# Systemic contribution of age-associated epigenetic mechanisms to osteoarthritis

> **NIH NIH R01** · HEBREW REHABILITATION CENTER FOR AGED · 2022 · $425,515

## Abstract

PROJECT SUMMARY
Osteoarthritis (OA) is the most common form of arthritis in the United States and a leading cause of physical
disability in older individuals. There are no approved pharmacologic treatments available beyond those for
symptomatic relief. Thus, identifying new treatment targets is critical to reducing the burden of OA. While age
is one of the strongest predictors of OA, the disease mechanisms that underlie the relationship between
cellular and molecular hallmarks of aging and OA are unclear. The long-term goal of this ancillary study is to
identify potential new targets for OA therapy by identifying key age-associated biological mechanisms
underlying OA pathogenesis. The objective of this project is to determine the role of epigenetic changes to
genes in key aging pathways on OA. The central hypothesis is that aging is associated with epigenetic
modifications affecting DNA methylation levels in immune blood cells (i.e., `inflammaging') and will be
associated with greater burden of disease across commonly affected synovial joints, including the hands,
knees and hips. Epigenetic modifications that affect downstream changes in gene and protein expression
without altering the DNA sequence may provide important insights into OA pathogenesis that are not captured
by information on genetic or environmental risk factors. The contribution of age-related epigenetic
mechanisms to OA burden will be assessed in the MOST study, an ongoing well-characterized cohort of
individuals with and without early stage knee OA. The pending reexamination of MOST subjects presents a
unique, time-sensitive opportunity to obtain contemporaneous measures of epigenetic markers and OA burden
that includes assessments of hand OA from radiographs. New acquisition of hand radiographs will be
combined with the ongoing radiographic imaging of knees and hips to constitute a multiple joint OA phenotype.
The acquisition of hand radiographs and genome-wide DNA methylation will make it possible for the first time
in MOST to study the relation of epigenetic factors with multiple joint OA. Aims of the study include 1)
determining whether epigenetic age acceleration is associated with multiple joint OA by assessing the
difference between chronological age and epigenetic molecular age, then relating this to multiple joint OA and
2) identifying novel epigenetic markers associated with multiple joint OA by performing an epigenome-wide
association study, then pathway analyses and hierarchical clustering to identify whether differentially
methylated loci and OA subtypes are enriched for biological pathways related to aging. The expected outcome
is identification of age-associated epigenetic mechanisms that underlie OA pathogenesis, which is needed to
identify relevant OA treatment targets and biomarkers that could be used to identify at-risk individuals earlier in
the disease process before the onset of structural changes in the joint. The proposed ancillary study will also
provide ...

## Key facts

- **NIH application ID:** 10465071
- **Project number:** 5R01AR075356-04
- **Recipient organization:** HEBREW REHABILITATION CENTER FOR AGED
- **Principal Investigator:** Michelle Szu-Huei Yau
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $425,515
- **Award type:** 5
- **Project period:** 2019-09-09 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10465071

## Citation

> US National Institutes of Health, RePORTER application 10465071, Systemic contribution of age-associated epigenetic mechanisms to osteoarthritis (5R01AR075356-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10465071. Licensed CC0.

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