Association between habitual physical activity and mitochondrial DNA copy number in healthy middle-aged adults

Abstract Mitochondrial dysfunction is linked to metabolic disturbances, and mitochondrial DNA copy number (mtDNAcn) is widely recognized as an accessible biomarker of mitochondrial content and capacity. Although physical activity (PA) may support mitochondrial health, its relationship with mitochondrial function remains unclear. This study examined the association between PA and mtDNAcn in middle-aged South Korean adults. This cross-sectional study included 256 community-dwelling middle-aged adults. Subjective PA was assessed using the Korean version of the International Physical Activity Questionnaire Short Form, and objective PA using ActiGraph wGT3X-BT accelerometers over three consecutive weekdays. The mtDNAcn was quantified in whole blood using a qPCR-based assay. Pearson correlation and multiple linear regression adjusting for covariates were performed using SPSS 29.0. Subjective total PA and walking PA (metabolic equivalent of the task [MET]-min/week) and objectively measured light-intensity PA (LPA) were positively associated with mtDNAcn levels ( p < 0.05), whereas sedentary time, moderate-to-vigorous PA were not. After adjustment for demographic and lifestyle covariates, total PA(β = 0.16), subjective walking PA(β = 0.15), and objectively measured LPA(β = 0.19) remained significantly associated with higher mtDNAcn levels. These findings suggest that habitual PA, particularly at lower intensities, such as walking and light activity, is associated with higher leukocyte mtDNAcn levels in middle-aged adults. Given the cross-sectional design, longitudinal studies are needed to clarify the direction of this association.