# Establishment of a human, age-specific model for axon growth and regeneration studies

> **NIH NIH R21** · UNIVERSITY OF WISCONSIN-MADISON · 2020 · $441,009

## Abstract

Human spinal cord injury leads to life-long disability, with limited treatment options despite decades of
research in rodents. Recent evidence indicates that there are fundamental differences in gene expression
between human and mouse, suggesting a critical need for identification of novel or human-specific candidates
as targets to increase axon regeneration following spinal cord injury. Additionally, in vitro studies of axon
growth are typically performed in neurons from embryonic or young postnatal rodents, ages with increased
intrinsic growth ability, and a very different transcriptional landscape from adult neurons. Thus, we propose to
create an age-relevant, human model for axon growth and regeneration.
 Recent technological advances now allow for human adult somatic cells to be reprogrammed into stem
cells, and then differentiated into neurons. However, reprogramming these cells through pluripotency has been
shown to erase the “age” of the original cell, resulting in a more embryonic identity of the resulting neuron.
Using a direct reprogramming protocol, we will transdifferentiate neonatal, ~35 year old, and ~70 year old
human somatic cells directly into neurons through overexpression of specific neuronal factors, allowing for
maintenance of the cell’s biological age identity. We will determine the maintenance of age in these cells at the
level of the epigenetic age signature, gene expression, and markers of cellular aging. As the first study of axon
growth in age-maintained human neurons, we will characterize the basal axon growth behavior on permissive
and inhibitory substrates to identify if age plays a role in human axon growth ability. To test this new resource,
we will target 20 different genes and pathways previously identified in other species to regulate axon growth for
their conservation in function in human neurons. In rodents it has recently been shown that certain axon growth
modifiers such as PTEN knockout, do not function similarly in aged animals as young animals (Geoffroy et al,
2016). Thus, we will utilize our age-maintained human iNs to determine if age drives changes in axon growth
phenotypes.
 Completion of this research will 1) establish a new human, age-relevant cell culture system for axon
growth studies, 2) identify genes and their regulators that have conserved functions in human neurons, and 3)
determine the role age plays in axon growth ability. Identification of translational targets specifically in human
neurons ultimately may lead to the development of effective therapeutic targets for human spinal cord injury.

## Key facts

- **NIH application ID:** 9978418
- **Project number:** 1R21NS111192-01A1
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Darcie Leann Moore
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $441,009
- **Award type:** 1
- **Project period:** 2020-05-01 → 2022-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9978418

## Citation

> US National Institutes of Health, RePORTER application 9978418, Establishment of a human, age-specific model for axon growth and regeneration studies (1R21NS111192-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9978418. Licensed CC0.

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