Epigenetic regulation of extreme longevity differences in ant castes

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ABSTRACT Ants exhibit highly evolved eusocial behaviors including stark division of labor among female castes, where the queen carries out all reproduction and worker castes forage for food and defend the colony. Interestingly, and of great relevance to aging research, sterile workers are shorter-lived, with variable lifespans between distinct castes. Reproductive queens are long-lived, with lifespans differing three to ten-fold between queen and worker. Remarkably, the genomes of the sterile and reproductive castes are nearly identical, and thus differences in lifespan and behavior arise from non-genetic mechanisms. We investigate two species of ants, each with advantages for study of mechanisms linking aging with complex social behavior. In Harpegnathos saltator, loss or removal of the queen leads to altered behavior in the workers, with antennal dueling and eventual ascendance of workers to reproductive status. From a longevity perspective, the induced reproductive caste exhibits four-fold longer lifespan, thus providing a simple experimental switch to uncover important causality underlying aging. In Camponotus floridanus, there are two distinct worker castes, forager and soldier, with the soldier exhibiting a two-fold longer lifespan than the forager. These behaviors are programmed early in life, but exhibit plasticity during aging. Intriguingly, these castes can be experimentally reprogrammed from soldier-to-forager, thus providing a second paradigm to study the relationship of behavior to aging. Our overall premise is that genomic, epigenomic, and proteomic regulation—all hallmark foundational causes of aging—are at the heart of caste-differentiated lifespan disparities and relationship to caste behavior. We thus propose to utilize ants to investigate the epigenetic and physiological basis of the dramatic lifespan differences between reproductive and distinct worker castes. In H. saltator we have evidence in the long-lived reproductive caste for two mechanisms extending lifepan. First, we detect increased expression of a unique HSF (Heat Shock Factor) providing proteomic protection and longer lifespan via upregulation of the Heat Shock Response transcriptional pathway. Second, we find increased expression of a unique Ago2 (Arogonaut) that binds miRNAs that specifically target for destruction certain mRNAs that lower lifespan in short-lived workers. In C. floridanus we find that distinct chromatin-based epigenetic mechanisms are central to foraging, which is an age-linked behavior, and we can manipulate these pathways to reprogram soldier caste to forage. In the proposed research we will investigate these causal mechanisms, and then manipulate lifespan with a combination of genetic and epigenetic approaches to promote these mechanisms. The ant model system provides an exceptional opportunity to integrate social behavior with aging, and to uncover key epigenetic processes underlying universal aging pathways. Results from the research will provide fundamental knowledge about control of lifespan that can be translated to more sophisticated mammals.