6-PPD quinone at environmentally relevant concentrations induces immunosenescenece by causing immunosuppression during the aging process

Abstract

6-PPD quinone (6-PPDQ) could accelerate aging process. However, the underlying mechanism for the acceleration in aging process remains largely unclear. We aimed to examine the role of immunosuppression in 6-PPDQ in causing accelerated aging process in Caenorhabditis elegans. 6-PPDQ (0.1–10 μg/L) could decrease locomotion and increase reactive oxygen species (ROS) generation at both adult day-8 and day-12. 6-PPDQ at adult day-12 induced more severe immunosuppression reflected by decrease in expression of antimicrobial genes (lys-1, lys-7, spp-1, and dod-6) compared to that at adult day-8. Meanwhile, 6-PPDQ (10 μg/L) affected expressions of some transcriptional factor genes during the aging. Among them, at adult day-8, susceptibility to 6-PPDQ toxicity was caused by RNAi of daf-16, bar-1, elt-2, atf-7, skn-1, and nhr-8, and resistance to 6-PPDQ toxicity was induced by RNAi of daf-5, daf-3, and daf-12. Additionally, RNAi of daf-16, bar-1, elt-2, atf-7, skn-1, and nhr-8 caused more severe decrease in lys-1 and lys-7 expressions in 6-PPDQ exposed nematodes, whereas decrease in lys-1 and lys-7 expressions in 6-PPDQ exposed nematodes was inhibited by RNAi of daf-5, daf-3, and daf-12. The 6-PPDQ toxicity and 6-PPDQ induced decrease in lys-1 and lys-7 expressions were further suppressed by RNAi of insulin ligand genes (ins-6, ins-7, and daf-28) and receptor gene daf-2. Therefore, immunosuppression-caused immunosenescenece mediated the acceleration in aging process in 6-PPDQ exposed nematodes, which was under the control of certain transcriptional factors.