杆线虫 我们已经纯化了组织蛋白酶D， 提出纯化和表征溶酶体组织蛋白酶L。 我们将隔离 突变体，无论是缺陷和超生产，影响这两个 蛋白酶，并使用它们来确定单个蛋白酶在 蛋白质周转，包括整体蛋白质和特定测试蛋白质。 我们 也在设计蛋白酶抑制剂的输送系统， 可用于确认突变体的结果。 最后我们将 评估蛋白质周转率的变化， 老化，并确定是否调节蛋白酶活性和/或蛋白质 体内周转影响C. elegans，使用a 多参数衰老指数

We propose to test the hypothesis that the rate of protein turnover declines with age, and that this leads to an accumulation of altered proteins. As a model organism, we are using the soil nematode Caenorhabditis elegans. We have already purified Cathepsin D, and now propose to purify and characterize lysosomal Cathepsin L. We will isolate mutants, both deficient and hyperproducing, affecting both of these proteases, and use them to determine the role of individual proteases in protein turnover, both of global protein and of specific test proteins. we are also designing delivery systems for protease inhibitors, so that these can be used to confirm results obtaine with mutants. Finally, we will assess the changes in the rate of protein turnover which occur during aging, and determine whether modulation of protease activity and/or protein turnover in vivo affects the rate of aging of C. elegans, using a multiparametric index of senescence.