# Neural Stem Cell Aging and Neurodegeneration

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA BERKELEY · 2024 · $541,817

## Abstract

Project Summary
Perturbation of mitochondrial proteostasis, a form of mitochondrial stress, activates the mitochondrial unfolded
protein response (UPRmt), a retrograde signaling pathway leading to transcriptional up-regulation of
mitochondrial chaperones and stress relief. Recent advances in mitochondrial biology link UPRmt to lifespan
extension independently of oxidative stress and damage in model organisms. These observations beg the
questions of whether mitochondrial protein folding stress and the UPRmt regulate healthspan and lifespan in
mammals. We have recently identified a novel regulatory branch of the UPRmt. We will elucidate the
physiological significance of this pathway in regulating stem cell aging, tissue degeneration, and degenerative
diseases, such as Alzheimer’s disease. Using a gain-of-function approach, we will test the feasibility of
activating these molecules to extend healthspan during natural aging and ameliorate Alzheimer’s disease.
Collectively, these studies highlight a novel defense program that improves mitochondrial integrity and tissue
homeostasis. Successful completion of the proposed studies will provide a critical mechanistic understanding
of how mitochondria and metabolism regulate tissue homeostasis. In addition to generating important basic
knowledge, these studies will provide new targets for developing potential interventions for aging and aging-
associated diseases, including Alzheimer’s disease.

## Key facts

- **NIH application ID:** 10801170
- **Project number:** 1R01AG082105-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** DANICA CHEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $541,817
- **Award type:** 1
- **Project period:** 2024-03-01 → 2028-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10801170

## Citation

> US National Institutes of Health, RePORTER application 10801170, Neural Stem Cell Aging and Neurodegeneration (1R01AG082105-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10801170. Licensed CC0.

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