# Epigenetic regulation of extreme longevity differences in ant castes

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $389,410

## Abstract

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, the sterile workers are short-lived, while the reproductive queens are
long-lived, with lifespans differing three to ten-fold between queen and worker. Remarkably, the genomes of
these sterile and reproductive castes are nearly identical, and thus differences in lifespan (LS) and behavior
likely result from epigenetic regulation. Furthermore, in the species Harpegnathos saltator, loss or removal of
the queen leads to altered behavior in the workers, with antennal dueling and eventual ascendance of typically
one or two workers into reproductive “gamergate”, or pseudo-queen. From a longevity perspective, the
gamergate exhibits longer LS and thus it appears that both behavior and lifespan are epigenetically determined
during this switch. In addition, older workers reprogram much less efficiently into reproductive gamergate
status. Our overall premise is that epigenetic regulation is at the heart of this caste-differentiated life span
disparity, and that once we understand the basis of the epigenetic regulation, we can manipulate lifespan with
epigenetic therapeutics and genetics in this relatively simple but socially complex organism. These results will
provide fundamental knowledge that can be investigated in more sophisticated mammals.
 We propose to utilize H. saltator ants to investigate the epigenetic and physiological basis of the
dramatic LS differences between reproductive and worker castes. We will carry out transcriptomic, proteomic,
and epigenomic profiling of workers and queens of the same chronological age, and of young and old queens,
to explore the basis of the plasticity in lifespan. We hypothesize that both known and novel mechanisms are
lengthening LS in queens, which show such dramatic difference from worker LS. In addition, we will uncover
the basis of the inefficient reprogramming of older workers into reproductive gamergates. Our recent published
evidence (Science, 2016) supports the view that behavioral plasticity in ants is enhanced by epigenetic
mechanisms during young adulthood, and that this plasticity is lost with age; however, the molecular
mechanisms underlying this phenomenon remain unknown. Our preliminary data regarding chromatin marking
show that regulatory loci near to active genes in gamergate queens bear activating histone H3K27 acetylation
and these same loci in worker are marked with repressive H3K27 methylation. Intriguingly, these repressed
loci in worker ants appear to be “poised” for activation with H4K16 acetylation. We hypothesize that in young
workers key loci are epigenetically poised to become activated and this poising becomes degraded as workers
age, leading to inefficient reprogramming to reproductive status. In the proposed research ...

## Key facts

- **NIH application ID:** 9952287
- **Project number:** 5R01AG055570-04
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** SHELLEY L BERGER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $389,410
- **Award type:** 5
- **Project period:** 2017-09-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9952287

## Citation

> US National Institutes of Health, RePORTER application 9952287, Epigenetic regulation of extreme longevity differences in ant castes (5R01AG055570-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9952287. Licensed CC0.

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