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DNA methylation levels at individual age-associated CpG sites can be indicative for life expectancy

DNA-methylation (DNAm) levels at age-associated CpG sites can be combined into epigenetic aging signatures to estimate donor age. It has been demonstrated that the difference between such epigenetic age-predictions and chronological age is indicative for of all-cause mortality in later life. In this...

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Autores principales: Lin, Qiong, Weidner, Carola I., Costa, Ivan G., Marioni, Riccardo E., Ferreira, Marcelo R. P., Deary, Ian J., Wagner, Wolfgang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4789590/
https://www.ncbi.nlm.nih.gov/pubmed/26928272
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author Lin, Qiong
Weidner, Carola I.
Costa, Ivan G.
Marioni, Riccardo E.
Ferreira, Marcelo R. P.
Deary, Ian J.
Wagner, Wolfgang
author_facet Lin, Qiong
Weidner, Carola I.
Costa, Ivan G.
Marioni, Riccardo E.
Ferreira, Marcelo R. P.
Deary, Ian J.
Wagner, Wolfgang
author_sort Lin, Qiong
collection PubMed
description DNA-methylation (DNAm) levels at age-associated CpG sites can be combined into epigenetic aging signatures to estimate donor age. It has been demonstrated that the difference between such epigenetic age-predictions and chronological age is indicative for of all-cause mortality in later life. In this study, we tested alternative epigenetic signatures and followed the hypothesis that even individual age-associated CpG sites might be indicative for life-expectancy. Using a 99-CpG aging model, a five-year higher age-prediction was associated with 11% greater mortality risk in DNAm profiles of the Lothian Birth Cohort 1921 study. However, models based on three CpGs, or even individual CpGs, generally revealed very high offsets in age-predictions if applied to independent microarray datasets. On the other hand, we demonstrate that DNAm levels at several individual age-associated CpGs seem to be associated with life expectancy – e.g., at CpGs associated with the genes PDE4C and CLCN6. Our results support the notion that small aging signatures should rather be analysed by more quantitative methods, such as site-specific pyrosequencing, as the precision of age-predictions is rather low on independent microarray datasets. Nevertheless, the results hold the perspective that simple epigenetic biomarkers, based on few or individual age-associated CpGs, could assist the estimation of biological age.
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spelling pubmed-47895902016-03-28 DNA methylation levels at individual age-associated CpG sites can be indicative for life expectancy Lin, Qiong Weidner, Carola I. Costa, Ivan G. Marioni, Riccardo E. Ferreira, Marcelo R. P. Deary, Ian J. Wagner, Wolfgang Aging (Albany NY) Research Paper DNA-methylation (DNAm) levels at age-associated CpG sites can be combined into epigenetic aging signatures to estimate donor age. It has been demonstrated that the difference between such epigenetic age-predictions and chronological age is indicative for of all-cause mortality in later life. In this study, we tested alternative epigenetic signatures and followed the hypothesis that even individual age-associated CpG sites might be indicative for life-expectancy. Using a 99-CpG aging model, a five-year higher age-prediction was associated with 11% greater mortality risk in DNAm profiles of the Lothian Birth Cohort 1921 study. However, models based on three CpGs, or even individual CpGs, generally revealed very high offsets in age-predictions if applied to independent microarray datasets. On the other hand, we demonstrate that DNAm levels at several individual age-associated CpGs seem to be associated with life expectancy – e.g., at CpGs associated with the genes PDE4C and CLCN6. Our results support the notion that small aging signatures should rather be analysed by more quantitative methods, such as site-specific pyrosequencing, as the precision of age-predictions is rather low on independent microarray datasets. Nevertheless, the results hold the perspective that simple epigenetic biomarkers, based on few or individual age-associated CpGs, could assist the estimation of biological age. Impact Journals LLC 2016-02-25 /pmc/articles/PMC4789590/ /pubmed/26928272 Text en Copyright: © 2016 Lin et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Lin, Qiong
Weidner, Carola I.
Costa, Ivan G.
Marioni, Riccardo E.
Ferreira, Marcelo R. P.
Deary, Ian J.
Wagner, Wolfgang
DNA methylation levels at individual age-associated CpG sites can be indicative for life expectancy
title DNA methylation levels at individual age-associated CpG sites can be indicative for life expectancy
title_full DNA methylation levels at individual age-associated CpG sites can be indicative for life expectancy
title_fullStr DNA methylation levels at individual age-associated CpG sites can be indicative for life expectancy
title_full_unstemmed DNA methylation levels at individual age-associated CpG sites can be indicative for life expectancy
title_short DNA methylation levels at individual age-associated CpG sites can be indicative for life expectancy
title_sort dna methylation levels at individual age-associated cpg sites can be indicative for life expectancy
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4789590/
https://www.ncbi.nlm.nih.gov/pubmed/26928272
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