6-PPD quinone induces lifespan reduction by causing immunosuppression via DAF-16/PMK-1 signaling in Caenorhabditis elegans

In Caenorhabditis elegans , suppression in innate immunity could be induced by 6-PPD quinone (6-PPDQ); however, underlying mechanism remains unknown. RNA interference (RNAi) of antimicrobial genes ( lys-7 and spp-1 ) enhanced 6-PPDQ-induced lifespan reduction and increased 6-PPDQ accumulation. Accompanied with these, expressions of daf-16 encoding FOXO transcriptional factor and pmk-1 encoding p38 MAPK were decreased by 6-PPDQ exposure. In 6-PPDQ exposed nematodes, daf-16 and pmk-1 RNAi caused more severe inhibition in expression of antimicrobial genes. Additionally, 6-PPDQ caused lifespan reduction and 6-PPDQ accumulation were accelerated by daf-16 and pmk-1 RNAi. 6-PPDQ induced decrease in expression of antimicrobial genes and lifespan reduction and 6-PPDQ accumulation could be suppressed by pharmacological treatment with cuminaldehyde. Moreover, these beneficial effects of cuminaldehyde treatment were inhibited by daf-16 and pmk-1 RNAi, which further suggests crucial functions of DAF-16 and PMK-1. Our results highlight association of immunosuppression with 6-PPDQ-induced lifespan reduction, which was controlled by molecular signals of DAF-16 and PMK-1. • lys-7 and spp-1 RNAi enhanced 6-PPDQ induced lifespan reduction and 6-PPDQ accumulation. • 6-PPDQ induced immunosuppression was strengthened by RNAi of daf-16 and pmk-1. • daf-16 and pmk-1 RNAi accelerated 6-PPDQ caused lifespan reduction and 6-PPDQ accumulation. • Beneficial effect of cuminaldehyde against 6-PPDQ toxicity was inhibited by daf-16 and pmk-1 RNAi.