# Molecular mechanisms underlying the preservation of neural stem cell quiescence during aging

> **NIH NIH RF1** · BROWN UNIVERSITY · 2022 · $350,591

## Abstract

PROJECT SUMMARY
Cognitive decline is a major feature of aging and neurodegenerative diseases such as Alzheimer’s disease.
Neurogenesis, the formation of new neurons, supports learning, memory, mood regulation, and sensory
functions in the healthy mammalian brain. During aging, neurogenesis is dramatically reduced due to
impairments in neural stem cell (NSC) pools. The mechanisms responsible for dysfunction of the NSC
reservoir are not fully understood, but significant evidence implicates changes to the quiescent NSCs, which
are the source of the neurogenic lineage. Ths work investigates the mechanisms responsible for failed
activation of quiescent NSCs with age. This project is significant because identification of the mechanisms
underlying dysfunction of quiescent NSCs with age will reveal strategies to restore new neuron formation in
aging and neurodegeneration. Published and preliminary work shows that quiescent NSCs, though relatively
dormant, are defective at the chromatin, gene expression, and metabolic levels with age. This study takes an
integrated approach to reveal the specific target genes and processes responsible for defects in NSC
quiescence with age. Specific Aim 1 will investigate how mitophagy regulates metabolic health of NSCs during
aging. Aim 2 employs an integrated multi-omics strategy to fully elucidate the epigenomic and metabolic
changes that occur the neurogenic lineage with age. Finally, Aim 3 will address the mechanisms by which
NSCs return to quiescence, and the extent to which failure in this process results in depletion of the functional
NSC pool with age. Collectively, this work will result in a comprehensive understanding of how dormant NSCs
are affected by aging in the mammalian brain. In the long term, these studies have the potential to lead to the
development of interventions to improve healthy aging and restore cognition in the context of
neurodegeneration.

## Key facts

- **NIH application ID:** 10522209
- **Project number:** 2RF1AG053268-06
- **Recipient organization:** BROWN UNIVERSITY
- **Principal Investigator:** Ashley E Webb
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $350,591
- **Award type:** 2
- **Project period:** 2017-09-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10522209

## Citation

> US National Institutes of Health, RePORTER application 10522209, Molecular mechanisms underlying the preservation of neural stem cell quiescence during aging (2RF1AG053268-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10522209. Licensed CC0.

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