Cite this Article
How to cite
Gentilini D, Garagnani P, Pisoni S, Bacalini MG, Calzari L, Mari D, Vitale G, Franceschi C, Di Blasio AM, . Stochastic epigenetic mutations (DNA methylation) increase exponentially in human aging and correlate with X chromosome inactivation skewing in females. . 7:568-578. https://doi.org/10.18632/aging.100792
Copy or Download citation:
Select the format you require from the list below
Provider:
TY - JOUR
AU - Gentilini, Davide
AU - Garagnani, Paolo
AU - Pisoni, Serena
AU - Bacalini, Maria Giulia
AU - Calzari, Luciano
AU - Mari, Daniela
AU - Vitale, Giovanni
AU - Franceschi, Claudio
AU - Di Blasio, Anna Maria
TI - Stochastic epigenetic mutations (DNA methylation) increase exponentially in human aging and correlate with X chromosome inactivation skewing in females
JO -
JA -
VL - 7
IS - 8
PB -
SN -
UR - https://doi.org/10.18632/aging.100792
DO - 10.18632/aging.100792
SP - 568
EP - 578
PY -
AB - 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 × IQR)) or the third quartile (Q3+(3 × 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 XCI skewing and aging could not be a direct association but mediated by the number of SEMs
ER -
Click to copy this citation from the text box above or download the citation: