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Characterizing proteome changes leading to aging in the African killifish

表征导致非洲鳉鱼衰老的蛋白质组变化

基本信息

批准号：
355484764
负责人：
Dr. Katharina Papsdorf
金额：
--
依托单位：
Department of Genetics
依托单位国家：
德国
项目类别：
Research Fellowships
财政年份：
2017
资助国家：
德国
起止时间：
2016-12-31 至 2018-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/355484764?language=en
关键词：
Characterizing proteome changes leading aging

项目摘要

Aging is associated with a decline in tissue function. Emerging studies in invertebrates indicate that a pristine proteome is critical in preventing this decline. However, investigation of the proteome changes and their functional importance during aging is lacking in vertebrates, mostly due to the long lifespan of current model organisms. The African killifish overcomes this limitation by exhibiting a naturally compressed lifespan, yet displaying aging-related phenotypes. My goal is to characterize changes to the proteome, including the proteome aggregation status, during aging in the African killifish. This exciting project will be conducted in Dr. Brunets laboratory, in an interdisciplinary collaboration with Dr. Jaroszs laboratory, at Stanford University. To address my goal, I will analyze the proteome quantitatively using high precision mass spectrometry in various organs at different ages in the African killifish. I will create a database to render the African killifish proteome publicly accessible, thereby greatly contributing to the growing killifish community. I will determine the importance of specific protein changes, in particular protein aggregation, on tissue health and lifespan. Finally, I will analyze the proteome of selected organs in conditions that extend lifespan and promote rejuvenation. These experiments will not only characterize the proteome under physiological aging in a vertebrate system, but also identify molecular changes that can slow or even reverse aging.

衰老与组织功能的下降有关。在无脊椎动物中的新兴研究表明，原始蛋白质组在防止这种下降方面至关重要。然而，研究蛋白质组的变化及其功能的重要性在衰老过程中缺乏脊椎动物，主要是由于目前的模式生物寿命长。非洲鳉鱼克服了这一限制，表现出自然压缩的寿命，但显示衰老相关的表型。我的目标是表征蛋白质组的变化，包括蛋白质组聚集状态，在非洲鳉鱼老化。这个令人兴奋的项目将在Brunets博士实验室进行，与斯坦福大学的Jaroszs博士实验室进行跨学科合作。为了实现我的目标，我将使用高精度质谱法定量分析非洲鳉鱼不同年龄不同器官的蛋白质组。我将创建一个数据库，使非洲鳉鱼蛋白质组公开访问，从而大大有助于不断增长的鳉鱼社区。我将确定特定蛋白质变化的重要性，特别是蛋白质聚集，对组织健康和寿命。最后，我将分析在延长寿命和促进返老还童的条件下选定器官的蛋白质组。这些实验不仅将表征脊椎动物系统中生理老化下的蛋白质组，而且还将确定可以减缓甚至逆转衰老的分子变化。