# The effect of life span modifying interventions on Alzheimer's Disease in Drosophila and Mice.

> **NIH NIH R01** · BROWN UNIVERSITY · 2022 · $589,643

## Abstract

Project Summary/Abstract: (30 lines maximum)
 The overall goal of this proposal is to develop genetic and pharmacological interventions that will delay
the onset and progression of Alzheimer’s Disease (AD). AD and other Related Dementias (ADRD) affect well
over 5 million people in the United States. By mid-century, these numbers are predicted to at least triple. Despite
this, there are no effective treatments for these devastating illnesses. The onset and progression of AD has been
linked to age-related changes in several critical physiological pathways including cellular and mitochondrial
metabolism and genomic stability. We propose the age-related decline in the efficacy of these pathways
promotes AD-related neurodegeneration and interventions which improve and stabilize physiological pathways
leading to extension of healthy life span will delay the onset and progression of AD. In this proposal we will use
the fly and mouse AD models in combination to determine whether potential genetic and pharmacological
geroprotectors known to extend life span or health span in flies and mice, through an enhancement of the activity
of cellular and mitochondrial metabolism or improvement in genomic stability, delay the onset and progression
of neurodegeneration and other AD-related phenotypes in AD models in mice and flies. The goal of these studies
is to identify new and novel genetic and pharmacological geroprotectors that can be translated for use in the
treatment of AD.
 We will use specific molecular genetic and pharmacological interventions known to extend life span in
flies or to extend health span in mice in the context of molecular genetic models of fly and mouse AD. The effect
of each intervention will be evaluated in two different fly AD models (neuronal-specific expression of human Aß42
or human tau) and the 5XFAD mouse AD model.
 We will test the hypotheses that: (i) genetic interventions known to improve cellular and mitochondrial
metabolism or genomic stability and to extend life span in flies or health span in mammals serve as
geroprotectors that can delay the onset and progression of the neurodegeneration associated phenotypes in the
fly and mouse models of AD and (ii) pharmacological interventions known to improve cellular and mitochondrial
metabolism or genomic stability and extend life span in flies or health span in mammals can delay the onset and
progression of the neurodegeneration associated phenotypes in the fly and mouse AD models.
 We will determine whether these interventions delay the onset and progression of a series of AD-related
neurodegeneration phenotypes including: (i) decline in whole organismal health (life span in flies, frailty in mice);
(ii) loss of neurobehavioral robustness or resilience (mobility and circadian rhythms in flies, a series of
neurobehavioral tests in mice); (iii) microscopic histological examination of neurodegeneration in the brain and
the retina of flies and gross and microscopic neuro-pathological ex...

## Key facts

- **NIH application ID:** 10375432
- **Project number:** 5R01AG067306-03
- **Recipient organization:** BROWN UNIVERSITY
- **Principal Investigator:** STEPHEN L HELFAND
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $589,643
- **Award type:** 5
- **Project period:** 2020-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10375432

## Citation

> US National Institutes of Health, RePORTER application 10375432, The effect of life span modifying interventions on Alzheimer's Disease in Drosophila and Mice. (5R01AG067306-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10375432. Licensed CC0.

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