# Understanding the role of mitochondria in the age-related decline in axon regeneration

> **NIH NIH R56** · UNIVERSITY OF FLORIDA · 2020 · $375,030

## Abstract

Axon regeneration is one of the essential processes that restore the nervous system after nerve injury
and neurodegeneration. Aging decreases axon-regeneration capacity while increasing the risk of axonal
damages. Failure of axonal regeneration following nerve injury can lead to permanent body-movement
impairment and various disabilities. Very little is known about the underlying mechanism of axon regeneration,
and there is no efficient treatment to enhance the function of damage neurons.
 The goal of this proposal is to identify an intrinsic mechanism underlying the age-related decline of axon
regeneration by investigating the responses of mitochondria to axonal damage and aging. Mitochondria
dynamically change in their morphology, motility, number, and activity by communicating with the nucleus of the
host cell to match local demand for energy and to maintain cellular and their own homeostasis. Our and others'
recent studies have found a clear link between axon-regeneration capacity and mitochondrial behavioral
changes in response to axonal damage. Our unpublished studies also suggest that axon regeneration is
regulated by ATFS-1, a key factor in the retrograde signaling from mitochondria to nucleus that mediates
mitochondrial unfolded protein response (mitoUPR). Adjusting mitochondrial response to axonal damage could
therefore be a critical determinant of axon regeneration. We do not know, however, the underlying mechanisms
of these mitochondrial responses to axonal damage and their roles in the age-related decline of axon
regeneration.
 To delineate these unmet needs, we will combine our expertise in C. elegans genetics, mitochondrial
biology, and in vivo laser axotomy at a single axon resolution. Specifically, we will use in vivo imaging approaches
to monitor the axonal trafficking of mitochondria and the activity of mitoUPR after axonal damage and during
aging on short-term and long-term scales. We will also use both in vivo and in vitro assays to quantitatively
measure the physiological properties of mitochondria that are altered by axonal injury signals and mitoUPR (Aim
1). We will use a laser-based axotomy and genetic approaches experimentally to change the nature of
mitochondria in aging animals to test the correlation with axon regeneration ability (Aim 2). Finally, we will perform
visual-based genetic approaches to discover a genetic mechanism that mediates mitochondrial localization and
traffic in neurons (Aim 3).
 We believe that these approaches will achieve a new understanding of the mechanisms that maintain
optimal function of the nervous system during aging by regulating mitochondrial function in aging and injured
neurons. Our findings will provide better insight into novel therapeutic approaches to restore neuronal function
after nerve injury.

## Key facts

- **NIH application ID:** 10230101
- **Project number:** 1R56AG066654-01
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** SUNG MIN HAN
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $375,030
- **Award type:** 1
- **Project period:** 2020-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10230101

## Citation

> US National Institutes of Health, RePORTER application 10230101, Understanding the role of mitochondria in the age-related decline in axon regeneration (1R56AG066654-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10230101. Licensed CC0.

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