Evaluation of Novel Mechanisms Mediating Innate Immunity of C. elegans in Response to Metformin

Abstract

The processes of aging and decline in the functioning of the immune system are strongly related, and the nematode Caenorhabditis elegans has been shown to be an appropriate model for the study of both. Caloric restriction is an intervention capable of modulating the activity of signaling pathways related to both the control of lifespan and the functioning of the immune system. A compound with an effect analogous to caloric restriction is metformin, a drug used to control type II diabetes and which has antimicrobial, immunomodulatory and longevity-increasing properties in animal models. In C. elegans, for metformin to be able to extend lifespan, it needs to act on live bacteria that the worm feeds on. Recognition of bacteria in the gut of C. elegans may require double-stranded RNA transporters expressed in this region, mainly the SID-2 protein. C. elegans with increased longevity on caloric restriction and treatment with metformin showed upregulation of the expression of genes related to the immune system, including sodh-1. Thus, this project seeks to understand whether the effect of increased lifespan promoted by metformin is dependent on the activity of an immune system's gene of C. elegans and/or the ability to recognize bacterial RNAs from food.