Abstract B024: Increasing cellular longevity in budding yeast by activating the Anaphase Promoting Complex

Abstract The Anaphase Promoting Complex (APC), a large and highly conserved ubiquitin ligase, is involved in genome stability, resistance to cancer progression, and has an important role in promoting health and lifespan. While best known for its function during the events of the cell cycle, the APC also has important roles outside of mitosis in aging cells. Understanding changes in function of the APC, and how these changes can be optimized, may increase our knowledge of cellular longevity and how it can be enhanced. We hypothesize that the APC loses function with age, and that the introduction of biological activators may aid to rescue these effects, improving the overall health of the cell to extend longevity. The abundance of orthologous genes and pathways between eukaryotes, complemented by the relative ease of genetic manipulation, allows for rapid advancement of research by deciphering gene functions in a yeast model to predict human disease and aging. By extension, increasing cell health in multicellular organisms will ultimately enhance the health of the entire organism. A dual screen was performed in the Harkness Lab on a library of short, random peptides to identify those which reproducibly interact with APC subunits, with particular interest on those which have an affect on function. Current research has found that several of these peptides are effective at extending cellular lifespan and suppressing APC mutant phenotypes, providing a novel means of exploring APC function in aging cells. Utilizing this direct biological activation of the APC, in addition to commercially available activators that function indirectly, I aim to identify potential therapeutic agents that can increase APC activity and extend lifespan utilizing Saccharomyces cerevisiae as a model organism. Citation Format: Rachel E. Harris, Troy A. A. Harkness. Increasing cellular longevity in budding yeast by activating the Anaphase Promoting Complex [abstract]. In: Proceedings of the AACR Special Conference: Aging and Cancer; 2022 Nov 17-20; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_1):Abstract nr B024.