# Promoting Skeletal Regeneration in Aged Mice

> **NIH NIH P20** · TULANE UNIVERSITY OF LOUISIANA · 2021 · $122,889

## Abstract

Promoting Skeletal Regeneration in Aged Mice 
Summary 
In this study we will investigate the mechanisms behind failed bone and soft tissue regeneration in the aged 
digit amputation mouse model. While the digit regeneration model has gained considerable traction in recent 
years and resulted in a substantial amount of knowledge regarding mechanisms underlying regeneration, this 
is the first study that will use this model to explore regeneration the context of aging. We show that 
regeneration fails in this model in ways that are similar to compromised bone turnover in old age, including 
exacerbated bone degradation activity and the attenuated ability to mount a successful regenerative bone 
response. This age-related response is similar to the one seen when we applying increased oxygen tension, 
disrupting the native oxygen microenvironment in the regenerating digit, which requires an oscillation between 
both hypoxic and normoxic oxygen environments for successful regeneration. While it is clear that the oxygen 
microenvironment of the digit is dynamic and critical to successful regeneration, it is not known how oxygen 
cues the regenerative process and whether or not this is directly linked to changes in cell metabolism or 
metabolic switching, as is seen in certain cancers. The studies outlined in this project will explore the 
mechanisms through which regeneration fails during aging by specifically investigating the role of oxygen 
signals and cellular metabolism. We will test the hypothesis that regeneration fails in aging as a direct 
result of the inability of key cell populations to successfully execute metabolic switching between 
mitochondrial respiration and glycolytic activity and to respond to changes in the oxygen 
microenvironment. To test this hypothesis we will evaluate regeneration in both aged outbred mice (Aim 1) 
and in a transgenic mouse model of aging with metabolic syndrome (Aim 2), and test the ability of these two 
strains of mice to respond effectively to changes in oxygen levels (Aim 3). This project will provide valuable 
data in both the regeneration and aging fields and will yield new mechanistic insights that will help guide future 
therapeutic intervention.

## Key facts

- **NIH application ID:** 10173809
- **Project number:** 5P20GM103629-10
- **Recipient organization:** TULANE UNIVERSITY OF LOUISIANA
- **Principal Investigator:** Mimi C Sammarco
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $122,889
- **Award type:** 5
- **Project period:** 2012-08-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10173809

## Citation

> US National Institutes of Health, RePORTER application 10173809, Promoting Skeletal Regeneration in Aged Mice (5P20GM103629-10). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10173809. Licensed CC0.

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