Abstract
DunedinPACE quantifies the pace of biological aging. No study has examined its association with cardiorespiratory fitness (CRF). Additionally, the physiologically relevant CRF thresholds associated with slow aging remain unclear. The purpose of this study was to investigate the association between CRF and the pace of epigenetic aging, as measured by DunedinPACE, and to identify a CRF threshold indicative of slower biological aging. Here, we analyzed data of 144 older men (aged 65–72 years) enrolled in the WASEDA’S Health Study to examine the association of CRF (VO₂/kg at peak and ventilatory threshold (VT)), physical fitness, anthropometric parameters, and nutritional intake with epigenetic aging. Epigenetic aging was assessed using DunedinPACE derived from blood DNA methylation profiles. We performed Pearson’s and partial correlation analyses adjusted for age, smoking status, and drinking status, followed by receiver operating characteristic (ROC) curve analyses with bootstrapped optimal cutoff determination. In the unadjusted analyses, VO₂/kg at peak ( r = − 0.17, p = 0.041) and VT ( r = − 0.17, p = 0.046) were inversely associated with DunedinPACE, and VO₂/kg at peak showed a significant association even in the adjusted models ( r = − 0.16, p = 0.046). The ROC curve analysis revealed a potential threshold of VO₂/kg at peak (26.2 mL/kg/min) for differentiating individuals with slower biological aging, supported by bootstrap distributions of optimal cutoff points and Youden’s index. This study suggests that higher CRF is associated with a slower pace of epigenetic aging, as measured using DunedinPACE. The identified VO₂peak threshold may provide a biomarker-based fitness target to support healthy aging in older adults.