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Individual CpG sites that are associated with age and life expectancy become hypomethylated upon aging

BACKGROUND: There is a growing interest in simple molecular biomarkers for biological aging. Age-associated DNA methylation (DNAm) changes at specific CG dinucleotides can be combined into epigenetic age predictors to estimate chronological age—and the deviation of chronological and predicted age (∆...

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Autores principales: Zhang, Yan, Hapala, Jan, Brenner, Hermann, Wagner, Wolfgang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5288846/
https://www.ncbi.nlm.nih.gov/pubmed/28168006
http://dx.doi.org/10.1186/s13148-017-0315-9
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author Zhang, Yan
Hapala, Jan
Brenner, Hermann
Wagner, Wolfgang
author_facet Zhang, Yan
Hapala, Jan
Brenner, Hermann
Wagner, Wolfgang
author_sort Zhang, Yan
collection PubMed
description BACKGROUND: There is a growing interest in simple molecular biomarkers for biological aging. Age-associated DNA methylation (DNAm) changes at specific CG dinucleotides can be combined into epigenetic age predictors to estimate chronological age—and the deviation of chronological and predicted age (∆(age)) seems to be associated with all-cause mortality. In this study, we have further validated this association and analyzed whether or not individual age-associated CG-dinucleotides (CpGs) are related to life expectancy. FINDINGS: In the German ESTHER cohort, we used 864 DNAm profiles of blood samples as the discovery set and 1000 DNAm profiles as the validation set to predict chronological age with three previously reported age predictors—based on 99, 71, or 353 age-associated CpGs. Several of these individual CpGs were significantly associated with life expectancy, and for some of these CpGs, this was even reproducible in the independent datasets. Notably, those CpGs that revealed significant association with life expectancy were overall rather hypomethylated upon aging. CONCLUSION: Individual age-associated CpGs may provide biomarkers for all-cause mortality—but confounding factors need to be critically taken into consideration, and alternative methods, which facilitate more quantitative measurements at individual CpGs, might be advantageous. Our data suggest that particularly specific CpGs that become hypomethylated upon aging are indicative of biological aging. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13148-017-0315-9) contains supplementary material, which is available to authorized users.
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spelling pubmed-52888462017-02-06 Individual CpG sites that are associated with age and life expectancy become hypomethylated upon aging Zhang, Yan Hapala, Jan Brenner, Hermann Wagner, Wolfgang Clin Epigenetics Short Report BACKGROUND: There is a growing interest in simple molecular biomarkers for biological aging. Age-associated DNA methylation (DNAm) changes at specific CG dinucleotides can be combined into epigenetic age predictors to estimate chronological age—and the deviation of chronological and predicted age (∆(age)) seems to be associated with all-cause mortality. In this study, we have further validated this association and analyzed whether or not individual age-associated CG-dinucleotides (CpGs) are related to life expectancy. FINDINGS: In the German ESTHER cohort, we used 864 DNAm profiles of blood samples as the discovery set and 1000 DNAm profiles as the validation set to predict chronological age with three previously reported age predictors—based on 99, 71, or 353 age-associated CpGs. Several of these individual CpGs were significantly associated with life expectancy, and for some of these CpGs, this was even reproducible in the independent datasets. Notably, those CpGs that revealed significant association with life expectancy were overall rather hypomethylated upon aging. CONCLUSION: Individual age-associated CpGs may provide biomarkers for all-cause mortality—but confounding factors need to be critically taken into consideration, and alternative methods, which facilitate more quantitative measurements at individual CpGs, might be advantageous. Our data suggest that particularly specific CpGs that become hypomethylated upon aging are indicative of biological aging. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13148-017-0315-9) contains supplementary material, which is available to authorized users. BioMed Central 2017-02-02 /pmc/articles/PMC5288846/ /pubmed/28168006 http://dx.doi.org/10.1186/s13148-017-0315-9 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Short Report
Zhang, Yan
Hapala, Jan
Brenner, Hermann
Wagner, Wolfgang
Individual CpG sites that are associated with age and life expectancy become hypomethylated upon aging
title Individual CpG sites that are associated with age and life expectancy become hypomethylated upon aging
title_full Individual CpG sites that are associated with age and life expectancy become hypomethylated upon aging
title_fullStr Individual CpG sites that are associated with age and life expectancy become hypomethylated upon aging
title_full_unstemmed Individual CpG sites that are associated with age and life expectancy become hypomethylated upon aging
title_short Individual CpG sites that are associated with age and life expectancy become hypomethylated upon aging
title_sort individual cpg sites that are associated with age and life expectancy become hypomethylated upon aging
topic Short Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5288846/
https://www.ncbi.nlm.nih.gov/pubmed/28168006
http://dx.doi.org/10.1186/s13148-017-0315-9
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