Date of Award

5-2016

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Legacy Department

Biological Sciences

Committee Member

Dr.Yuqing Dong, Committee Chair

Committee Member

Dr.Min Cao, Committee Co-Chair

Committee Member

Dr.William Baldwin

Committee Member

Dr.Charles Rice

Abstract

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 β-amyloid (Aβ)-toxicity induced body paralysis in C. elegans AD model. The genetic analysis indicated that the RJ/eRJ mediated Aβ 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 Aβ species. In considering that RJ/eRJ supplementation slowed down the Aβ-induced paralysis in C. elegans, it is possible that RJ/eRJ mediated protection against Aβ toxicity might be dependent on increasing the solubility of Aβ 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.

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