ORCID
https://orcid.org/0000-0003-3770-5605
Date of Award
10-19-2023
Degree Name
Doctor of Philosophy (PhD)
Degree Type
Dissertation
Abstract
Aging is a time-dependent decline in organismal structure and function that ultimately results in death. Aging occurs in nearly all metazoan organisms, and is a major risk factor for many human diseases including cancer, diabetes, hypertension, heart disease, and Alzheimer’s Disease. The genetic pathways and mechanistic factors that underly the aging process are poorly understood. Control of aging in the nematode C. elegans can be accomplished via modulation of gene activity by genetic knockdown or by the introduction of inhibitory pharmaceutical compounds. While many such interventions have been described in the literature, understanding the underlying mechanisms that control aging remains a critical goal of aging research. Here, I advance the field by characterizing genetic and pharmacological mechanisms which control aging in C. elegans. Among these factors are phm-2 and eat-2, genes necessary for pharynx development and function that control aging via a unique interaction between dietary restriction and the innate immune system; the human amyloid beta peptide, the proposed causative agent of Alzheimer’s Disease, which enhances survival under pathogenic stress conditions; the ACE-inhibitor drug captopril and its mechanistic target acn-1, which control aging via interaction with the molting and developmental decision making pathways, and represent a highly conserved mechanism for lifespan extension across the animal kingdom; a novel allele of the well-studied daf-2 receptor tyrosine kinase gene that recapitulates human insulin receptoropathies; and osmotic stress response to sodium chloride concentration, which highlights a previously unrecognized role in nematode culture conditions that controls aging. These discoveries further our understanding of the mechanistic basis of aging in C. elegans.
Language
English (en)
Chair and Committee
Kerry Kornfeld
Recommended Citation
Egan, Brian McNally, "Genetic and Pharmacological Factors Control Aging in Caenorhabditis elegans." (2023). Arts & Sciences Electronic Theses and Dissertations. 3182.
https://openscholarship.wustl.edu/art_sci_etds/3182