Date of Award

Spring 5-3-2024

Level of Access Assigned by Author

Open-Access Thesis

Degree Name

Master of Science (MS)

Department

Biochemistry and Molecular Biology

Advisor

Aric Rogers

Second Committee Member

Robert Wheeler

Third Committee Member

Suzanne Angeli

Additional Committee Members

Dustin Updike

Lucy Liaw

Hannah Lust

Abstract

In the study of aging, there is a common paradigm that organisms allocate energy between surviving stressful conditions and growth/reproduction (Masoro, 2000). Driving mechanisms that favor the former extend lifespan and protect against cellular stress in different animal systems, including C. elegans. Dietary restriction is one such environmental stressor, which leads to downregulation of the energy-intensive process of mRNA translation (Karol, 2009; Tavernarakis, 2008). When knocked down in adulthood, IFG-1, a component of translation regulation, also protects against cellular stress. Protective effects of low translation appear to be orchestrated by certain tissues in C. elegans, namely neurons and the germline (Howard et al., 2021). Preliminary studies show that low IFG-1 in body muscle is not protective against protein unfolding stress in this tissue. Conversely, low translation in neurons or germline tissue upregulates structural and functional muscle genes and protects against muscle-specific proteotoxicity. To begin to determine if the upregulation of muscle genes is required for the protective effects of low translation, we screened for genes that inhibited the induction of muscle genes under low ifg-1. Recently, we have identified cbp-1, an RNA polymerase II transcription factor and histone acetyltransferase, as a component in the pathway between low neuronal translation (via ifg-1 RNA interference) and the upregulation of muscle genes. Here, we investigate the requirements for enhanced proteostasis conferred by low IFG-1, including the role of low CBP-1 and neuronal signaling.

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