Effect of tRNA synthetase inhibitors on aging in Caenorhabditis elegans

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