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Aging of blood can be tracked by DNA methylation changes at just three CpG sites

Carola Ingrid Weidner1, Qiong Lin2, Carmen Maike Koch1, Lewin Eisele3, Fabian Beier4, Patrick Ziegler4, Dirk Olaf Bauerschlag5, Karl-Heinz Jöckel3, Raimund Erbel6, Thomas Walter Mühleisen789, Martin Zenke2, Tim Henrik Brümmendorf4 and Wolfgang Wagner1*

Author Affiliations

1 Helmholtz-Institute for Biomedical Engineering; Stem Cell Biology and Cellular Engineering, RWTH Aachen University Medical School, Aachen, Germany

2 Institute for Biomedical Engineering - Cell Biology, RWTH Aachen University Medical School, Aachen, Germany

3 Institute for Medical Informatics, Biometry and Epidemiology, University Duisburg-Essen, Essen, Germany

4 Department of Oncology, Hematology and Stem Cell Transplantation, RWTH Aachen University Medical School, Aachen, Germany

5 Department of Obstetrics and Gynecology, RWTH Aachen University Medical School, Aachen, Germany

6 Department of Cardiology, West-German Heart Center Essen, University Duisburg-Essen, Essen, Germany

7 Institute of Human Genetics, University of Bonn, Bonn, Germany

8 Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany

9 Institute of Neuroscience and Medicine (INM-1), Research Center Juelich, Juelich, Germany

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Genome Biology 2014, 15:R24  doi:10.1186/gb-2014-15-2-r24

Published: 3 February 2014



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.


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.


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.