Age-related accrual of methylomic variability is linked to fundamental ageing mechanisms
- Slieker, R.C.
- van Iterson, M.
- Luijk, R.
- Beekman, M.
- Zhernakova, D.V.
- Moed, M.H.
- Mei, H.
- van Galen, M.
- Deelen, P.
- Bonder, M.J.
- Zhernakova, A.
- Uitterlinden, A.G.
- Tigchelaar, E.F.
- Stehouwer, C.D.A.
- Schalkwijk, C.G.
- van der Kallen, C.J.H.
- Hofman, A.
- van Heemst, D.
- de Geus, E.J.C.
- van Dongen, J.
- Deelen, J.
- Van den Berg, L.H.
- van Meurs, J.
- Jansen, R.
- 't Hoen, P.A.C.
- Franke, L.
- Wijmenga, C.
- Veldink, J.H.
- Swertz, M.A.
- van Greevenbroek, M.M.J.
- van Duijn, C.M.
- Boomsma, D.I.
- Slagboom, P.E.
- Heijmans, B.T.
DOIAbstract
Background: Epigenetic change is a hallmark of ageing but its link to ageing mechanisms in humans remains poorly understood. While DNA methylation at many CpG sites closely tracks chronological age, DNA methylation changes relevant to biological age are expected to gradually dissociate from chronological age, mirroring the increased heterogeneity in health status at older ages. Results: Here, we report on the large-scale identification of 6366 age-related variably methylated positions (aVMPs) identified in 3295 whole blood DNA methylation profiles, 2044 of which have a matching RNA-seq gene expression profile. aVMPs are enriched at polycomb repressed regions and, accordingly, methylation at those positions is associated with the expression ...
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