Investigating Central Target Genes of Life-Extending Drugs in Caenorhabditis elegans
Aging is regulated by both genetic and environmental factors, but the mechanisms underlying lifespan extension remain poorly understood. In this project we focused on lifespan-extending drugs (NLEs) in C. elegans and identified 130 such compounds from previous literature, analyzing their gene-drug interactions using the MOSAIC database. Our goal was to validate predicted hub genes and assess their roles in lifespan regulation through RNAi treatments in N2 wild-type worms. The top gene identified by the MOSAIC database, T13F2.2, was selected for RNAi experiments, where worms were treated with RNAi constructs targeting T13F2.2, and lifespan was monitored. Control groups were treated with RNAi targeting L4440.
Kaplan-Meier survival analysis revealed a significant lifespan extension in the T13F2.2 RNAi-treated group compared to the control (p < 0.001). Contrary to our hypothesis, which predicted a lifespan reduction due to T13F2.2 knockdown, the results suggest that T13F2.2 plays an unexpected role in regulating longevity. Experimental considerations, such as potential damage to worms during scoring, may have affected the results, but the observed extension in lifespan is likely a true biological effect of T13F2.2 knockdown. To further validate our findings, additional hub genes should be tested using RNAi or knockout strains. Further investigation into the molecular mechanisms by which compounds modulate genetic pathways to extend lifespan is needed.