Paecilomyces variotii extract increases lifespan and protects against oxidative stress in Caenorhabditis elegans through SKN-1, but not DAF-16

A natural extract from Paecilomyces variotii (P. variotii extract, PVE), an endophytic fungus, has been used widely to improve agricultural crop performance and control multiple plant pathogens. Most recent studies focused on its application as a plant growth promoter, while relatively few studies have been reported on the antioxidant potential in vivo and the underlying mechanism. The present study was designed to determine the antioxidant activities of PVE and its mechanisms using Caenorhabditis elegans. Results showed that, compared to the solvent control, PVE at 1.0, 10 and 100 ng/mL significantly extended the lifespan of C. elegans by 36.60%, 59.80% and 53.30%, respectively. PVE at 10 ng/mL consistently promoted nematodes growth, but all treatments did not influence nematode fecundity, locomotion behavior, and pharyngeal pumping. Furthermore, PVE at the three tested concentrations significantly reduced accumulation of reactive oxygen species (ROS), lipofuscin, lipid and malondialdehyde (MDA) content, meanwhile significantly promoted activities of superoxide dismutase (SOD), catalase (CAT) and glutathione S-transferase (GST) in the nematodes. Compared with the solvent control, PVE up-regulated gene expression of skn-1, mev-1, sod-3, and daf-2, but significantly down-regulated the expression of nhr-49 and daf-16. Further evidence revealed that PVE at the three concentrations significantly promoted nuclear localization of SKN-1, but not affected that of DAF-16, indicating the complex roles of DAF-16 and SKN-1 in stress resistance and longevity regulation. Overall, our results demonstrated that SKN-1 played a critical role in increasing lifespan of C. elegans and protecting the nematodes from oxidative stress, independent of DAF-16.