Pyrroloquinoline quinone extends ' longevity through the insulin/IGF1 signaling pathway-mediated activation of autophagy.

Aging is the leading cause of human morbidity and death worldwide. Pyrroloquinoline quinone (PQQ) is a water-soluble vitamin-like compound that has strong anti-oxidant capacity. Beneficial effects of PQQ on lifespan have been discovered in the model organism (), yet the underlying mechanisms remain unclear. In the current study, we hypothesized that the longevity-extending effect of PQQ may be linked to autophagy and insulin/IGF1 signaling (IIS) in Our data demonstrate that PQQ at a concentration of 1 mM maximally extended the mean life of by 33.1%. PQQ increased locomotion and anti-stress ability, and reduced fat accumulation and reactive oxygen species (ROS) levels. There was no significant lifespan extension in PQQ-treated , , and mutants, suggesting that these IIS- and autophagy-related genes may mediate the anti-aging effects of the PQQ. Furthermore, PQQ raised mRNA expression and the nuclear localization of the pivotal transcription factor , and then activated its downstream targets , , and . Enhanced activity of the autophagy pathway was also observed in PQQ-fed , as evidenced by increased expression of the key autophagy genes including , and , and also by an increase in the GFP::LGG-1 puncta. Inactivation of the IIS pathway-related genes or by RNAi partially blocked the increase in autophagy activity caused by PQQ treatment, suggesting that autophagy may be regulated by IIS. This study demonstrates that anti-aging properties of PQQ, in the model, may be mediated the IIS pathway and autophagy.