# Promoting Skeletal Regeneration in Aged Mice

> **NIH NIH P20** · TULANE UNIVERSITY OF LOUISIANA · 2020 · $281,636

## 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:** 9932384
- **Project number:** 5P20GM103629-09
- **Recipient organization:** TULANE UNIVERSITY OF LOUISIANA
- **Principal Investigator:** Mimi C Sammarco
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $281,636
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9932384

## Citation

> US National Institutes of Health, RePORTER application 9932384, Promoting Skeletal Regeneration in Aged Mice (5P20GM103629-09). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9932384. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*