Graduation Year
2025
Document Type
Master's Thesis
Degree
Master of Science
Program
Biological Science
Partner Organization
Buck Institute for Research on Aging
Program Director
Patti Culross, MD, MPH
First Reader
Pankaj Kapahi, PhD
Second Reader
Tyler Hilsabeck
Abstract
In this study, we used the model Drosophila melanogaster to investigate mechanisms of aging variance by modulating neural expression of the developmental HOX gene Abdominal-B (Abd-B). We hypothesized that neural expression of Abd-B is sufficient to drive aging and that Abd-B shortens lifespan through its role as a transcription factor, modulating expression of other interactor genes. Our lab conducted a Drosophila Genome-Wide Association Study (GWAS) targeting aging regulators, which indicated Abd-B to be a candidate for regulating aging variance. We tested this association using a dietary restriction (DR) diet to model Abd-B expression, as DR has been established as a robust method of lifespan extension. The lifespan effects we observed from Abd-B modulation on DR flies indicated Abd-B’s role in aging variance— the suppression of a proven lifespan-extension method from the overexpression of a lifespan-shortening gene illustrated that Abd-B's overexpression drives aging. Our lab has seen changes in Abd-B transcription with age, particularly in neurons, so this study assessed the tissue specificity of Abd-B expression and determined that neural expression was sufficient to modulate aging variance. Modulating Abd-B expression in the brain was then shown to influence lifespan variance and health. Through RNA sequencing, we determined Abd-B to enact these aging effects through upregulation of the mTOR pathway, a known aging driver.
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