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

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
• adipose stem cell
• aging
• ASC
• CCCTC-binding factor
• CTCF
• differentially hydroxymethylated regions
• DHMR
• SAT
• subcutaneous adipose tissue
• ten–eleven translocation methylcytosine dioxygenase enzymes
• TET enzymes

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2019-0131

Financial & competing interests disclosure

This work was supported by the Polish National Science Centre grant 2014/13/B/NZ4/00157. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

This manuscript has been copyedited by native English speakers with a related biomedical background in BioMed Proofreading^® LLC. Writing assistance was supported by the Polish National Science Centre grant 2014/13/B/NZ4/00157.

Ethical conduct of research

The study was approved by the Bioethics Committee (KB/283/2013). All participants gave written, informed consent for participation in the study.

Additional information

Funding

This work was supported by the Polish National Science Centre grant 2014/13/B/NZ4/00157. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. The study was approved by the Bioethics Committee (KB/283/2013). All participants gave written, informed consent for participation in the study.