Probe IDs for protein EpiScore.

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.本研究探讨了为期14周的联合运动方案对体重正常、超重及肥胖老年女性血液DNA甲基化（DNAm）及其潜在生物学通路的影响。共计41名受试者在训练基线、第7周及第14周时接受评估。研究采用Infinitum MethylationEPIC微珠芯片检测其全血DNA甲基化谱，并同步开展身体与生化健康评估。结果显示受试者健康状况得到显著改善：超重与肥胖组的血压及胆固醇水平均有所降低；仅超重组的血液甘油三酯水平出现下降。所有组别受试者的身体机能均得到提升。干预14周后，共鉴定出1043个差异甲基化位点（DMPs），涉及744个基因。这些基因参与细胞代谢等生物学过程，其中氧化磷酸化与化学致癌作用通路富集显著。此外，超重组的8个脂肪生成相关基因的甲基化水平显著降低。蛋白质表观评分（EpiScore）分析显示，相较于基线，干预14周后受试者体内CCL11、VEGFA及NTRK3蛋白水平有所下降。尽管观测到上述显著的分子变化，但干预后受试者的DNA甲基化年龄（DNAm age）未出现可观测的差异。本研究证实联合运动可改变老年女性的DNA甲基化模式，尤其是脂肪生成相关基因，但仍需开展进一步研究以明确其对生物衰老的完整影响。