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Frailty is associated with the epigenetic clock but not with telomere length in a German cohort

BACKGROUND: The epigenetic clock, in particular epigenetic pre-aging quantified by the so-called DNA methylation age acceleration, has recently been suggested to closely correlate with a variety of disease phenotypes. There remains a dearth of data, however, on its association with telomere length a...

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Autores principales: Breitling, Lutz Philipp, Saum, Kai-Uwe, Perna, Laura, Schöttker, Ben, Holleczek, Bernd, Brenner, Hermann
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4768341/
https://www.ncbi.nlm.nih.gov/pubmed/26925173
http://dx.doi.org/10.1186/s13148-016-0186-5
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author Breitling, Lutz Philipp
Saum, Kai-Uwe
Perna, Laura
Schöttker, Ben
Holleczek, Bernd
Brenner, Hermann
author_facet Breitling, Lutz Philipp
Saum, Kai-Uwe
Perna, Laura
Schöttker, Ben
Holleczek, Bernd
Brenner, Hermann
author_sort Breitling, Lutz Philipp
collection PubMed
description BACKGROUND: The epigenetic clock, in particular epigenetic pre-aging quantified by the so-called DNA methylation age acceleration, has recently been suggested to closely correlate with a variety of disease phenotypes. There remains a dearth of data, however, on its association with telomere length and frailty, which can be considered major correlates of age on the genomic and clinical level, respectively. RESULTS: In this cross-sectional observational study on altogether 1820 subjects from two subsets (n = 969 and n = 851; mean ± standard deviation age 62.1 ± 6.5 and 63.0 ± 6.7 years, respectively) of the ESTHER cohort study of the elderly general population in Germany, DNA methylation age was calculated based on a 353 loci predictor previously developed in a large meta-study, and the difference-based epigenetic age acceleration was calculated as predicted methylation age minus chronological age. No correlation of epigenetic age acceleration with telomere length was found in our study (p = 0.63). However, there was an association of DNA methylation age acceleration with a comprehensive frailty measure, such that the accumulated deficits significantly increased with increasing age acceleration. Quantitatively, about half an additional deficit was added per 6 years of methylation age acceleration (p = 0.0004). This association was independent from age, sex, and estimated leukocyte distribution, as well as from a variety of other confounding variables considered. CONCLUSIONS: The results of the present study suggest that epigenetic age acceleration is correlated with clinically relevant aging-related phenotypes through pathways unrelated to cellular senescence as assessed by telomere length. Innovative approaches like Mendelian randomization will be needed to elucidate whether epigenetic age acceleration indeed plays a causal role for the development of clinical phenotypes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13148-016-0186-5) contains supplementary material, which is available to authorized users.
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spelling pubmed-47683412016-02-27 Frailty is associated with the epigenetic clock but not with telomere length in a German cohort Breitling, Lutz Philipp Saum, Kai-Uwe Perna, Laura Schöttker, Ben Holleczek, Bernd Brenner, Hermann Clin Epigenetics Research BACKGROUND: The epigenetic clock, in particular epigenetic pre-aging quantified by the so-called DNA methylation age acceleration, has recently been suggested to closely correlate with a variety of disease phenotypes. There remains a dearth of data, however, on its association with telomere length and frailty, which can be considered major correlates of age on the genomic and clinical level, respectively. RESULTS: In this cross-sectional observational study on altogether 1820 subjects from two subsets (n = 969 and n = 851; mean ± standard deviation age 62.1 ± 6.5 and 63.0 ± 6.7 years, respectively) of the ESTHER cohort study of the elderly general population in Germany, DNA methylation age was calculated based on a 353 loci predictor previously developed in a large meta-study, and the difference-based epigenetic age acceleration was calculated as predicted methylation age minus chronological age. No correlation of epigenetic age acceleration with telomere length was found in our study (p = 0.63). However, there was an association of DNA methylation age acceleration with a comprehensive frailty measure, such that the accumulated deficits significantly increased with increasing age acceleration. Quantitatively, about half an additional deficit was added per 6 years of methylation age acceleration (p = 0.0004). This association was independent from age, sex, and estimated leukocyte distribution, as well as from a variety of other confounding variables considered. CONCLUSIONS: The results of the present study suggest that epigenetic age acceleration is correlated with clinically relevant aging-related phenotypes through pathways unrelated to cellular senescence as assessed by telomere length. Innovative approaches like Mendelian randomization will be needed to elucidate whether epigenetic age acceleration indeed plays a causal role for the development of clinical phenotypes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13148-016-0186-5) contains supplementary material, which is available to authorized users. BioMed Central 2016-02-26 /pmc/articles/PMC4768341/ /pubmed/26925173 http://dx.doi.org/10.1186/s13148-016-0186-5 Text en © Breitling et al. 2016 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 Research
Breitling, Lutz Philipp
Saum, Kai-Uwe
Perna, Laura
Schöttker, Ben
Holleczek, Bernd
Brenner, Hermann
Frailty is associated with the epigenetic clock but not with telomere length in a German cohort
title Frailty is associated with the epigenetic clock but not with telomere length in a German cohort
title_full Frailty is associated with the epigenetic clock but not with telomere length in a German cohort
title_fullStr Frailty is associated with the epigenetic clock but not with telomere length in a German cohort
title_full_unstemmed Frailty is associated with the epigenetic clock but not with telomere length in a German cohort
title_short Frailty is associated with the epigenetic clock but not with telomere length in a German cohort
title_sort frailty is associated with the epigenetic clock but not with telomere length in a german cohort
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4768341/
https://www.ncbi.nlm.nih.gov/pubmed/26925173
http://dx.doi.org/10.1186/s13148-016-0186-5
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