RESULTS: Among 1587 participants in the analysis, 187 participants had higher eGFR decline rate. According to the comparison of methylation in participants with different eGFR declines and at different ages, respectively, we identified common hypermethylated genes, including DNMT3A and GGACT, as well as hypomethylated genes such as ARL6IP5, CYB5D1, BCL6, RPRD2, ZNF451, and MIAT in both participants with higher eGFR decline and those of older age. We observed associations between the methylation status of signaling pathways and aging as well as renal function decline. These pathways notably included autophagy, p38 mitogen-activated protein kinases, and sirtuins, which were associated with autophagy process and cytokine production.
CONCLUSIONS: Through methylation analysis of PBMCs, we identified genes and signaling pathways which could play crucial roles in the interplay of renal aging and renal function decline. These findings contribute to the development of novel biomarkers for identifying at-risk groups and even for therapeutic agent discovery.
结果:在分析的1587名参与者中,187名参与者的eGFR下降率较高。根据不同eGFR下降和不同年龄参与者的甲基化比较,分别,我们确定了常见的高甲基化基因,包括DNMT3A和GGACT,以及低甲基化基因如ARL6IP5,CYB5D1,BCL6,RPRD2,ZNF451和MIAT在eGFR下降较高的参与者和年龄较大的参与者中.我们观察到信号通路的甲基化状态与衰老以及肾功能下降之间的关联。这些途径特别包括自噬,p38丝裂原活化蛋白激酶,和sirtuins,与自噬过程和细胞因子产生有关。
结论:通过PBMC的甲基化分析,我们确定了可能在肾脏衰老和肾功能下降的相互作用中起关键作用的基因和信号通路。这些发现有助于开发新的生物标志物,用于识别风险群体,甚至用于发现治疗剂。