Studies of molecular mechanisms of royal jelly mediated healthspan promotion in Caenorhabditis elegans.

摘要

Numerous studies have demonstrated that many nutraceuticals have potential capacity to mitigate the symptoms of aging and age-related disorders. We found that Royal Jelly (RJ/eRJ) consumption could extend C. elegans lifespan and increase stress tolerance in an IIS/DAF-16 dependent manner. In consideration that the transactivity of DAF-16 is tightly controlled by its co-factors, our further results indicated that SIR-2.1, 14-3-3, and HCF-1 could interact with each other to fine-tune the activity of DAF-16. Additionally, these co-factors were also required in RJ/eRJ mediated stress tolerance.;Given that aging is characterized with progressively declined physiological functions, it is intriguing to investigate whether RJ/eRJ supplementation could slow down the development of neurodegenerative diseases. Strikingly, our results showed that RJ/eRJ supplementation delayed the beta-amyloid (Abeta)-toxicity induced body paralysis in C. elegans AD model. The genetic analysis indicated that the RJ/eRJ mediated Abeta toxicity alleviation required Insulin/IGF Signaling (IIS) pathway and DAF-16, rather than HSF-1 and SKN-1. Further research found that RJ/eRJ relied on DAF-16 to significantly improve the protein solubility in aged worms, which implied that RJ/eRJ supplementation promoted proteostasis and reduced proteotoxicity in AD worms. Additionally, RJ/eRJ also increased the solubility of Abeta species. In considering that RJ/eRJ supplementation slowed down the Abeta-induced paralysis in C. elegans, it is possible that RJ/eRJ mediated protection against Abeta toxicity might be dependent on increasing the solubility of Abeta species. Overall, our findings revealed that the anti-aging function of RJ/eRJ supplementation and underscored the relationship between the improved proteostasis and the prevention of neurodegenerative disorders.