Metabolism of Dietary Polyunsaturated Fatty Acids Modulates Healthspan of C. elegans

Abstract

Dietary omega-3 and omega-6 unsaturated fatty acids (UFAs) are essential for normal man physiological processes in multiple organisms. However, their mechanism(s) that drive these processes remain largely unknown. Recent studies showed that downstream metabolites of UFAs play a critical role in inflammation, blood pressure regulation, pain perception, carcinogenesis, wound healing, and tissue and neural repair. Here, we hypothesize that the metabolites of dietary UFAs affect both development and aging. To study the role and underlying mechanism of the effect of UFA metabolites on the healthspan of organisms, we used C. elegans as a model organism because 1) C. elegans has been wildly used for aging study; 2) The C. elegans genome is highly conserved; 3) genetic modifications are relatively easy; 4) vast community resources are available for minimum cost or free and 5) genetic tools are largely available. As a result, this model organism greatly facilitates the mechanistic investigation of the effects of UFA metabolites. In this specific presentation, we will present metabolomic data obtained from the state-of-the-art ultra-performance liquid chromatography coupled with tandem mass spectrometry to demonstrate that C. elegans produces similar classes of UFA metabolites comparable to humans and mammals, and the endogenous levels of cytochrome P450 (CYP) metabolites of UFA change with the age of C. elegans. We will also present the effect of treatment with CYP UFA metabolites or modulation of UFA CYP metabolism on aging (lifespan and thrashing assay), reproduction (egg laying and egg viability assay) and neurodevelopment (fluorescent imaging). In conclusion, our results indicate that UFA metabolites play important physiological roles in C. elegans, and future mechanistic studies will also be discussed.