# Calorie Restriction and Hallmarks of Aging in Drosophila

> **NIH NIH R56** · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · 2023 · $415,209

## 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. Aging has
been linked with an array of conserved cellular processes and molecular pathways marked as hallmarks.
However, relationship between the hallmarks has not been clearly defined. Determination of the interaction
among hallmarks would open more realistic opportunity for identification of novel therapeutic targets to
decelerate organismal aging. We will determine trajectories and relationships between two hallmarks of aging –
deregulated nutrient sensing and mitochondrial dysfunction – by using our model of accelerated or decelerated
aging.
Calorie restriction (CR) delays the onset of age-related changes, decreases the rate of aging, and extends the
life span in a variety of species. Our preliminary data show that shifting flies from a high-calorie to a low-calorie
diet immediately decreases fly mortality, affects metabolism, and extends survivorship. In contrast, shifting from
a low diet to a high diet accelerates aging. Dynamic metabolic adaptations to available nutrients are reflected in
the tissue-specific transcriptome, which provides an excellent model to uncover rapid changes in the hallmarks
of aging to start dissecting their relationship. Our project is designed to determine interactions between nutrient
sensing and mitochondrial function in flies, in which the rate of aging is reduced or accelerated by shifting flies
to different diets. We will use an integrated experimental and genetic approach that includes analysis of changes
in metabolism, transcriptome, metabolome, mitochondrial function, and physiological markers of fly health.
 We propose the following specific aims: Determine effects of rapid change in aging rate on deregulated
nutrient sensing by using an integrated approach involving the study of metabolism, and determination of the
transcriptomic and targeted metabolomics profile in different tissues of shifted flies (Aim 1). Determine effects of
change in the aging rate on mitochondrial dysfunction (Aim 2). Determine interactions between the two hallmarks
by using our model of accelerated and decelerated aging by performing epistatic analysis (Aim 3). Our proposed
study will advance our basic knowledge on the molecular and physiological mechanisms underlying interactions
among hallmarks of aging and determine how their hierarchy affects organismal aging. Hallmarks of aging are
highly conserved across species, suggesting that our findings could be translated to mammalian organisms.

## Key facts

- **NIH application ID:** 10901041
- **Project number:** 1R56AG082788-01
- **Recipient organization:** UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
- **Principal Investigator:** BLANKA ROGINA
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $415,209
- **Award type:** 1
- **Project period:** 2023-09-15 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10901041

## Citation

> US National Institutes of Health, RePORTER application 10901041, Calorie Restriction and Hallmarks of Aging in Drosophila (1R56AG082788-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10901041. Licensed CC0.

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