Composition ofCaenorhabditis elegansextracellular vesicles suggests roles in metabolism, immunity, and aging

The nematodeCaenorhabditis eleganshas been instrumental in the identification of evolutionarily conserved mechanisms of aging.C. elegansalso has recently been found to have evolutionarily conserved extracellular vesicle (EV) signaling pathways. We have been developing tools that allow for the detailed study of EV biology inC. elegans. Here we apply our recently published method for high specificity purification of EVs fromC. elegansto carry out target-independent proteomic and RNA analysis of nematode EVs. We identify diverse coding and non-coding RNA and protein cargo types commonly found in human EVs. The EV cargo spectrum is distinct from whole worms, suggesting that protein and RNA cargos are actively recruited to EVs. Gene ontology analysis revealedC. elegansEVs are enriched for extracellular-associated and signaling proteins, and network analysis indicates enrichment for metabolic, immune, and basement membrane associated proteins. Tissue enrichment and gene expression analysis suggests the secreted EV proteins are likely to be derived from intestine, muscle, and excretory tissue. An unbiased comparison of the EV proteins with a large database ofC. elegansgenome-wide microarray data showed significant overlap with gene sets that are associated with aging and immunity. Taken together our data suggestC. eleganscould be a promising in vivo model for studying the genetics and physiology of EVs in a variety of contexts including aging, metabolism, and immune response.