PMID: 26342808Sep 8, 2015Paper

Stochastic epigenetic mutations (DNA methylation) increase exponentially in human aging and correlate with X chromosome inactivation skewing in females

Aging
Davide GentiliniAnna Maria Di Blasio

Abstract

In this study we applied a new analytical strategy to investigate the relations between stochastic epigenetic mutations (SEMs) and aging. We analysed methylation levels through the Infinium HumanMethylation27 and HumanMethylation450 BeadChips in a population of 178 subjects ranging from 3 to 106 years. For each CpG probe, epimutated subjects were identified as the extreme outliers with methylation level exceeding three times interquartile ranges the first quartile (Q1-(3 x IQR)) or the third quartile (Q3+(3 x IQR)). We demonstrated that the number of SEMs was low in childhood and increased exponentially during aging. Using the HUMARA method, skewing of X chromosome inactivation (XCI) was evaluated in heterozygotes women. Multivariate analysis indicated a significant correlation between log(SEMs) and degree of XCI skewing after adjustment for age (β = 0.41; confidence interval: 0.14, 0.68; p-value = 0.0053). The PATH analysis tested the complete model containing the variables: skewing of XCI, age, log(SEMs) and overall CpG methylation. After adjusting for the number of epimutations we failed to confirm the well reported correlation between skewing of XCI and aging. This evidence might suggest that the known correlation between X...Continue Reading

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Citations

Sep 20, 2017·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Eduardo Fernandez-RebolloWolfgang Wagner
Apr 27, 2019·International Journal of Molecular Sciences·Noémie GensousMaria Giulia Bacalini
Jul 28, 2020·International Journal of Molecular Sciences·Elena SpadaDavide Gentilini
Apr 2, 2016·Briefings in Functional Genomics·Fu-Hui XiaoYong-Han He
Mar 30, 2017·Biogerontology·Noémie GensousPaolo Garagnani
May 6, 2019·Clinical and Translational Medicine·Tan Boon TohEdward Kai-Hua Chow
Dec 11, 2019·Clinical Epigenetics·Yunzhang WangSara Hägg
Jun 13, 2018·Molecular Psychiatry·James H ColeIan J Deary
Dec 8, 2019·Aging Clinical and Experimental Research·Christina PagiatakisRoberto Papait
Jun 1, 2020·Human Reproduction·K W OlsenM L Grøndahl
Apr 18, 2018·Frontiers in Medicine·Claudio FranceschiStefano Salvioli
Oct 6, 2020·Frontiers in Plant Science·Moumouni KonateCarlos Marcelino Rodriguez Lopez
Aug 14, 2020·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Amedeo GagliardiGiovanni Fiorito
Dec 29, 2020·Frontiers in Neurology·Angela PeronMaria Paola Canevini
Jul 4, 2020·Environment International·Paolo VineisSonia Dagnino
Feb 4, 2021·International Journal of Molecular Sciences·Valentina GuidaDavide Gentilini

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