# Dissecting the aging skeletal stem cell niche

> **NIH NIH R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2024 · $657,143

## Abstract

PROJECT SUMMARY
Maintenance, remodeling, and repair of the adult body is mediated by multipotent stem cells that give rise to a
variety of cell types that comprise the tissue in which they reside. During aging, there is a decline in homeostatic
and regenerative capacity leading to progressive degeneration of the structure and function of vital organs. In
particular, musculoskeletal degeneration is common in the elderly and leads to increased fracture risk and
reduced efficiency of fracture repair that drastically decreases quality of life. Our previous studies showed that
an age-associated increase in chronic, low-grade inflammation is the main cause of skeletal stem and progenitor
cell (SSPCs) dysfunction. Thus, we hypothesize that reducing pro-inflammatory signals and enhancing anti-
inflammatory activity will rescue SSPC number and osteogenic function in aged individuals. To investigate this,
we will first precisely define the molecular mechanisms regulating the inflammatory response in SSPCs,
and the role of anti-inflammatory factors in the resolution of inflammation. We will determine how these
mechanisms and the interaction between opposing pro- and anti- inflammatory signals is affected by aging.
These experiments will generate insights into the elements driving bone degeneration and identify
therapeutic targets to improve bone health and fracture repair in elderly patients. Our strong preliminary
experiments also identified two prime suspects involved in SSPC deterioration during aging. We will perform
gain and loss of function experiments in SSPCs to elucidate their specific role in the control of stem cell
self-renewal and differentiation. As manipulation of these factors can affect the extracellular inflammatory
milieu, we will use single-cell RNA-sequencing to determine their cell-intrinsic function in SSPCs and also their
influence on defined populations within the local niche. Finally, we will manipulate candidate expression
following injury in aged animals to assess their ability to rescue stem cell regenerative capacity and
improve bone healing.

## Key facts

- **NIH application ID:** 10833285
- **Project number:** 1R01AG086058-01
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Philipp Leucht
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $657,143
- **Award type:** 1
- **Project period:** 2024-08-01 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10833285

## Citation

> US National Institutes of Health, RePORTER application 10833285, Dissecting the aging skeletal stem cell niche (1R01AG086058-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10833285. Licensed CC0.

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