Aging of blood can be tracked by DNA methylation changes at just three CpG sites
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- 作者：Carola Ingrid Weidner (17)
Qiong Lin (10)
Carmen Maike Koch (17)
Lewin Eisele (11)
Fabian Beier (12)
Patrick Ziegler (12)
Dirk Olaf Bauerschlag (13)
Karl-Heinz J?ckel (11)
Raimund Erbel (14)
Thomas Walter Mühleisen (15) (16) (17)
Martin Zenke (10)
Tim Henrik Brümmendorf (12)
Wolfgang Wagner (17) - 刊名：Genome Biology
- 出版年：2014
- 出版时间：February 2014
- 年：2014
- 卷：15
- 期：2
- 全文大小：1,054 KB
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Qiong Lin (10)
Carmen Maike Koch (17)
Lewin Eisele (11)
Fabian Beier (12)
Patrick Ziegler (12)
Dirk Olaf Bauerschlag (13)
Karl-Heinz J?ckel (11)
Raimund Erbel (14)
Thomas Walter Mühleisen (15) (16) (17)
Martin Zenke (10)
Tim Henrik Brümmendorf (12)
Wolfgang Wagner (17)
17. Institute of Neuroscience and Medicine (INM-1), Research Center Juelich, Juelich, Germany
10. Institute for Biomedical Engineering - Cell Biology, RWTH Aachen University Medical School, Aachen, Germany
11. Institute for Medical Informatics, Biometry and Epidemiology, University Duisburg-Essen, Essen, Germany
12. Department of Oncology, Hematology and Stem Cell Transplantation, RWTH Aachen University Medical School, Aachen, Germany
13. Department of Obstetrics and Gynecology, RWTH Aachen University Medical School, Aachen, Germany
14. Department of Cardiology, West-German Heart Center Essen, University Duisburg-Essen, Essen, Germany
15. Institute of Human Genetics, University of Bonn, Bonn, Germany
16. Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany - ISSN：1465-6906
文摘
Background Human aging is associated with DNA methylation changes at specific sites in the genome. These epigenetic modifications may be used to track donor age for forensic analysis or to estimate biological age. Results We perform a comprehensive analysis of methylation profiles to narrow down 102 age-related CpG sites in blood. We demonstrate that most of these age-associated methylation changes are reversed in induced pluripotent stem cells (iPSCs). Methylation levels at three age-related CpGs - located in the genes ITGA2B, ASPA and PDE4C - were subsequently analyzed by bisulfite pyrosequencing of 151 blood samples. This epigenetic aging signature facilitates age predictions with a mean absolute deviation from chronological age of less than 5 years. This precision is higher than age predictions based on telomere length. Variation of age predictions correlates moderately with clinical and lifestyle parameters supporting the notion that age-associated methylation changes are associated more with biological age than with chronological age. Furthermore, patients with acquired aplastic anemia or dyskeratosis congenita - two diseases associated with progressive bone marrow failure and severe telomere attrition - are predicted to be prematurely aged. Conclusions Our epigenetic aging signature provides a simple biomarker to estimate the state of aging in blood. Age-associated DNA methylation changes are counteracted in iPSCs. On the other hand, over-estimation of chronological age in bone marrow failure syndromes is indicative for exhaustion of the hematopoietic cell pool. Thus, epigenetic changes upon aging seem to reflect biological aging of blood.