Characterizing proteome changes leading to aging in the African killifish

衰老与组织功能下降有关。对无脊椎动物的新研究表明，原始的蛋白质组对于防止这种下降至关重要。然而，在脊椎动物中，缺乏对蛋白质组变化及其在衰老过程中功能重要性的研究，这主要是由于目前模式生物的长寿命所致。非洲剑鱼克服了这一限制，表现出自然压缩的寿命，但表现出与衰老相关的表型。我的目标是表征蛋白质组的变化，包括蛋白质组聚集状态，在非洲千里鱼的老化过程中。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。为了达到我的目标，我将使用高精度质谱仪对非洲剑鱼不同年龄各器官的蛋白质组进行定量分析。我将创建一个数据库，让公众可以访问非洲剑鱼蛋白质组，从而为不断增长的剑鱼群落做出巨大贡献。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的重要性。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。这些实验不仅将描述脊椎动物系统中生理衰老下的蛋白质组，还将识别可以减缓甚至逆转衰老的分子变化。

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.