Characterizing proteome changes leading to aging in the African killifish

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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.