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Clin Epigenetics. 2019 Dec 9;11(1):187. doi: 10.1186/s13148-019-0788-9.

Comprehensive longitudinal study of epigenetic mutations in aging.

Author information

1
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Nobels väg 12A, 17177, Stockholm, Sweden.
2
Rheumatology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
3
Pfizer Worldwide Research and Development, Stockholm, Sweden.
4
Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
5
Institute of Gerontology and Aging Research Network - Jönköping (ARN-J), School of Health and Welfare, Jönköping University, Jönköping, Sweden.
6
Department of Clinical Neuroscience, Centrum for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
7
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Nobels väg 12A, 17177, Stockholm, Sweden. sara.hagg@ki.se.

Abstract

BACKGROUND:

The role of DNA methylation in aging has been widely studied. However, epigenetic mutations, here defined as aberrant methylation levels compared to the distribution in a population, are less understood. Hence, we investigated longitudinal accumulation of epigenetic mutations, using 994 blood samples collected at up to five time points from 375 individuals in old ages.

RESULTS:

We verified earlier cross-sectional evidence on the increase of epigenetic mutations with age, and identified important contributing factors including sex, CD19+ B cells, genetic background, cancer diagnosis, and technical artifacts. We further classified epigenetic mutations into High/Low Methylation Outliers (HMO/LMO) according to their changes in methylation, and specifically studied methylation sites (CpGs) that were prone to mutate (frequently mutated CpGs). We validated four epigenetically mutated CpGs using pyrosequencing in 93 samples. Furthermore, by using twins, we concluded that the age-related accumulation of epigenetic mutations was not related to genetic factors, hence driven by stochastic or environmental effects.

CONCLUSIONS:

Here we conducted a comprehensive study of epigenetic mutation and highlighted its important role in aging process and cancer development.

KEYWORDS:

Aging; Cancer; Epigenetic mutation; Twin study

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