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Fatigue is a common symptom reported in those with chronic pain. Incidences of fatigue are prevalent in an aging population and may indirectly accelerate biological aging process. However, it is unknown whether biological markers of aging are associated with fatigue in those with chronic pain. We aimed to explore whether fatigue is associated with brain aging and epigenetic aging in middle-to-older age individuals with chronic pain. Chronic pain participants (57.8years ± 7.7; 62.2% female) who had fatigue (n=37) or no fatigue (n=105) completed self-reported pain questionnaires, a fatigue severity scale, a blood draw and an MRI scan. Using nominal (fatigue vs no fatigue) and continuous methods (fatigue severity), fatigue variables were evaluated alongside three epigenetic clocks previously associated with knee pain (DNAmAge, DNAmPhenoAge, and DNAmGrimAge), and two brain age prediction calculators …