# Autophagy in aging and neurodegeneration

> **NIH NIH R00** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2022 · $248,999

## Abstract

Project Summary/Abstract
Neurodegenerative diseases have become enormous financial and societal burdens as human life expectancy
has increased. Misregulation of autophagy has been implicated in neurodegenerative disorders, including
Alzheimer's disease, Parkinson's disease and Huntington's disease. While many studies have characterized
autophagy and its role in cellular homeostasis in yeast and mammalian cell culture, much less in known about
autophagy in neurons, especially in the context of intact, living animals. Autophagosome biogenesis decreases
with age in mammalian primary neurons; the kinetics of autophagosome assembly factors also become
disrupted in primary neurons from aged mice (Stavoe et al., under peer review). Understanding how all stages
of autophagy change with age and how autophagy is regulated during aging will be important for developing
treatments for age-related neurodegenerative diseases. Furthermore, uncovering how aging modulates
autophagy in living animals, with intact nervous systems, will take into account the complex, dynamic natural
environment in which neurodegenerative diseases develop. The identification of age-related alterations in the
autophagy pathway and how autophagy is modulated with age will be conducted under the guidance of Dr.
Erika Holzbaur (mentor, University of Pennsylvania), a world expert in neuronal autophagy and trafficking. The
PI will collaborate with world experts in super-resolution microscopy (Drs. Melike Lakadamyali and Andrea
Stout, UPenn) and viral gene transfer (Dr. John Wolfe, UPenn) to learn new state-of-the-art approaches to
incorporate into the project.
The PI has assembled an excellent research advisory committee who will provide the training, support, and
mentoring to facilitate the proposed studies and growth of the PI. The PI will be based at the University of
Pennsylvania, under the guidance of Dr. Erika Holzbaur during the entire period of the mentored award. In
addition, the PI has access to state-of-the-art facilities and equipment, as well as excellent resources for career
development at the University of Pennsylvania. The proposed research and development plan will enable the
PI to characterize the age-related alterations to the autophagy pathway and determine how autophagy is
regulated in both primary mammalian neurons and C. elegans neurons in vivo. This initial research will allow
the PI to then modulate neuronal autophagy in vivo in both murine and C. elegans models of aging and
neurodegeneration, thus creating a niche for the PI as an independent faculty member. These studies will
determine potential molecular targets for improving the healthspan of the nervous system in the context of
aging and neurodegeneration. The proposed studies are part of the PI's long-term goal to investigate the
evolutionarily conserved molecular mechanisms of neuronal aging and neurodegeneration, with a particular
focus on neuronal autophagy, and to apply these discoveries to ameliorating ne...

## Key facts

- **NIH application ID:** 10401942
- **Project number:** 5R00NS109286-04
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** ANDREA STAVOE
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $248,999
- **Award type:** 5
- **Project period:** 2018-09-30 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10401942

## Citation

> US National Institutes of Health, RePORTER application 10401942, Autophagy in aging and neurodegeneration (5R00NS109286-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10401942. Licensed CC0.

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