# Accelerated Metabolic Aging in Rheumatoid Arthritis Immune cells and Skeletal Muscle: A Pilot Study

> **NIH NIH R03** · DUKE UNIVERSITY · 2021 · $161,000

## Abstract

Project Summary/Abstract
Rheumatoid arthritis (RA) is a model disease for studying premature aging. Despite revolutionary
improvements in anti-inflammatory treatments over the past few decades, persons with RA continue to suffer
from early aging-associated metabolic comorbidities, evidenced by an increased risk of sarcopenic obesity,
insulin resistance, atherosclerosis and mortality. RA and aged immune cells have abnormal metabolic and
mitochondrial function, which coincide with immune dysregulation. Skeletal muscle in both RA and aging is
also marked by altered metabolism. In the proposed study, I will investigate whether dysfunction of
mitochondria, the cellular metabolic “engine,” connect RA peripheral helper T-cells, inflammatory macrophages
and skeletal muscle abnormalities. My objectives for this pilot, feasibility study are twofold: 1) to determine
whether RA peripheral T cell, macrophage and skeletal muscle mitochondrial function abnormalities are
associated and 2) to determine the effects of exercise training on RA peripheral immune cell and skeletal
muscle mitochondria. I hypothesize that 1) metabolic alterations in RA immune cells and skeletal muscle are
interconnected, driven either by interorgan crosstalk or by master metabolic regulation; and 2) that
interventions targeting global mitochondrial dysfunction will improve both cardiometabolic comorbidities and
autoimmune disease in RA.
As a first step to test my hypotheses in this pilot study, I will compare peripheral naïve CD4+ T cell and
inflammatory macrophage mitochondrial respiratory function to permeabilized muscle fiber mitochondrial
respiratory function and near-infrared spectroscopy muscle oxidative capacity measurements in older persons
(ages 55-85 years) with seropositive or erosive RA (n=10). I will also compare these immune cell and muscle
mitochondrial function assessments in RA to age-, sex-, BMI-matched healthy controls (n=10). Additionally,
using existing frozen samples, I will assess mitochondrial function responses to exercise training from 12
persons (age range 52-80) with RA that underwent a 10-week high intensity interval training exercise program.
I will then use stored baseline and post-training immune cells and muscle tissue for mitochondrial function
assessments in peripheral blood mononuclear cells and skeletal muscle. I expect that findings from this pilot
study will provide a framework for my future research on interorgan metabolic regulation and mitochondrial
adaptation to exercise training in both aging and RA. My results promise to increase scientific knowledge of the
connections between two main “pillars of aging”: inflammation and metabolism.

## Key facts

- **NIH application ID:** 10237366
- **Project number:** 5R03AG067949-02
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Brian James Andonian
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $161,000
- **Award type:** 5
- **Project period:** 2020-08-15 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10237366

## Citation

> US National Institutes of Health, RePORTER application 10237366, Accelerated Metabolic Aging in Rheumatoid Arthritis Immune cells and Skeletal Muscle: A Pilot Study (5R03AG067949-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10237366. Licensed CC0.

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