# Delaware Center for Musculoskeletal Research - Wang

> **NIH NIH P20** · UNIVERSITY OF DELAWARE · 2023 · $867,011

## Abstract

PROJECT SUMMARY
Aging is a major driver of neurodegenerative disorders such as Parkinson’s disease (PD) and skeletal
diseases including osteoporosis, which inflict significant economic burdens and suffering on the healthcare
system, patients, and their caregivers. Recent clinical and animal studies suggest that the two diseases share
a common etiology, i.e., the accumulation of senescent cells. Thus, pharmaceutical clearance of senescent
cells is being actively pursued in both fields using various senolytic compounds. However, despite the intrinsic
links between the brain and bone, the evaluation of the treatment outcomes has been narrowly focused on
either the neural or skeletal system alone. Emerging evidence demonstrates that senolytics elicit tissue- and
cell-specific responses. There is an urgent need for a holistic evaluation of senolytic effects on both organ
systems. Furthermore, clinical practice and preclinical investigation clearly show the benefits of moderate
exercise in delaying age-associated diseases and improving brain and bone functions. Thus, exercise could
be complementary to senolytics for PD and osteoporosis treatment. However, the synergy between exercise
and senolytics has not been investigated. To fill this knowledge gap, we propose a team science project that
will take a multi-disciplinary approach. Taking the advantage of the team’s complementary expertise in PD
animal models and senolytics (Kim), bone mechanobiology and exercise (Wang), and mouse brain in vivo MRI
(Chow), we will test the hypothesis that senolytic ABT-263 decreases the senescent cell burden in both brain
and bone tissues of aged PD mice based on a critical time-window and cell-type specificity, and the treatment
mitigates the secondary damages from senescent cells, leading to favorable local cellular and biochemical
environments for brain and skeletal cells. We further hypothesize that subsequent exercise like treadmill
running provides additional protection and acts in synergy with senolytics in protecting bone and brain from
degeneration in aged PD mice. To test the hypotheses, our specific aim is to holistically evaluate the bone
and brain responses to senolytic ABT-263 treatment alone or in combination with treadmill running at the cell,
tissue, and brain circuit levels in a novel PD mouse model. Alignment with the Parent Project: The proposed
work will test a novel dual-treatment in PD patients with the goal of improving the musculoskeletal function, a
focus of the parent COBRE. Future plans: The completion of the supplement will strengthen the synergy
among the three research groups and further propel the momentum of collaboration that has been built up
during the preparation of the supplement. We will leverage the resources and expertise through the parent
COBRE and existing INBRE at UD and DSU, a prominent HBCU in Delaware. The team sets their goal of
developing a larger multi-PI R01 project to further optimize treatments for PD and osteoporoti...

## Key facts

- **NIH application ID:** 10854179
- **Project number:** 3P20GM139760-03S2
- **Recipient organization:** UNIVERSITY OF DELAWARE
- **Principal Investigator:** DAWN M ELLIOTT
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $867,011
- **Award type:** 3
- **Project period:** 2021-02-15 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10854179

## Citation

> US National Institutes of Health, RePORTER application 10854179, Delaware Center for Musculoskeletal Research - Wang (3P20GM139760-03S2). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10854179. Licensed CC0.

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