表观遗传学
德纳姆
生物
疾病
生物标志物发现
DNA甲基化
生物信息学
计算生物学
健康衰老
老化
衰老
生物标志物
医学
老年学
表观基因组
遗传学
蛋白质组学
内科学
基因
基因表达
作者
Morgan E. Levine,Ake T. Lu,Austin Quach,Brian H. Chen,Themistocles L. Assimes,Stefania Bandinelli,Lifang Hou,Andrea A. Baccarelli,James D. Stewart,Yun Li,Eric A. Whitsel,James G. Wilson,Alex P. Reiner,Abraham Aviv,Kurt Lohman,Yongmei Liu,Luigi Ferrucci,Steve Horvath
出处
期刊:Aging
[Impact Journals, LLC]
日期:2018-04-18
卷期号:10 (4): 573-591
被引量:1387
标识
DOI:10.18632/aging.101414
摘要
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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