Limited evidence exists on the link between inflammation and epigenetic ageing. We aimed to 1) assess the cross-sectional and prospective associations of 22 inflammation-related plasma markers and a signature of inflammaging with epigenetic ageing; 2) determine whether epigenetic ageing and inflammaging are independently associated with mortality. Blood samples from 940 participants in the Melbourne Collaborative Cohort Study, collected at baseline (1990-1994) and follow-up (2003-2007) were assayed for DNA methylation and 22 inflammation-related markers, including well-established markers (e.g., interleukins and C-reactive protein) and metabolites of the tryptophan-kynurenine pathway. Four measures of epigenetic ageing (PhenoAge, GrimAge, DunedinPoAm and Zhang) and a signature of inflammaging were considered, adjusted for age, and transformed to Z-scores. Associations were assessed using linear regression, and mortality hazard ratios (HR) and 95% confidence intervals (95%CI) were estimated using Cox regression. Cross-sectionally, most inflammation-related markers were associated with epigenetic ageing measures, although with generally modest effect sizes (regression coefficients per SD≤0.26) and explaining altogether between 1% and 11% of their variation. Prospectively, baseline inflammation-related markers were not, or only weakly, associated with epigenetic ageing after 11 years of follow-up. Epigenetic ageing and inflammaging were strongly and independently associated with mortality, e.g. inflammaging: HR=1.41, 95%CI=1.27-1.56, P=2x10-10; which was only slightly attenuated after adjustment for four epigenetic ageing measures: HR=1.35, 95%CI=1.22-1.51, P=7x10-9). Although cross-sectionally associated with epigenetic ageing, inflammation-related markers accounted for a modest proportion of its variation. Inflammaging and epigenetic ageing are essentially non-overlapping markers of biological ageing and may be used jointly to predict mortality.

中文翻译：

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炎症和表观遗传衰老在很大程度上是生物衰老和死亡率的独立标志


关于炎症与表观遗传衰老之间联系的证据有限。我们的目的是 1) 评估 22 种炎症相关血浆标记物以及炎症特征与表观遗传衰老的横向和前瞻性关联； 2）确定表观遗传衰老和炎症是否与死亡率独立相关。墨尔本合作队列研究的 940 名参与者在基线（1990-1994 年）和随访（2003-2007 年）收集的血液样本进行了 DNA 甲基化和 22 种炎症相关标记物的检测，包括成熟的标记物（例如白细胞介素）和 C 反应蛋白）以及色氨酸-犬尿氨酸途径的代谢物。考虑了四种表观遗传衰老指标（PhenoAge、GrimAge、DunedinPoAm 和Zhang）和炎症特征，根据年龄进行调整，并转换为 Z 分数。使用线性回归评估相关性，并使用 Cox 回归评估死亡率风险比 (HR) 和 95% 置信区间 (95%CI)。从横截面来看，大多数炎症相关标志物与表观遗传衰老指标相关，尽管效应大小通常不大（每 SD 的回归系数≤0.26），并且可以解释 1% 到 11% 的变异。前瞻性地，在 11 年的随访后，基线炎症相关标志物与表观遗传衰老没有或只有微弱的相关性。表观遗传衰老和炎症与死亡率密切且独立相关，例如炎症：HR=1.41，95%CI=1.27-1.56，P=2x10-10；在调整四种表观遗传衰老指标后仅略有减弱：HR=1.35，95%CI=1.22-1.51，P=7x10-9）。 尽管与表观遗传衰老相关，但炎症相关标记物在其变异中所占比例不大。炎症和表观遗传衰老本质上是生物衰老的不重叠标志，可以联合用于预测死亡率。