# Role of Geroscience-Guided Therapeutics in Oral Health Problems of Aging

> **NIH NIH R03** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2022 · $153,500

## Abstract

Professional Development: This GEMSSTAR application describes 2 years training program to further my
career aspirations to become an independent dentist-scientist in geriatric oral health field. My goal is to gain
additional training under the leading scientists to achieve my ultimate goal of developing novel approaches
to treat/alleviate age-related TMJ degeneration. This award will support, guide and importantly facilitate my
following goals: (1) To acquire additional training in geroscience. (2) To complete the studies outlined in
Specific Aims and translate from bench research to clinic. (3) To develop a deeper collaboration with
multidisciplinary team. To achieve the listed goal, I have assembled a career advisory committee to help
develop my academic career in the most effective way. Also, my mentors in areas that are beyond my
current field of expertise will ensure the success of my projected aims.
Science: Aging affects all organs and tissues of the body and leads to many diseases, including TMJ
degeneration. TMJ degeneration significantly impair the quality of life by causing acute and chronic pain,
thus making this disease a global health issue and a financial burden of epidemic proportion. The United
States and the global ageing populations are projected to grow exponentially over the next several
decades, the incidence of the TMJ degenerative disorders is also expected to rise substantially. As there is
no effective treatment for the TMJ degeneration in an aged individual, there is an unmet clinical need for an
effective approach to treat TMJ degeneration associated with old age.
Our central hypothesis is that concurrent administration of senolytics and mechanical loading will have a
synergistic anabolic effect on the cartilage of TMJ. The hypothesis will be tested by following specific aims:
Aim 1: To determine if intermittent mechanical loading augments the beneficial effects of intermittent
senolytics on TMJ cartilage. We will utilize both male and female triple transgenic reporter mice (Col1a1X
Col2a1XCol10a1 triple transgenic reporter mice) following D+Q/vehicle treatment and mechanical
loading/unloading with botox. The micro-CT image, biomechanical testing, histomorphometry, RNA
sequencing, and pain measurement will be done to determine outcome. Aim 2: To define the biological
mechanism by which senolytics and intermittent mechanical loading alleviates TMJ degeneration in older
adults. We will leverage single cell transcriptomics (SCT) to reveal the heterogeneity and conserved
transcriptomic signatures of Col1a1 and Col10a1 cells in vivo in different experimental groups. We will
assess the percentage of Col1a1, Col2a1 and Col10a1 cells across different cell types (clusters) in different
experimental groups to gain insights on the conserved transcriptomic signature of Col1a1 and Col10a1
cells regardless of cell type, which could be invaluable for future drug development.

## Key facts

- **NIH application ID:** 10517869
- **Project number:** 1R03AG078897-01
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** Po-Jung Chen
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $153,500
- **Award type:** 1
- **Project period:** 2022-09-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10517869

## Citation

> US National Institutes of Health, RePORTER application 10517869, Role of Geroscience-Guided Therapeutics in Oral Health Problems of Aging (1R03AG078897-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10517869. Licensed CC0.

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