Low-level chronic inflammation increases with age and is associated with cognitive decline. DNA methylation (DNAm) levels may provide more stable reflections of cumulative inflammatory burden than traditional serum approaches. Using structural and diffusion MRI data from 521 individuals aged 73, we demonstrate that a DNAm proxy of C-Reactive Protein (CRP) shows significantly (on average 6.4-fold) stronger associations with brain structural outcomes than serum CRP. We additionally find that DNAm CRP has an inverse association with global and domain-specific (speed, visuospatial and memory) cognitive functioning, and that brain structure partially mediates this CRP-cognitive association (up to 29.4%), dependent on lifestyle and health factors. These data support the hypothesis that chronic systemic inflammation may contribute to neurodegenerative brain changes which underlie differences in cognitive ability in later life. DNA methylation-based predictors could be used as proxies for chronic inflammatory status.

中文翻译：

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作为慢性衰老的生物标志物，慢性炎症的表观遗传学表现优于血清水平

轻度慢性炎症随年龄增长而增加，并与认知能力下降有关。与传统的血清方法相比，DNA甲基化（DNAm）的水平可以提供更稳定的累积炎症负担反映。使用来自521个73岁的521个人的结构和扩散MRI数据，我们证明了C-反应蛋白（CRP）的DNAm代理比血清CRP显着（平均6.4倍）与脑结构结局的关联更强。我们还发现，DNAm CRP与全局和特定域（速度，视觉空间和记忆）认知功能呈负相关，并且大脑结构部分依赖于生活方式和健康因素介导了这种CRP认知关联（高达29.4％）。 。这些数据支持以下假设：慢性全身性炎症可能导致大脑神经退行性变化，这是以后生活中认知能力差异的基础。基于DNA甲基化的预测因子可以用作慢性炎症状态的代理。