Joanna Borkowska1, Anna Domaszewska-Szostek1, Paulina Kołodziej2, Zofia Wicik1, Jacek Połosak1, Olga Buyanovskaya1, Lukasz Charzewski3, Marek Stańczyk4, Bartłomiej Noszczyk5, Monika Puzianowska-Kuznicka1,2. 1. Department of Human Epigenetics, Mossakowski Medical Research Centre, PAS, 5 Pawinskiego Street, 02-106 Warsaw, Poland. 2. Department of Geriatrics & Gerontology, Medical Centre of Postgraduate Education, 61/63 Kleczewska Street, 01-826 Warsaw, Poland. 3. Faculty of Physics, University of Warsaw, 5 Pasteur Street, 02-093 Warsaw, Poland. 4. Department of General Surgery, Wolski Hospital, 17 Kasprzaka Street, 01-211 Warsaw, Poland. 5. Department of Plastic Surgery, Medical Centre of Postgraduate Education, 99/103 Marymoncka Street, 01-813 Warsaw, Poland.
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.
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.