%0 Journal Article %A %A Valentini E.%A %A Zampieri M.%A %A Malavolta M.%A %A Bacalini M.G.%A %A Calabrese R.%A %A Guastafierro T.%A %A Reale A.%A %A Franceschi C.%A %A Hervonen A.%A %A Koller B.%A et al. %D 2016 %T Analysis of the machinery and intermediates of the 5hmC-mediated DNA demethylation pathway in aging on samples from the MARKAGE Study %J Aging %V 8 %@ 1945-4589 %R 10.18632/aging.101022 %I Impact Journals LLC %P 1896–1922 %N 9 %U https://hdl.handle.net/10442/17500 %X Gradual changes in the DNA methylation landscape occur throughout aging virtually in all human tissues. A widespread reduction of 5-methylcytosine (5mC), associated with highly reproducible site-specific hypermethylation, characterizes the genome in aging. Therefore, an equilibrium seems to exist between general and directional deregulating events concerning DNA methylation controllers, which may underpin the age-related epigenetic changes. In this context, 5mC-hydroxylases (TET enzymes) are new potential players. In fact, TETs catalyze the stepwise oxidation of 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC), driving the DNA demethylation process based on thymine DNA glycosylase (TDG)-mediated DNA repair pathway. The present paper reports the expression of DNA hydroxymethylation components, the levels of 5hmC and of its derivatives in peripheral blood mononuclear cells of age-stratified donors recruited in several European countries in the context of the EU Project “MARK-AGE”. The results provide evidence for an age-related decline of TET1, TET3 and TDG gene expression along with a decrease of 5hmC and an accumulation of 5caC. These associations were independent of confounding variables, including recruitment center, gender and leukocyte composition. The observed impairment of 5hmC-mediated DNA demethylation pathway in blood cells may lead to aberrant transcriptional programs in the elderly. %> Αποθετήριο Ήλιος / ΕΙΕ