# Social control of lifespan regulation via glial plasticity in ants

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2021 · $332,869

## Abstract

ABSTRACT
Age-related neurodegenerative diseases pose an immense biomedical challenge. Plastic changes in the brain
underpin aging-related cognitive decline and neurodegeneration but little is known about the neuroprotective
pathways that forestall these processes in healthy aging brains. In mammals, glia composition and
properties display age-related dynamics including a shift to a more neuroprotective function as the brain
ages. In Drosophila, glia are also implicated in regulating brain health and lifespan, underscoring a deep
evolutionary conservation of glia function.
The goal of this proposal is to determine how glia contribute to healthy brain aging and longevity using
Harpegnathos saltator ants, a powerful model system to study the molecular and epigenetic regulation of
aging. Adult Harpegnathos workers can become queens (called “gamergates”) via a phenotypic transition
that results in a 5-fold extension of lifespan.
We performed single-cell RNA-seq before and after the transition of workers to long-lived gamergates and
found remarkable plasticity in the glia. Specifically, we found that ensheathing glia cells were substantially
expanded in gamergate brains. Interestingly, gamergates retained high levels of ensheathing glia as they
aged, whereas worker brains were rapidly depleted of these cells over the course of their life.
Ensheathing glia cells respond to damage and provide general housekeeping and neuroprotective functions in
Drosophila but they are not known to contribute to healthy brain aging and longevity. Our data suggest the
hypothesis that an expanded ensheathing glia compartment contributes to the prolonged lifespan of
gamergates.
In Aim 1, we will determine the molecular and cellular changes that accompany the ensheathing glia
dynamics during differential aging in worker and gamergates. In Aim 2, we will investigate the role of a specific
receptor that is expressed in ensheathing glia cells and might directly regulate their expansion in response to
the expression of a reproductive gene in gamergates. In Aim 3, we will utilize primary ant neuronal cultures and
genetic manipulations in Drosophila to determine the causal link between ensheathing glia and longevity and
its mechanism.
Together, our work will elucidate 1) new molecular pathways that control glia plasticity, 2) a new biological role
for glia plasticity, and 3) mechanisms for the regulation of healthy brain aging by glia.

## Key facts

- **NIH application ID:** 10197364
- **Project number:** 1R01AG071818-01
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Roberto Bonasio
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $332,869
- **Award type:** 1
- **Project period:** 2021-04-15 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10197364

## Citation

> US National Institutes of Health, RePORTER application 10197364, Social control of lifespan regulation via glial plasticity in ants (1R01AG071818-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10197364. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*