# Non-Autonomous control of aging in Drosophila

> **NIH NIH R01** · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · 2021 · $410,000

## Abstract

Project Summary:
 Aging is associated with functional decline in metabolic, physiological, proliferative, and tissue
homeostasis leading to deterioration on the organismal level. The identification of therapeutic strategies that
prevent or postpone age-related decline has become an urgent goal of biomedical science research. A key
issue is the identification of tissue(s) that can drive organismal ageing. We will test a model of tissue-specific
metabolic, physiological and molecular changes that drive organismal aging non-autonomously.
Indy (I'm not dead yet) encodes a plasma membrane citrate transporter predominantly expressed in fly
metabolic tissues: the midgut, fat body and oenocytes (fly liver). We have shown that organism-wide reduction
in Indy activity extends fly health and longevity by altering energy metabolism. Indy flies have decreased lipid
and glucose levels, increased insulin sensitivity, increased mitochondrial biogenesis and reduced oxidative
damage, among other effects. Additionally, we have shown that down-regulation of Indy expression preserves
intestinal stem cell homeostasis, suggesting an important link between metabolic changes in the midgut,
physiological homeostasis and organismal aging. Moreover, we have obtained preliminary data that specific
Indy reduction in fly midgut mimics many beneficial effects of Indy reduction found in whole body Indy
hypomorphs including longer lifespan. Therefore, our working hypothesis is that INDY reduction in the midgut
regulates citrate levels leading to metabolic changes that preserve tissue homeostasis and slows aging non-
autonomously. We propose the following specific aims. Confirm that the midgut has a key role in longevity
regulation by comparing the effects on fly health and lifespan when INDY is reduced solely in the midgut, the
fat body, or the oenocytes (Aim 1). Determine effects and mechanism of Indy reduction by using an integrated
approach involving study of metabolism, and determination of the transcriptomic and targeted metabolomics
profile in Indy flies (Aim 2). Determine the physiological mechanism by which Indy reduction in the midgut
slows aging on organismal level (Aim 3). Our proposed study will advance our basic knowledge on the
molecular and physiological mechanisms underlying non-autonomous effects on organismal aging. Reducing
INDY homologs in worms, mice, rats and non-human primates leads to similar metabolic outcome, suggesting
that our findings could be translated to mammalian organisms.

## Key facts

- **NIH application ID:** 10177832
- **Project number:** 5R01AG059586-04
- **Recipient organization:** UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
- **Principal Investigator:** BLANKA ROGINA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $410,000
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10177832

## Citation

> US National Institutes of Health, RePORTER application 10177832, Non-Autonomous control of aging in Drosophila (5R01AG059586-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10177832. Licensed CC0.

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