Cell and tissue type independent age-associated DNA methylation changes are not rare but common

Abstract

Age-associated DNA methylation changes have been widely reported across many different tissue and cell types. Epigenetic clocks that can predict chronological age with a surprisingly high degree of accuracy appear to do so independently of tissue and cell-type, suggesting that a component of epigenetic drift is cell-type independent. However, the relative amount of age-associated DNAm changes that are specific to a cell or tissue type versus the amount that occurs independently of cell or tissue type is unclear and a matter of debate, with a recent study concluding that most epigenetic drift is tissue-specific. Here, we perform a novel comprehensive statistical analysis, including matched multi cell-type and multi-tissue DNA methylation profiles from the same individuals and adjusting for cell-type heterogeneity, demonstrating that a substantial amount of epigenetic drift, possibly over 70%, is shared between significant numbers of different tissue/cell types. We further show that ELOVL2 is not unique and that many other CpG sites, some mapping to genes in the Wnt and glutamate receptor signaling pathways, are altered with age across at least 10 different cell/tissue types. We propose that while most age-associated DNAm changes are shared between cell-types that the putative functional effect is likely to be tissue-specific.