Modeling the Effect of p16 on Two Types of Senescence
Class of 2018
- Medina Senior High School, Medina Ohio, 2014
- The College of Wooster, BA in Biology, 2018
- Professional experience
Beta Beta Beta – Biology National Honor Society
Phi Alpha Theta – History National Honor Society
Pre-Health Club Co-President
IS Thesis Abstract
Aging is considered a major risk factor for disease development in humans after age 28. We wanted to look at how the process of aging impacts the body on a cellular level and if we could ultimately manipulate the cell to prevent aging from occurring. We used a Boolean model designed specifically for studying the cellular network to determine the molecular consequences of having co-occurring growth signaling and DNA or mitochondrial damage. The model shows that cells have two forms of senescence, chromosomal and mitochondrial, and they respond to double-strand DNA damage by entering either, both, or undergoing apoptosis. Knocking out p16 eliminates chromosomal senescence and instead results in reversible G2 arrest, indicating a potential mechanism for the creation of immortal cells. Our model can generate testable hypotheses regarding the mechanism for inducing different senescence phenotypes. Understanding the connections between aging and cellular function will inform our strategies for combating diseases commonly associated with aging, as well as navigating the tradeoffs of cellular aging as a protective mechanism against cancer.
Figure 1. p16 knockout alters the cell’s response to gamma irradiation during the G2 phase of the cell cycle from a permanent arrest (senescence) to a temporary pause.