Identification, replication and characterization of epigenetic remodelling in the aging genome: a cross population analysis

Abstract Aging is a complex biological process regulated by multiple cellular pathways and molecular mechanisms including epigenetics. Using genome-wide DNA methylation data measured in a large collection of Scottish old individuals, we performed discovery association analysis to identify age-methyl...

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Autores principales:	Shuxia Li, Lene Christiansen, Kaare Christensen, Torben A. Kruse, Paul Redmond, Riccardo E. Marioni, Ian J. Deary, Qihua Tan
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b1bb2d7ea93c4e6193b7d93d4213dc62
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spelling	oai:doaj.org-article:b1bb2d7ea93c4e6193b7d93d4213dc622021-12-02T15:05:43ZIdentification, replication and characterization of epigenetic remodelling in the aging genome: a cross population analysis10.1038/s41598-017-08346-72045-2322https://doaj.org/article/b1bb2d7ea93c4e6193b7d93d4213dc622017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08346-7https://doaj.org/toc/2045-2322Abstract Aging is a complex biological process regulated by multiple cellular pathways and molecular mechanisms including epigenetics. Using genome-wide DNA methylation data measured in a large collection of Scottish old individuals, we performed discovery association analysis to identify age-methylated CpGs and replicated them in two independent Danish cohorts. The double-replicated CpGs were characterized by distribution over gene regions and location in relation to CpG islands. The replicated CpGs were further characterized by involvement in biological pathways to study their functional implications in aging. We identified 67,604 age-associated CpG sites reaching genome-wide significance of FWER <0.05, 86% demethylated with increasing age. Double-replication resulted in 5,168 CpGs (39% age-methylated and 61% age-demethylated) which were characterized by high concentration of age-methylated CpGs at 1stExon and TSS200 and a dominant pattern of age-demethylated CpGs at other gene regions, and by overwhelming age-related methylation in CpG islands and demethylation at shore/shelf and open sea. The differential distribution patterns over gene regions for methylated and demethylated CpGs both relate to reduced gene activity during aging. Pathway analysis showed that age-dependent methylations were especially involved in cellular signalling activities while demethylations particularly linked to functions of the extracellular matrix, all implicated in the aging process and age-related disease risk.Shuxia LiLene ChristiansenKaare ChristensenTorben A. KrusePaul RedmondRiccardo E. MarioniIan J. DearyQihua TanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-8 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Shuxia Li Lene Christiansen Kaare Christensen Torben A. Kruse Paul Redmond Riccardo E. Marioni Ian J. Deary Qihua Tan Identification, replication and characterization of epigenetic remodelling in the aging genome: a cross population analysis
description	Abstract Aging is a complex biological process regulated by multiple cellular pathways and molecular mechanisms including epigenetics. Using genome-wide DNA methylation data measured in a large collection of Scottish old individuals, we performed discovery association analysis to identify age-methylated CpGs and replicated them in two independent Danish cohorts. The double-replicated CpGs were characterized by distribution over gene regions and location in relation to CpG islands. The replicated CpGs were further characterized by involvement in biological pathways to study their functional implications in aging. We identified 67,604 age-associated CpG sites reaching genome-wide significance of FWER <0.05, 86% demethylated with increasing age. Double-replication resulted in 5,168 CpGs (39% age-methylated and 61% age-demethylated) which were characterized by high concentration of age-methylated CpGs at 1stExon and TSS200 and a dominant pattern of age-demethylated CpGs at other gene regions, and by overwhelming age-related methylation in CpG islands and demethylation at shore/shelf and open sea. The differential distribution patterns over gene regions for methylated and demethylated CpGs both relate to reduced gene activity during aging. Pathway analysis showed that age-dependent methylations were especially involved in cellular signalling activities while demethylations particularly linked to functions of the extracellular matrix, all implicated in the aging process and age-related disease risk.
format	article
author	Shuxia Li Lene Christiansen Kaare Christensen Torben A. Kruse Paul Redmond Riccardo E. Marioni Ian J. Deary Qihua Tan
author_facet	Shuxia Li Lene Christiansen Kaare Christensen Torben A. Kruse Paul Redmond Riccardo E. Marioni Ian J. Deary Qihua Tan
author_sort	Shuxia Li
title	Identification, replication and characterization of epigenetic remodelling in the aging genome: a cross population analysis
title_short	Identification, replication and characterization of epigenetic remodelling in the aging genome: a cross population analysis
title_full	Identification, replication and characterization of epigenetic remodelling in the aging genome: a cross population analysis
title_fullStr	Identification, replication and characterization of epigenetic remodelling in the aging genome: a cross population analysis
title_full_unstemmed	Identification, replication and characterization of epigenetic remodelling in the aging genome: a cross population analysis
title_sort	identification, replication and characterization of epigenetic remodelling in the aging genome: a cross population analysis
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/b1bb2d7ea93c4e6193b7d93d4213dc62
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Identification, replication and characterization of epigenetic remodelling in the aging genome: a cross population analysis

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