# Mechanisms underlying a decline in neural stem cell migration during aging

> **NIH NIH F30** · STANFORD UNIVERSITY · 2023 · $40,168

## Abstract

PROJECT SUMMARY
Aging is the main risk factor for a variety of brain diseases, such as stroke and neurodegenerative diseases.
Additionally, recovery from stroke and other types of brain injury declines with age. There is an unmet need for
the development of more effective therapies centered on aging to counter the decline in repair capacity and the
onset of neurodegenerative diseases. The adult brain contains neurogenic stem cell niches that have the
potential to generate new progeny that migrate to distal sites, which could play a critical role for repair in age-
related disease and injury. During aging, neural stem cells show a progressive loss in their ability to proliferate
and give rise to new neurons (neurogenesis), and this is accompanied with a decline in repair ability. However,
the mechanisms underlying this deficit are not well understood. My preliminary findings suggest that aging
leads to changes in cell migration and adhesion abilities in neural stem cells, with activated neural stem cells
and their progeny becoming less migratory with age. Based on these findings, my specific hypothesis is that
with age, activated neural stem cells undergo reversible changes in cell migration and adhesion that lead to
decreased neurogenesis. My proposal aims to elucidate the mechanisms underlying the age-related decline in
migration in activated neural stem cells and uncover therapeutic strategies to mitigate this.
Aim 1 will identify specific genes and regulatory factors that underlie the migratory defect in old activated
neural stem cells and perturb them to boost the migration of old cells.
Aim 2 will evaluate the therapeutic potential of blocking a signaling pathway that is important for regulation of
cell migration and adhesion for repair upon stroke injury and explore the mechanisms by which it does so.
Together, these independent aims will contribute to the field by giving a mechanistic understanding of how age
causes a decline in neural stem cell function through dysregulation in cell migration and adhesion as well as
provide a potential therapeutic avenue for improving neurogenesis and recovery from stroke in old brains.
Through this work, I will be trained in the field of aging and neural stem cells as well as gain diverse expertise
in cutting-edge experimental approaches. My scientific training coupled with mentoring by physician-scientists
will help me in building a career as a physician-scientist interested in brain aging and treating patients with
neurological diseases.

## Key facts

- **NIH application ID:** 10750482
- **Project number:** 1F30AG077799-01A1
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Olivia Yu Zhou
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $40,168
- **Award type:** 1
- **Project period:** 2023-09-15 → 2026-12-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10750482

## Citation

> US National Institutes of Health, RePORTER application 10750482, Mechanisms underlying a decline in neural stem cell migration during aging (1F30AG077799-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10750482. Licensed CC0.

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