Date of Award
Doctor of Philosophy
Genetics, Development and Cell Biology
Genetics and Genomics
The transcription factor FOXO is a known regulator of tissue homeostasis and animal lifespan. It was first identified in its ability to promote longevity through the insulin signaling pathway, and has since been implicated in numerous cellular processes. Members of the FOXO protein family control a wide array of cellular functions including metabolism, cell cycle arrest, apoptosis, stress resistance, and aging. In response to various signaling cues, FOXO proteins can localize into the nucleus and interact with DNA to regulate transcription. FOXO is known as a longevity gene, however, how FOXO behavior changes during aging is not well understood. Normal aging involves a progressive decline in cell function and an accumulation of oxidative damage. Additionally, with age comes a reduction in FOXO gene expression, and FOXO protein activity can become dysregulated. To resolve how FOXO activity changes with normal aging, we began with chromatin immunoprecipitation sequencing (ChIP-seq) to compare differences in FOXO chromatin binding between young and old organisms, using Drosophila melanogaster as a model. In Drosophila, there is only one homolog representing the FOXO protein family, known as dFOXO. Through our investigation, we found that the number of dFOXO-bound DNA regions decreases with age, and see a number of these targeted genes undergo changes in expression with aging. Some pathways targeted by FOXO at a young age are Hippo, WNT, and MAPK signaling pathways.
Birnbaum, Allison, "Analysis of transcription factor FOXO in the regulation of stress, aging, and neuromuscular tissue homeostasis in Drosophila melanogaster" (2020). Graduate Theses and Dissertations. 18098.
Available for download on Sunday, February 28, 2021