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

Weidner, Carola Ingrid, Lin, Qiong, Koch, Carmen Maike, Eisele, Lewin, Beier, Fabian, Ziegler, Patrick, Bauerschlag, Dirk Olaf, Jöckel, Karl-Heinz, Erbel, Raimund, Mühleisen, Thomas Walter, Zenke, Martin, Brümmendorf, Tim Henrik, Wagner, Wolfgang·2014·Genome Biology
DOI 10.1186/gb-2014-15-2-r24PMC PMC4053864
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Abstract

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.

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Metadata

Authors
Weidner, C. I., Lin, Q., Koch, C. M., Eisele, L., Beier, F., Ziegler, P., Bauerschlag, D. O., Jöckel, K.-H., Erbel, R., Mühleisen, T. W., Zenke, M., Brümmendorf, T. H., & Wagner, W.
Venue
Genome Biology
Publisher
Springer Science and Business Media LLC
Published
2014-02-03
Volume
15
Issue
2
ISSN
1474-760X
DOI
10.1186/gb-2014-15-2-r24
PMC
PMC4053864
Cited by
837
References
10
Language
en
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