Impact of 14 weeks combined exercise on serum cadmium levels, DNA methylation, and epigenetic aging in older women

Abstract

Introduction: Cadmium is a toxic heavy metal linked to impaired cardiorespiratory fitness and altered DNA methylation patterns. This study investigated the effects of 14 weeks of combined exercise training on epigenetic modifications and blood cadmium levels in women with varying aerobic fitness. Methods: Participants underwent three weekly training sessions totaling 180 minutes. Pre- and post-intervention evaluations included anthropometry, blood pressure, physical performance, and heavy metal analysis. DNA methylation was assessed using the Illumina EPIC BeadChip. Results: Based on baseline 6-minute walk test and age, participants were divided into lower (LAF, n = 32) and higher (HAF, n = 17) aerobic fitness groups. Pre-intervention, LAF had significantly higher cadmium levels than HAF (p = 0.003). After the intervention, LAF showed a significant reduction of 0.056 µg/L (63%), while HAF decreased by 0.019 µg/L (28%) (p = 0.046). A total of 513 differentially methylated regions (DMRs) related to cadmium were identified, with enrichment in pathways associated with neurodegeneration-related processes. Intrinsic epigenetic age acceleration (IEAA) also differed significantly between groups at baseline. Conclusion: Combined exercise training significantly reduced cadmium levels in women aged 50–70 years with low aerobic fitness and induced locus-specific epigenetic changes associated with cadmium-related pathways, which may be relevant to pathways implicated in age-related neurological conditions. Clinical Trial: The study was registered in the Brazilian Clinical Trials Registry (ReBEC; identifier RBR-3g38dx).