Dendrobium nobile Lindl. Alkaloids promote longevity and stress resistance of Caenorhabditis elegans via DAF-16 and skn-1

OBJECTIVE: This study aimed to explore the anti-aging effects and mechanisms of Dendrobium nobile Lindl. Alkaloids (DNLA) on Caenorhabditis elegans (C. elegans). METHODS: The effects of DNLA on the lifespan of C. elegans under normal, oxidative stress and heat stress conditions were determined. Moreover, the deposition of lipofuscin in the intestinal tract, the mobility, pharyngeal pumping rate and SOD activity of C. elegans were assayed. The daf-16 mRNA expression levels of aging-related genes and nuclear localization of DAF-16 were tested. Furthermore, lifespan tests were conducted in CF1038[daf-16(mu86)] and EU1[skn-1(zu67)] mutant nematodes. RESULTS: The lifespan of C. elegans were prolonged after DNLA administration under normal conditions, oxidative stress and thermal stress, and the optimal concentration of DNLA was 0.35 μg/mL. In addition, DNLA significantly reduced lipofuscin deposition, enhanced mobility and increased SOD activity of C. elegans. The mRNA expression of daf-16, skn-1, sod-3, hsp-16.2 and ctl-1 were increased after 0.35 μg/mL DNLA treatment. DNLA also reduced cytoplasmic DAF-16 and increased its intermediate and nuclear distributions. The longevity promotion effect of DNLA on C. elegans disappeared after daf-16 or skn-1 mutation. After deletion of daf-16 or skn-1, the effects of DNLA on C. elegans were lost. CONCLUSIONS: DNLA can prolong the lifespan and stress resistance of C. elegans. The mechanism may be related to the up-regulation of daf-16 and skn-1, which further increases the activity of SOD.