Project Summary/Abstract Eusocial insects like ants have emerged as excellent models for the study of epigenetic regulation and lifespan due to their unique behavioral and morphological plasticity in response to social stimuli. Individual workers in an ant colony have nearly identical genomes but exhibit striking differences in behavior and lifespan. The outstanding and still relatively unexplored question remains: “How does the social environment alter the epigenetic state of mature, full-developed organisms with respect to behavior and aging?” Research in this field has been limited by the lack of suitable eusocial model systems that exhibit (A) complex social structures, and (B) can be utilized to ask questions about social state. Our preliminary data show that socially isolated ants exhibit drastically reduced lifespan. However, pairing a socially isolated ant with a 3D-printed ant model, coated with all the cuticular hydrocarbons of the individual’s original colony, rescues the lifespan decrease induced by isolation. I also observe drastic morphological changes in overall brain size in addition to distinct brain structures, as a function of social setting. I have also developed a behavioral assay that shows increased lethargy during social isolation. I performed RNA-sequencing to identify Obp56e has reduced expression during isolation, but elevated expression in the rescue. Obp56e is an odorant binding gene critical in synthesizing cuticular hydrocarbons. I will reveal how an odorant binding gene regulates lifespan differences, leads to region-specific brain atrophy, and controls behavioral changes. I will use my findings to modulate the expression of odorant binding protein(s) in the brain of C. floridanus to regulate lifespan and understand behavioral changes as a function of social isolation. I hypothesize that Obp56e will be critical in modulating the longevity of socially isolated individuals. The goal of this proposal is to reveal how the social environment influences lifespan and behavior in the ant species Camponotus floridanus. In Aim 1, I will elucidate the effect of social environment on C. floridanus by generating a brain specific overexpression of Obp56e in isolated individuals in order to end their lifespan, using behavior as a secondary output. In Aim 2, I will determine the cuticular hydrocarbon(s) (CHCs) that regulate lifespan difference as a function of social setting in C. floridanus. To integrate the aims, I will perform RNA-sequencing on the brains of ants who received the compound that provides rescue and compare to the total CHC rescue. These studies are likely to be highly applicable to human health by the functional investigation of conserved candidate genetic targets for lifespan modulation. I am in a unique position to establish the fundamental groundwork of social influence on lifespan and behavior before long-term effects of social distancing become a public health emergency.