Oleuropein Enhances Stress Resistance and Extends Lifespan via Insulin/IGF-1 and SKN-1/Nrf2 Signaling Pathway in Caenorhabditis elegans

Oleuropein (OLE) is a secoiridoid glycoside that mainly exists in olives with multifaceted health benefits. The present study aimed to investigate the stress resistance and lifespan extension effects of OLE in Caenorhabditis elegans. The results showed that OLE could significantly prolong the lifespan of C. elegans by 22.29%. Treatment with OLE also significantly increased the survival rates of worms against lethal heat shock and oxidative stress. Meanwhile, OLE supplementation increased the expression and activity of antioxidant enzymes and suppressed the generation of malondialdehyde in nematodes. In addition, the results from mutants implied that OLE might mediate longevity and stress resistance via DAF-16/FoxO, which played a vital role in the insulin/IGF-1 signaling (IIS) pathway. To further identify the molecular targets of OLE, mRNA level and loss-of-function mutants of IIS-associated genes were investigated. The data revealed that OLE activated IIS by down-regulating the upstream components, daf-2 and age-1. Furthermore, another stress response and longevity pathway in parallel to DAF-16, SKN-1/Nrf2, was also shown to involve in OLE-induced beneficial effects. Collectively, these results provide the theoretical basis that OLE could enhance the stress resistance and increase the lifespan of C. elegans through the IIS and SKN-1/Nrf2 signaling pathways.