# Investigating Genes and Pathways Associated With Longevity and Neurodegenerative Disease

> **NIH NIH F31** · BAYLOR COLLEGE OF MEDICINE · 2022 · $46,752

## Abstract

Project Summary
Aging is the single largest risk factor in the development of neurodegenerative diseases. An interesting
characteristic of this link between aging and neurodegeneration is that populations predisposed to long lifespan
appear to be able to delay or avoid the development of neurodegenerative disease entirely. I hypothesize that
genes which modulate longevity can also confer neuroprotection, and that those genes protective against
neurodegenerative pathologies can also extend healthy brain function during the process of aging. In Aim 1, I
will identify which genes implicated in lifespan extension also ameliorate neurodegenerative disease
phenotypes. Utilizing a high-throughput robotic behavioral assay system in concert with the genetic tractability
of the Drosophila model, the Botas lab has compiled a neuroprotective gene dataset of over 1200 genes that
play protective roles in the neurons of Drosophila models of Alzheimer’s Disease, Parkinson’s Disease, and
Huntington’s Disease. I have also leveraged data from gene perturbation studies in numerous model organisms
documented in the literature to construct a network of evolutionarily-conserved lifespan extending genes. Human
longevity data will be integrated into this network using published genome-wide association and centenarian
variant data. I will overlay this network with data from our neuroprotective gene dataset to identify genes that
both extend lifespan and ameliorate neurodegenerative disease phenotypes. Then, gene set enrichment tools
will be used to characterize functional pathways in the network and to identify those related to neuroprotection.
Using genes within these pathways, and genes directly interacting with known neuroprotective variants, I will
then validate whether other longevity genes are neuroprotective in the context of disease. I will utilize Drosophila
models of neurodegenerative diseases to characterize whether alteration of these genes in neurons improves
disease-related phenotypes using a sensitive high-throughput neuronal performance assay system. In Aim 2, I
will identify whether genes that are protective in disease contexts can improve neuronal and/or glial
health during aging. First, I will utilize cross-sectional transcriptomic and proteomic time-series datasets from
the brains of flies, mice, and humans to characterize expression changes in the brain that occur with age and
disease conserved across evolution. Overlaying this data with our large database of neuroprotective genes, I
will identify changes in the brain that may play a protective role in preserving brain health or increase risk of
disease onset. I will then use our large-scale in vivo assay system to determine if manipulating the expression
of genes associated with aging or neuroprotection against disease improve the function of glia or a specific
neuronal subtype during aging. I will use pathway enrichment tools to determine potential mechanisms by which
genes that improve neuronal/gli...

## Key facts

- **NIH application ID:** 10534528
- **Project number:** 1F31AG079508-01
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** MEGAN MAIR
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $46,752
- **Award type:** 1
- **Project period:** 2022-08-03 → 2024-08-02

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10534528

## Citation

> US National Institutes of Health, RePORTER application 10534528, Investigating Genes and Pathways Associated With Longevity and Neurodegenerative Disease (1F31AG079508-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10534528. Licensed CC0.

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