The discovery of single gene mutations that extend lifespan in C. elegans formed the foundation of the idea that lifespan is not immutable but instead it is a tractable process that can be targeted therapeutically. As these first aging genes were systematically cloned, it became clear that many of them them encoded components of interacting endocrine signaling pathways whose primary role in C. elegans is to influence a developmental pathway called dauer formation. Worms enter the dauer larval stage under times of environmental stress (high population, high temperature and low food) and undergo a series of physiological changes that allow them to survive for extended periods of time without feeding or reproducing. When environmental conditions that support growth return, the worm can exit the dauer stage and develop into reproductive adults with no major adverse effects on their subsequent lifespan. While not all genes involved in dauer formation affect lifespan and not all genes involved in longevity affect dauer formation, the dauer formation process still provides a valuable system to investigate potential longevity pathways.
Many signaling pathways respond to small molecules whose identity cannot be inferred from genetics alone. Thus, in order to fully understand the function of these pathways, biochemical and chemical biology approaches must be utilized. My lab has used these approaches to identify candidate ligands for an orphan nuclear receptor as well as discovering an endocannabinoid signaling system in worms. The lab continues to be interested in identifying endogenous small molecules, as well as exogenous drug-like chemicals, that influence development and aging in the worm.