An epigenetic biomarker of aging for lifespan and healthspan.
An epigenetic biomarker of aging for lifespan and healthspan.
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DOI：
10.18632/aging.101414
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发表时间：
2018-04-18
期刊：
影响因子：
--
通讯作者：
Horvath S
中科院分区：
文献类型：
--
作者：
Levine ME;Lu AT;Quach A;Chen BH;Assimes TL;Bandinelli S;Hou L;Baccarelli AA;Stewart JD;Li Y;Whitsel EA;Wilson JG;Reiner AP;Aviv A;Lohman K;Liu Y;Ferrucci L;Horvath S
确定可靠的衰老生物标志物是老年科学的主要目标。虽然第一代衰老的表观遗传生物标志物是使用实足年龄作为生物学年龄的替代物开发的，但我们假设，结合表型年龄的复合临床指标（捕获寿命和健康寿命的差异）可能会识别新的CpG，并促进开发更强大的衰老表观遗传生物标志物。使用创新的两步过程，我们开发了一种新的衰老表观遗传生物标志物DNAm PhenoAge，在预测各种衰老结果方面，包括全因死亡率，癌症，健康寿命，身体功能和阿尔茨海默病方面，它远远优于以前的措施。虽然这种生物标志物是使用全血数据开发的，但它与测试的每个组织和细胞的年龄密切相关。基于对分选细胞的深入转录分析，我们发现，相对于实际年龄，表观遗传的增加与促炎和干扰素途径的激活增加以及转录/翻译机制、DNA损伤反应和线粒体特征的激活减少有关。总体而言，这种衰老的单一表观遗传生物标志物能够捕获多种组织和细胞中一系列不同结果的风险，并提供对衰老重要途径的深入了解。
Identifying reliable biomarkers of aging is a major goal in geroscience. While the first generation of epigenetic biomarkers of aging were developed using chronological age as a surrogate for biological age, we hypothesized that incorporation of composite clinical measures of phenotypic age that capture differences in lifespan and healthspan may identify novel CpGs and facilitate the development of a more powerful epigenetic biomarker of aging. Using an innovative two-step process, we develop a new epigenetic biomarker of aging, DNAm PhenoAge, that strongly outperforms previous measures in regards to predictions for a variety of aging outcomes, including all-cause mortality, cancers, healthspan, physical functioning, and Alzheimer's disease. While this biomarker was developed using data from whole blood, it correlates strongly with age in every tissue and cell tested. Based on an in-depth transcriptional analysis in sorted cells, we find that increased epigenetic, relative to chronological age, is associated with increased activation of pro-inflammatory and interferon pathways, and decreased activation of transcriptional/translational machinery, DNA damage response, and mitochondrial signatures. Overall, this single epigenetic biomarker of aging is able to capture risks for an array of diverse outcomes across multiple tissues and cells, and provide insight into important pathways in aging.
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影响因子：
3.7
作者：
Bocklandt S;Lin W;Sehl ME;Sánchez FJ;Sinsheimer JS;Horvath S;Vilain E
通讯作者：
Vilain E
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：
12.3
作者：
Horvath S
通讯作者：
Horvath S
吸烟的表观遗传签名。
DOI：
10.1161/circgenetics.116.001506
发表时间：
2016-10
期刊：
Circulation. Cardiovascular genetics
影响因子：
--
作者：
Joehanes R;Just AC;Marioni RE;Pilling LC;Reynolds LM;Mandaviya PR;Guan W;Xu T;Elks CE;Aslibekyan S;Moreno-Macias H;Smith JA;Brody JA;Dhingra R;Yousefi P;Pankow JS;Kunze S;Shah SH;McRae AF;Lohman K;Sha J;Absher DM;Ferrucci L;Zhao W;Demerath EW;Bressler J;Grove ML;Huan T;Liu C;Mendelson MM;Yao C;Kiel DP;Peters A;Wang-Sattler R;Visscher PM;Wray NR;Starr JM;Ding J;Rodriguez CJ;Wareham NJ;Irvin MR;Zhi D;Barrdahl M;Vineis P;Ambatipudi S;Uitterlinden AG;Hofman A;Schwartz J;Colicino E;Hou L;Vokonas PS;Hernandez DG;Singleton AB;Bandinelli S;Turner ST;Ware EB;Smith AK;Klengel T;Binder EB;Psaty BM;Taylor KD;Gharib SA;Swenson BR;Liang L;DeMeo DL;O'Connor GT;Herceg Z;Ressler KJ;Conneely KN;Sotoodehnia N;Kardia SL;Melzer D;Baccarelli AA;van Meurs JB;Romieu I;Arnett DK;Ong KK;Liu Y;Waldenberger M;Deary IJ;Fornage M;Levy D;London SJ
通讯作者：
London SJ