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Honey bees are exposed to an array of potentially toxic chemicals, which differ in aspects of their toxicity as well as their fate in the environment. In Chapter 1 of my thesis, I discuss the exposure and effects of toxic chemicals to honey bees through the lens of chemical kinetics. I also describe applications of kinetic modeling for the development of mechanistic models of colony exposure. In chapter 2, I demonstrate how kinetic modeling (toxicokinetic-toxicodynamic modeling) can be used to predict the long-term effects of chemical exposure on the survival of individual honey bees and the growth of their colonies. I focus on metal pollutants (As, Cd, Li, Pb, and Zn), which honey bees are exposed to in a range of human modified environments. I found that a toxicokinetic-toxicodynamic model (the General Unified Thresholds Model of Survival, GUTS) better predicted the survival of honey bees in the lab than a simple extrapolation of a standard (probit) model that is commonly used in honey bee risk assessments. When predicting the effects of metal exposure on colony growth, differences between modeling approaches were highly case-specific. In chapter 3, I focus on the exposure and effects of metals to immature honey bees. Specifically, I describe an experiment using queen-rearing boxes to measure the accumulation of metals into larval food (nurse jelly) and developing queen larvae. I also describe a laboratory study on the toxicity of different metals to honey bee larvae reared in vitro. I found that Cd and Li translocate into larval foods at a higher rate than has been observed for pesticides. Furthermore, when applied to the larval diet in vitro, As, Li, and Zn affected the survival of honey bee larvae at field-relevant concentrations.

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.