# Aging and rejuvenation: An ant model to study the regulation of longevity

> **NIH NIH R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2022 · $637,258

## Abstract

Project summary:
Ants are social insects that can be developed as experimentally tractable organisms for probing the dynamic
changes in the epigenetic programs that control an array of processes, including aging. Aging is a process of
progressive decline in intrinsic physiological functions. There is a well-established trade-off between lifespan
and reproduction as higher reproductive activity in females is associated with shorter lifespan. However, in
social insects, the reproductive queen has up to 10X longer lifespan than non-reproductive workers. In the ant
Harpegnathos saltator, adult individuals that are not exposed to queen pheromones can undergo a reversible
switch from non-reproductive workers to reproductive pseudo-queens (gamergates) that exhibit fully developed
ovary and, importantly, a 5X increase in lifespan, showing that aging is reversible. Lifespan is shortened again
when gamergates are reverted to workers (revertants). Thus, Harpegnathos provides an effective system to
study epigenetic regulation of aging and rejuvenation given the adult plasticity that allows switching between
castes.
We have performed transcriptome analysis of the longevity-regulatory tissues: the fat body, ovary and brain, in
workers vs. gamergates vs. revertants. We have identified a group of differentially expressed genes (DEGs),
some of which have been implicated in the regulation of longevity, e.g. IIS (insulin and IGF signaling) pathway
components. To further analyze the genetic and epigenetic regulation of longevity in ants, we will first compare
physiology, lifespan, transcriptome and histone modifications in gamergates derived from young vs. old
workers to ascertain the epigenetic regulation of aging and, most intriguingly, rejuvenation. The cellular
localization and functions of important DEGs will be further analyzed. Second, we will utilize our newly
established genetic tool – CRISPR in ants – to generate knockout (KO) ants in the two DEGs in the ovary, Hs-
IMPL2 and Hs-ALS, which likely act as inhibitors of IIS in ants. These KO ants will be used to characterize the
role of IIS in the dramatically extended lifespan in gamergates. Third, Hs-ILP1 (insulin-like peptide 1) is
differentially expressed in the brain and Hs-ILP2 in the ovary. While both Hs-ILP1 and Hs-ILP2 are strongly
increased in gamergates compared to workers, IIS is decreased in the fat body and ovary. To address this
paradox, we will analyze (a) the role of Hs-ILP1 and -ILP2 in regulating the two branches of IIS: AKT and
MAPK; (b) the role of Hs-ImpL2 and Hs-ALS in regulating activity of Hs-ILPs; and (c) how two insulin receptors
(InRs) mediate the role of Hs-ILPs in differentially regulating IIS.

## Key facts

- **NIH application ID:** 10425261
- **Project number:** 5R01AG058762-05
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Claude Desplan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $637,258
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10425261

## Citation

> US National Institutes of Health, RePORTER application 10425261, Aging and rejuvenation: An ant model to study the regulation of longevity (5R01AG058762-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10425261. Licensed CC0.

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