Impact of combined exercise on blood DNA methylation and physical health in older women with obesity

by Atchara Dawangpa, Pitaksin Chitta, Guilherme da Silva Rodrigues, Nutta Iadsee, Natália Y. Noronha, Carla B. Nonino, Carlos R. Bueno Júnior, Chanachai Sae-Lee

This study examined the effects of a 14-week combined exercise program on blood DNA methylation (DNAm) and its potential biological pathways in normal-weight, overweight, and obese older women. A total of 41 participants were assessed at baseline, 7 weeks, and 14 weeks into the training. Their whole-blood DNAm profiles were measured using the Infinitum MethylationEPIC BeadChip, alongside physical and biochemical health evaluations. The results showed notable health improvements, with decreases in blood pressure and cholesterol levels in the overweight and obese groups. Blood triglycerides were reduced only in the overweight group. Physical performance also improved across all groups. At 14 weeks, 1,043 differentially methylated positions (DMPs) were identified, affecting 744 genes. The genes were linked to biological processes, such as cellular metabolism, with significant pathway enrichment related to oxidative phosphorylation and chemical carcinogenesis. Additionally, the overweight group experienced significant reductions in methylation levels at eight lipogenesis-related genes. Protein EpiScore analysis revealed decreased levels of CCL11, VEGFA, and NTRK3 proteins at 14 weeks compared to baseline. Despite these significant molecular changes, there was no observable difference in DNAm age after the intervention. This study highlights how combined exercise can modify DNAm patterns in older women, particularly in lipogenesis-related genes, but suggests that further research is needed to understand the full implications for biological ageing.