Genetic Analysis of Stress Response and Life Span Regulation in Caenorhabditis Nematodes

Abstract

This thesis investigates the roles of the Axin homolog PRY-1 and the Insulin/IGF-1 signaling (IIS) pathways in Caenorhabditis nematodes to elucidate their influence on aging, stress responses, and metabolic regulation. Comparative analyses between C. elegans and C. briggsae highlight conserved and divergent genetic mechanisms within the IIS pathway that regulate lifespan and metabolic processes. Transcriptome profiling reveals novel genes downstream of the daf-2-daf-16 pathway, furthering our understanding of the underlying genetic networks. PRY-1, a key component of the Wnt signaling pathway, plays a significant role in regulating axis formation, lipid metabolism, neuron and vulva development, cell polarity, and lifespan. This research examines PRY-1’s interactions with BAR-1 (a β-catenin homolog), and how these interactions influence lipid metabolism, vitellogenin expression, lifespan, and vulva development. This work extends our understanding of the IIS and Wnt pathways, emphasizing these signaling axes' evolutionary importance in aging, metabolic regulation, and stress response.