A comparison of blood and brain-derived ageing and inflammation-related DNA methylation signatures and their association with microglial burdens.
A comparison of blood and brain-derived ageing and inflammation-related DNA methylation signatures and their association with microglial burdens.
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DOI：
10.1111/ejn.15661
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发表时间：
2022-11
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影响因子：
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血液中炎症和衰老相关的 DNA 甲基化模式与多种疾病有关，包括认知能力下降和神经退行性疾病。然而，目前尚不清楚这些基于血液的模式如何与大脑内的模式相关，以及每种模式如何与中央细胞特征相关。在这项研究中，我们对来自 1936 年洛锡安出生队列的 14 名个体的血液和五个死后大脑区域（BA17、BA20/21、BA24、BA46 和海马）的 DNA 甲基化进行了分析。还对相同大脑区域的小胶质细胞负荷进行了量化。跨组织和区域比较了五种表观遗传衰老生物标志物（“表观遗传时钟”）和两种炎症生物标志物（C 反应蛋白和白细胞介素 6 的甲基化代理）的 DNA 甲基化特征。根据评估的区域，血液和大脑中的炎症与衰老特征之间存在不同的关联。五个评估的表观遗传年龄加速指标中的四个被发现在海马体中最高（β范围 = 0.83–1.14，p ≤ 0.02）。与炎症相关的 DNA 甲基化特征在不同大脑区域没有显示出明显的差异。发现海马区的反应性小胶质细胞负荷最高（β = 1.32，p = 5 × 10−4）；然而，基于血液和大脑的甲基化特征与小胶质细胞之间唯一确定的关联是与所有五个大脑区域平均的一个表观遗传时钟（称为 DNAm PhenoAge）的加速呈显着正相关（β = 0.40，p = 0.002）。这项工作强调了海马体对表观遗传衰老的潜在脆弱性，并提供了大脑 DNA 甲基化特征与小胶质细胞负担差异之间关系的初步证据。对血液和五个死后大脑区域中的 DNA 甲基化进行了分析。对相同大脑区域的小胶质细胞负荷进行了量化。跨组织和区域比较了五种表观遗传衰老生物标志物（“表观遗传时钟”）和两种炎症生物标志物（CRP 和 IL-6 的甲基化代理）的 DNA 甲基化特征，以研究外周和中枢炎症和年龄相关甲基化模式之间的联系以及它们与中枢细胞谱的关系。
Inflammation and ageing‐related DNA methylation patterns in the blood have been linked to a variety of morbidities, including cognitive decline and neurodegenerative disease. However, it is unclear how these blood‐based patterns relate to patterns within the brain and how each associates with central cellular profiles. In this study, we profiled DNA methylation in both the blood and in five post mortem brain regions (BA17, BA20/21, BA24, BA46 and hippocampus) in 14 individuals from the Lothian Birth Cohort 1936. Microglial burdens were additionally quantified in the same brain regions. DNA methylation signatures of five epigenetic ageing biomarkers (‘epigenetic clocks’), and two inflammatory biomarkers (methylation proxies for C‐reactive protein and interleukin‐6) were compared across tissues and regions. Divergent associations between the inflammation and ageing signatures in the blood and brain were identified, depending on region assessed. Four out of the five assessed epigenetic age acceleration measures were found to be highest in the hippocampus (β range = 0.83–1.14, p ≤ 0.02). The inflammation‐related DNA methylation signatures showed no clear variation across brain regions. Reactive microglial burdens were found to be highest in the hippocampus (β = 1.32, p = 5 × 10−4); however, the only association identified between the blood‐ and brain‐based methylation signatures and microglia was a significant positive association with acceleration of one epigenetic clock (termed DNAm PhenoAge) averaged over all five brain regions (β = 0.40, p = 0.002). This work highlights a potential vulnerability of the hippocampus to epigenetic ageing and provides preliminary evidence of a relationship between DNA methylation signatures in the brain and differences in microglial burdens. DNA methylation was profiled in the blood and in five post mortem brain regions. Microglial burdens were quantified in the same brain regions. DNA methylation signatures of five epigenetic ageing biomarkers (‘epigenetic clocks’), and two inflammatory biomarkers (methylation proxies for CRP and IL‐6) were compared across tissues and regions to investigate the link between peripheral and central inflammation‐ and age‐related methylation patterns and how they relate to central cellular profiles.
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全基因组甲基化谱揭示了人类衰老速度的定量观点。
影响因子：
16
作者：
Hannum, Gregory;Guinney, Justin;Zhao, Ling;Zhang, Li;Hughes, Guy;Sadda, SriniVas;Klotzle, Brandy;Bibikova, Marina;Fan, Jian-Bing;Gao, Yuan;Deconde, Rob;Chen, Menzies;Rajapakse, Indika;Friend, Stephen;Ideker, Trey;Zhang, Kang
通讯作者：
Zhang, Kang
影响因子：
3.3
作者：
Barker ED;Cecil CAM;Walton E;Houtepen LC;O'Connor TG;Danese A;Jaffee SR;Jensen SKG;Pariante C;McArdle W;Gaunt TR;Relton CL;Roberts S
通讯作者：
Roberts S
影响因子：
4.1
作者：
Deary IJ;Gow AJ;Taylor MD;Corley J;Brett C;Wilson V;Campbell H;Whalley LJ;Visscher PM;Porteous DJ;Starr JM
通讯作者：
Starr JM
影响因子：
9.9
作者：
Beydoun, May A.;Shaked, Danielle;Zonderman, Alan B.
通讯作者：
Zonderman, Alan B.
影响因子：
12.3
作者：
Ligthart S;Marzi C;Aslibekyan S;Mendelson MM;Conneely KN;Tanaka T;Colicino E;Waite LL;Joehanes R;Guan W;Brody JA;Elks C;Marioni R;Jhun MA;Agha G;Bressler J;Ward-Caviness CK;Chen BH;Huan T;Bakulski K;Salfati EL;WHI-EMPC Investigators;Fiorito G;CHARGE epigenetics of Coronary Heart Disease;Wahl S;Schramm K;Sha J;Hernandez DG;Just AC;Smith JA;Sotoodehnia N;Pilling LC;Pankow JS;Tsao PS;Liu C;Zhao W;Guarrera S;Michopoulos VJ;Smith AK;Peters MJ;Melzer D;Vokonas P;Fornage M;Prokisch H;Bis JC;Chu AY;Herder C;Grallert H;Yao C;Shah S;McRae AF;Lin H;Horvath S;Fallin D;Hofman A;Wareham NJ;Wiggins KL;Feinberg AP;Starr JM;Visscher PM;Murabito JM;Kardia SL;Absher DM;Binder EB;Singleton AB;Bandinelli S;Peters A;Waldenberger M;Matullo G;Schwartz JD;Demerath EW;Uitterlinden AG;van Meurs JB;Franco OH;Chen YI;Levy D;Turner ST;Deary IJ;Ressler KJ;Dupuis J;Ferrucci L;Ong KK;Assimes TL;Boerwinkle E;Koenig W;Arnett DK;Baccarelli AA;Benjamin EJ;Dehghan A
通讯作者：
Dehghan A