Alterations in 5hmC Level and Genomic Distribution in Aging-Related Epigenetic Drift in Human Adipose Stem Cells

Epigenomics. 2020 Mar;12(5):423-437. doi: 10.2217/epi-2019-0131. Epub 2020 Feb 7.

Abstract

Aim: To clarify mechanisms affecting the level and distribution of 5-hydroxymethylcytosine (5hmC) during aging. Materials & methods: We examined levels and genomic distribution of 5hmC along with the expression of ten-eleven translocation methylcytosine dioxygenases (TETs) in adipose stem cells in young and age-advanced individuals. Results: 5hmC levels were higher in adipose stem cells of age-advanced than young individuals (p = 0.0003), but were not associated with age-related changes in expression of TETs. 5hmC levels correlated with population doubling time (r = 0.62; p = 0.01). We identified 58 differentially hydroxymethylated regions. Hypo-hydroxymethylated differentially hydroxymethylated regions were approximately twofold enriched in CCCTC-binding factor binding sites. Conclusion: Accumulation of 5hmC in aged cells can result from inefficient active demethylation due to altered TETs activity and reduced passive demethylation due to slower proliferation.

Keywords: 5-hydroxymethylcytosine; 5hmC; ASC; CCCTC-binding factor; CTCF; DHMR; SAT; TET enzymes; adipose stem cell; aging; differentially hydroxymethylated regions; subcutaneous adipose tissue; ten–eleven translocation methylcytosine dioxygenase enzymes.