Epigenetic regulation of extreme longevity differences in ant castes

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.

Grant Number: 5R01AG055570-09
NIH Institute/Center: NIH
Principal Investigator: SHELLEY BERGER