The Effect of Exercise on T Cell Aging in Rheumatoid Arthritis
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Abstract Exercise training is linked to beneficial effects on maladaptive immune aging. In patients with rheumatoid arthritis (RA), exercise training is a disease modulating therapy and may improve premature biological aging inherent in RA, however, the mechanisms by which exercise benefits immune health is poorly understood. Improved knowledge of the specific types of exercise and the mechanisms by which exercise reduces disease activity in RA will enhance clinical care for older adults with chronic inflammatory conditions. Further, this work has potential to generalize to improving immune function in older adults without inflammatory conditions. My career goal is to lead a comprehensive exercise rheumatology translational research program to study the effects of exercise on disease-promoting immune-aging pathways and personalized lifestyle prescriptions for older patients with rheumatic disease. I plan to gain the training and experience to become a leader in exercise rheumatology studying lifestyle interventions for improving immune aging in chronic inflammatory diseases. In particular, I will complete three objectives to address the key gaps in my career development training: 1) develop geroscience-specific competency in clinical aging research assessments; 2) acquire skills in translational aging science statistical analysis; and 3) cultivate clinical-translational aging research leadership skills. Further, I will achieve my career development plan with expert guidance of my mentors and collaborators at the Duke Molecular Physiology Institute and Duke Aging Center. In the proposed study, I will investigate whether exercise training-induced benefits to RA are linked to improvements in T cell function, T cell mitochondrial oxidative metabolism, and markers of T cell aging. In Aim #1 and Aim #2, I will utilize data from a NIH-funded randomized, controlled trial to determine if compared to lifestyle counseling, a remotely supervised caloric restriction and exercise training (CRET) program leads to greater improvement in RA regulatory T cell function and metabolism (Aim #1) and T cell aging (Aim #2). In Aim #3, I will perform an independent pilot study to inform future investigations on the best exercise doses and intensities to improve RA immune aging. To this end, I will determine if a remotely supervised high-intensity aerobic exercise training intervention is safe, acceptable, and feasible. Results from my Aim #3 pilot study will inform my planned R01 randomized controlled trial proposal comparing remotely supervised moderate- versus high-intensity aerobic exercise training on RA immunoregulatory function and immune aging. With successful completion of this K23 project, I will bridge the gap to achieving my career goal of becoming a leader in aging science and physical activity interventions for older patients with RA and chronic inflammatory diseases.
