Epigenetic mutation load is weakly correlated with epigenetic age acceleration.
Epigenetic mutation load is weakly correlated with epigenetic age acceleration.
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DOI：
10.18632/aging.103950
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发表时间：
2020-09-29
期刊：
影响因子：
--
通讯作者：
Ritz B
中科院分区：
文献类型：
--
作者：
Yan Q;Paul KC;Lu AT;Kusters C;Binder AM;Horvath S;Ritz B
DNA甲基化（DNAm）年龄估计被广泛用于研究与衰老相关的疾病。目前尚不清楚dna年龄是否与随机表观遗传突变（SEMs）的积累有关，SEMs反映了表观遗传维持系统的功能障碍。在这里，我们将表观遗传突变负荷（EML）定义为每个个体的sem总数。我们在四项基于人群的研究（总n = 6,388）中使用双权重中相关评估了EML和DNAm年龄加速估计值之间的关联。EML不仅与实足年龄呈正相关（meta r = 0.171），而且与Horvath泛组织时钟、内在表观遗传年龄加速、Hannum时钟和GrimAge时钟4项表观遗传年龄加速指标呈正相关（meta分析相关r = 0.109 ~ 0.179）。我们进一步对每个参与者的SEMs进行通路富集分析。富集结果证明了表观遗传突变的随机性，同时暗示了信号通路、神经发生通路、神经递质通路、糖皮质激素通路和昼夜节律通路可能有助于加速dna的衰老。最后，研究基因组区域特异性EML，我们发现位于转录抑制区域（TSS1500， TSS200和1stExon）的EML与更快的年龄加速相关。总的来说，我们的发现表明表观遗传突变的积累在衰老过程中的作用。
DNA methylation (DNAm) age estimators are widely used to study aging-related conditions. It is not yet known whether DNAm age is associated with the accumulation of stochastic epigenetic mutations (SEMs), which reflect dysfunctions of the epigenetic maintenance system. Here, we defined epigenetic mutation load (EML) as the total number of SEMs per individual. We assessed associations between EML and DNAm age acceleration estimators using biweight midcorrelations in four population-based studies (total n = 6,388). EML was not only positively associated with chronological age (meta r = 0.171), but also with four measures of epigenetic age acceleration: the Horvath pan tissue clock, intrinsic epigenetic age acceleration, the Hannum clock, and the GrimAge clock (meta-analysis correlation ranging from r = 0.109 to 0.179). We further conducted pathway enrichment analyses for each participant’s SEMs. The enrichment result demonstrated the stochasticity of epigenetic mutations, meanwhile implicated several pathways: signaling, neurogenesis, neurotransmitter, glucocorticoid, and circadian rhythm pathways may contribute to faster DNAm age acceleration. Finally, investigating genomic-region specific EML, we found that EMLs located within regions of transcriptional repression (TSS1500, TSS200, and 1stExon) were associated with faster age acceleration. Overall, our findings suggest a role for the accumulation of epigenetic mutations in the aging process.
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影响因子：
--
作者：
Gentilini D;Scala S;Gaudenzi G;Garagnani P;Capri M;Cescon M;Grazi GL;Bacalini MG;Pisoni S;Dicitore A;Circelli L;Santagata S;Izzo F;Di Blasio AM;Persani L;Franceschi C;Vitale G
通讯作者：
Vitale G
DOI：
10.1093/infdis/jiv277
发表时间：
2015-11-15
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Horvath S;Levine AJ
通讯作者：
Levine AJ
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：
5.6
作者：
Anderson, GL;Manson, J;Prentice, RL
通讯作者：
Prentice, RL
影响因子：
8.8
作者：
Breeze CE;Paul DS;van Dongen J;Butcher LM;Ambrose JC;Barrett JE;Lowe R;Rakyan VK;Iotchkova V;Frontini M;Downes K;Ouwehand WH;Laperle J;Jacques PÉ;Bourque G;Bergmann AK;Siebert R;Vellenga E;Saeed S;Matarese F;Martens JHA;Stunnenberg HG;Teschendorff AE;Herrero J;Birney E;Dunham I;Beck S
通讯作者：
Beck S