Mergan, Lucas, Menschaert, Gerben, Coussement, Louis, Braeckman, Bart P., Driesschaert, Brecht, Vandewyer, Elke, Temmerman, Liesbet, Dens, Elisabeth
[
International Worm Meeting,
2021]
Axenic dietary restriction (ADR) is the most potent form of dietary restriction in C. elegans known to date. Simply removing bacteria and growing worms in a sterile (semi-)defined culture medium results in more than doubling of lifespan, despite an abundance of calories and nutrients. The processes underlying this lifespan extension have remained enigmatic, as the mechanism seems distinct from other forms of DR and does not rely on known longevity pathways. One of the few molecular players that has been linked to ADR is CUP-4, a putative ligand-gated ion channel which when absent significantly reduces the longevity effect of ADR. CUP-4 is expressed solely in the coelomocytes, endocytic cells that have been suggested to serve scavenging, immune or hepatic functions. We wish to understand the underlying mechanisms of ADR longevity, and how the coelomocytes fit into this picture. We performed lifespan assays to determine the effect of coelomocyte ablation or disruption of endocytosis upon longevity under ADR. After optimizing a cell-specific RNA-sequencing set-up for adult C. elegans coelomocytes using fluorescence-activated cell sorting (FACS), we applied this pipeline to differentially analyze bulk coelomocyte transcriptomes under different dietary conditions and endocytic capacities. Our results revealed many differentially regulated immune genes, prompting us to investigate the potential involvement of diverse immune pathways (within the coelomocytes) in axenic dietary restriction. We hope that this will provide new insights into the lifespan-extending mechanisms of ADR, that can potentially be extrapolated to teach us more about the ageing processes at play in animals in general.