Biomedical Sciences ETDs

Publication Date

Summer 7-29-2025

Abstract

Aging is a multifaceted biological process characterized by the progressive decline in physiological integrity, ultimately leading to impaired function and increased vulnerability to disease. One emerging aging intervention involves the modulation of the Integrated Stress Response (ISR) via the transcription factor ATF-4, a conserved regulator of longevity across species. This dissertation investigates the effects of tRNA synthetase inhibitors- compounds that activate ATF-4 signaling- on lifespan and healthspan in Caenorhabditis elegans. I hypothesize that tRNA synthetase inhibition will lead to increased lifespan, healthspan, and autophagy in C. elegans in an atf-4-dependent manner. This work supports a conserved mechanism of longevity via translational control of ATF-4 and highlights tRNA synthetase inhibitors as a promising new class of geroprotective compounds.

Keywords

aging, C. elegans, ATF-4, gcn4, ATF4, lifespan

Document Type

Dissertation

Language

English

Degree Name

Biomedical Sciences

Level of Degree

Doctoral

Department Name

Biomedical Sciences Graduate Program

First Committee Member (Chair)

Laura Gonzalez Bosc

Second Committee Member

Mark McCormick

Third Committee Member

Amy Gardiner

Fourth Committee Member

William Curt Hines

Fifth Committee Member

Alexander Mendenhall

Available for download on Thursday, July 29, 2027

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