Abstract B024: Increasing cellular longevity in budding yeast by activating the Anaphase Promoting Complex
Bibliographic record
Abstract
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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".