The inactive X chromosome accumulates widespread epigenetic variability with age.

"availability of data and materials the bios whole blood samples are available from the european genome-phenome archive (egac00001000277).; all external datasets used in this study are publicly available from gene expression omnibus (geo) under accession numbers gse87571 [ 32 ] and gse56046 [ 33 ]. availability of data and materials the bios whole blood samples are available from the european genome-phenome archive (egac00001000277"

"scripts for the analyses in this manuscript are available at github [ https://github com/yunfenglumc/epigenetic_variability_chrx ] under an open source mit license."

"Declarations Ethics approval and consent to participateThe study was approved by the institutional review boards of the participating centers (CODAM, Medical Ethical Committee of the Maastricht University; LL, Ethics Committee of the University Medical Centre Groningen; LLS, Ethical Committee of the Leiden University Medical Center; PAN, Institutional Review Board of the University Medical Centre Utrecht; NTR, Central Ethics Committee on Research Involving Human Subjects of the VU University Medical Centre; RS, Institutional Review Board (Medical Ethics Committee) of the Erasmus Medical Center). All participants have given written informed consent, and the experimental methods comply with the Helsinki Declaration. Competing interestsThe authors declare that they have no competing interests. Competing interests The authors declare that they have no competing interests."

"Funding This work was financially supported by BBMRI-NL, a Research Infrastructure financed by the Dutch government (NWO, numbers 184.021.007 and 184.033.111). YL is supported by PhD fellowship from the China Scholarship Council (CSC)."