Heterogeneity of increased biological age in type 2 diabetes correlates with differential tissue DNA methylation, biological variables, and pharmacological treatments.
Heterogeneity of increased biological age in type 2 diabetes correlates with differential tissue DNA methylation, biological variables, and pharmacological treatments.
复制标题
2 型糖尿病中生物年龄增加的异质性与差异组织 DNA 甲基化、生物变量和药物治疗相关。
DOI：
10.1007/s11357-023-01009-8
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发表时间：
2024
期刊：
影响因子：
5.6
通讯作者：
Aguayo-Mazzucato,Cristina
中科院分区：
文献类型：
--
作者：
Cortez,BrianaN;Pan,Hui;Hinthorn,Samuel;Sun,Han;Neretti,Nicola;Gloyn,AnnaL;Aguayo-Mazzucato,Cristina
生物学年龄(BA)在细胞水平上密切地描述了与年龄相关的变化。当使用临床生物标记物计算时，2型糖尿病(T2D)加速BA，但T2D中个体年龄加速的幅度有很大的差异，这表明其他因素对BA有贡献。此外，BA是否会随着治疗而改变还不清楚。我们假设，T2D中BA异质性分布的潜在决定因素可能是由于不同的组织老化，如DNA甲基化(DNaM)水平所反映的，或者生物变量及其各自的治疗方法。使用dNaM表型年龄(DNAmPhenoAge)算法获得公开可用的dNaM样本来计算BA。DNAmPhenoAge在全血、胰岛和肝脏的T2D样本中显示年龄加速，但在脂肪组织和骨骼肌中没有。对差异甲基化CpG位点相关基因的分析发现，8个单独的CpG甲基化位点与基因表达显著相关。来自NHANES 2017-2018年和ACCORD队列参与者的临床生物标记物被用来使用Klmera和Doubal(KDM)方法计算BA。心血管和血糖生物标志物与BA增加有关，而高强度的血压和血糖管理降低了BA到CA的水平，表明加速的BA可以在T2D设置下恢复。
Biological age (BA) closely depicts age-related changes at a cellular level. Type 2diabetes mellitus(T2D) accelerates BA when calculated using clinical biomarkers, but there is a large spread in the magnitude of individuals’ age acceleration in T2D suggesting additional factors contributing to BA. Additionally, it is unknown whether BA can be changed with treatment. We hypothesized that potential determinants of the heterogeneous BA distribution in T2D could be due to differential tissue aging as reflected at the DNA methylation (DNAm) level, or biological variables and their respective therapeutic treatments. Publicly available DNAm samples were obtained to calculate BA using the DNAm phenotypic age (DNAmPhenoAge) algorithm. DNAmPhenoAge showed age acceleration in T2D samples of whole blood, pancreatic islets, and liver, but not in adipose tissue or skeletal muscle. Analysis of genes associated with differentially methylated CpG sites found a significant correlation between eight individual CpG methylation sites and gene expression. Clinical biomarkers from participants in the NHANES 2017–2018 and ACCORD cohorts were used to calculate BA using the Klemera and Doubal (KDM) method. Cardiovascular and glycemic biomarkers associated with increased BA while intensive blood pressure and glycemic management reduced BA to CA levels, demonstrating that accelerated BA can be restored in the setting of T2D.