A genome-wide scan reveals important roles of DNA methylation in human longevity by regulating age-related disease genes

PloS One
Fu-Hui XiaoQing-Peng Kong

Abstract

It is recognized that genetic factors contribute to human longevity. Besides the hypothesis of existence of longevity genes, another suggests that a lower frequency of risk alleles decreases the incidence of age-related diseases in the long-lived people. However, the latter finds no support from recent genetic studies. Considering the crucial role of epigenetic modification in gene regulation, we then hypothesize that suppressing disease-related genes in longevity individuals is likely achieved by epigenetic modification, e.g. DNA methylation. To test this hypothesis, we investigated the genome-wide methylation profile in 4 Chinese female centenarians and 4 middle-aged controls using methyl-DNA immunoprecipitation sequencing. 626 differentially methylated regions (DMRs) were observed between both groups. Interestingly, genes with these DMRs were enriched in age-related diseases, including type-2 diabetes, cardiovascular disease, stroke and Alzheimer's disease. This pattern remains rather stable after including methylomes of two white individuals. Further analyses suggest that the observed DMRs likely have functional roles in regulating disease-associated gene expressions, with some genes [e.g. caspase 3 (CASP3)] being down-regu...Continue Reading

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Citations

Apr 2, 2016·Briefings in Functional Genomics·Fu-Hui XiaoYong-Han He
Jun 13, 2015·Oxidative Medicine and Cellular Longevity·Kenneth Maiese
May 5, 2016·Briefings in Functional Genomics·Liyuan HanYonghan He
Jan 1, 2015·Journal of Experimental Neuroscience·Katie L Pennington, Margaret M DeAngelis
Jan 27, 2018·Journal of Human Genetics·Yvonne ShaoLynn M Bekris
Mar 12, 2020·Human Molecular Genetics·Silke SzymczakAlmut Nebel
Mar 6, 2019·Frontiers in Genetics·Fu-Hui XiaoQing-Peng Kong
Sep 12, 2019·BMC Genomics·Rick J JansenBrandon L Pierce
Jul 30, 2017·International Journal of Environmental Research and Public Health·Jian QinZhiyong Zhang
Feb 1, 2021·Briefings in Bioinformatics·Jianjun JiangQingpeng Kong

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Datasets Mentioned

BETA
GSM774849
GSM848927

Methods Mentioned

BETA
immunoprecipitation
MeDIP-Seq
WGBS

Software Mentioned

Protein Analysis Through Evolutionary Relationships ( PANTHER ...
SOAPaligner
edgeR
Ensembl
GeneCards

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