Comprehensive longitudinal study of epigenetic mutations in aging

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.

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Cancer och onkologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Cancer and Oncology hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Medicinsk genetik hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Medical Genetics hsv//eng
Aging
Cancer
Epigenetic mutation
Twin study
adult
article
artifact
B lymphocyte
cancer diagnosis
epigenetics
female
genetic background
human
human cell
human experiment
human tissue
longitudinal study
major clinical study
male
methylation
pyrosequencing
stochastic model

Karlsson, RobertKarolinska Institutet (författare)
Jylhävä, JuuliaKarolinska Institutet (författare)
Hedman, Åsa K.Karolinska Institutet (författare)
Almqvist, CatarinaKarolinska Institutet (författare)
Karlsson, Ida K.Karolinska Institutet,Jönköping University,HHJ, Institutet för gerontologi,HHJ. ARN-J (Aging Research Network - Jönköping),Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden(Swepub:hj)karida (författare)
Pedersen, Nancy L.Karolinska Institutet (författare)
Almgren, MalinDepartment of Clinical Neuroscience, Centrum for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden (författare)
Hägg, SaraKarolinska Institutet (författare)
Karolinska InstitutetHHJ, Institutet för gerontologi (creator_code:org_t)

Av författaren/redakt...: Wang, Yunzhang; Karlsson, Robert; Jylhävä, Juulia; Hedman, Åsa K.; Almqvist, Catari ...; Karlsson, Ida K.; visa fler...; Pedersen, Nancy ...; Almgren, Malin; Hägg, Sara; visa färre...

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Cancer och onkol ...

MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Medicinska och f ...; och Medicinsk geneti ...

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