The effect of the integrated stress response reduction intervention on cellular aging in middle-aged nurses: a pilot study

Nurses experience persistently high levels of occupational stress, which negatively impacts their health and the quality of patient care. Chronic psychological stress is closely linked to physiological dysregulation and cellular aging processes through stress-response pathways. However, limited evidence exists regarding whether stress management interventions targeting these mechanisms can influence cellular aging biomarkers in nurses. This study evaluated the effects of an Integrated Stress Response Reduction Intervention ( i SRI) on cellular aging among middle-aged nurses. A non-randomized controlled pilot study was conducted with 60 nurses aged 45–60 years recruited from two tertiary hospitals. Participants were allocated to either an intervention group ( n = 31) or a control group ( n = 29). The 12-week i SRI comprised biofeedback, cognitive–behavioral education, mindfulness, and exercise. Outcomes included perceived stress levels and biochemical markers (serum cortisol, IL-6, and SOD). Cellular aging was assessed via leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNAcn) using qPCR. Following the intervention, the i SRI group showed a significant decrease in perceived stress levels, with a significant group ⋅ time interaction ( p =.012). Regarding biochemical markers, serum cortisol showed a significant group ⋅ time interaction ( p =.001), although no significant between-group difference was observed post-intervention. SOD levels increased significantly in the intervention group compared to the control group ( p =.031), showing a robust interaction effect ( p =.001). Regarding cellular aging markers, a significant between-group difference in LTL was observed post-intervention ( p =.002), and this difference remained significant after controlling for covariates ( p =.047). However, the longitudinal effect for LTL was not statistically significant ( p =.263). No significant changes were observed in IL-6 and mtDNAcn. The 12-week i SRI demonstrated an initial protective effect on preserving LTL, which was associated with reductions in perceived stress and subsequent improvements in cortisol and SOD. These findings suggest that mechanism-based stress management may help support telomere preservation, a hallmark of cellular aging. Given the exploratory nature of this pilot study, further larger-scale randomized controlled trials are warranted to confirm whether such interventions can induce sustained shifts in biological aging trajectories. The study was registered in CRIS (KCT0011526; registration date: 23 January 2026; retrospectively registered).