# Inflamm-aging of osteoprogenitor cells: A therapeutic target for improved bone healing - Resubmission - 1 - Revision - 3

> **NIH NIH R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2021 · $72,154

## Abstract

PARENT GRANT ABSTRACT
Aging has a dramatic effect on regeneration of all tissues, bone included. When a young adult fractures a
bone, stem cells residing within the bone marrow cavity proliferate and differentiate into osteoblasts. This
process results in regeneration of the skeletal element with complete restoration of its biomechanical
properties. In the elderly, however, this process is often inadequate, which will result in a delayed healing
response and subsequent medical complications.
Chronic inflammation mediated by activation of the NF-κB pathway has recently been linked to a decline in
regenerative potential in aged skin, skeletal muscle and nervous system, although the direct effects of NF-κB
activation on stem cell function in these tissues is still under investigation. Accumulation of senescent cells in
aging tissues has been suggested as the driver of chronic inflammation, as these cells secrete inflammatory
factors, which affect the entire surrounding cellular milieu, further stimulating inflammation.
The mechanisms underlying this age-related decline in stem cell function are the focus of this proposal. We
hypothesize that the accumulated effects of chronic inflammation lead to osteoprogenitor cell dysfunction.
Within this proposal, we will quantify and qualify age-dependent alterations in progenitor cell frequency,
proliferative and osteogenic differentiation potential, and determine if these changes are caused by
chronological aging or age-associated inflammation. While previous studies have demonstrated a reduced
regenerative potential of heterogeneous bone grafts from aged animals, this study will for the first time assess
the affect of aging on a homogeneous progenitor cell population in an in vivo environment.
In the second part of this proposal, we will investigate the underlying mechanism of action that is
responsible for increased osteoprogenitor cell senescence and resulting regenerative dysfunction.
Here, we will identify the machinery that activates telomere dysfunction and cell senescence. From this
experiment, we will learn, whether chronic inflammation is the culprit for reduced regenerative function of the
aged bone progenitor cell, and whether this process is reversible. Finally, we will study the effect of chronic
inflammation on the regenerative decline of the aging osteoprogenitor cell in a regenerative context
and will utilize the information gained in the previous aims to design a therapeutic approach that will lead to the
rejuvenation of skeletal progenitor cells.
The goal of this highly translational project is to identify the basis of the age-related decline in osteogenic
progenitor cell function and thus to define a new therapeutic target for improved bone healing in the elderly
patient.

## Key facts

- **NIH application ID:** 10365117
- **Project number:** 3R01AG056169-04S1
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Philipp Leucht
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $72,154
- **Award type:** 3
- **Project period:** 2018-03-15 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10365117

## Citation

> US National Institutes of Health, RePORTER application 10365117, Inflamm-aging of osteoprogenitor cells: A therapeutic target for improved bone healing - Resubmission - 1 - Revision - 3 (3R01AG056169-04S1). Retrieved via AI Analytics 2026-06-02 from https://api.ai-analytics.org/grant/nih/10365117. Licensed CC0.

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