Abstract:
: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.
journal_name
Aging (Albany NY)journal_title
Agingauthors
Valentini E,Zampieri M,Malavolta M,Bacalini MG,Calabrese R,Guastafierro T,Reale A,Franceschi C,Hervonen A,Koller B,Bernhardt J,Slagboom PE,Toussaint O,Sikora E,Gonos ES,Breusing N,Grune T,Jansen E,Dollé ME,Moreno-Vidoi
10.18632/aging.101022subject
Has Abstractpub_date
2016-08-29 00:00:00pages
1896-1922issue
9issn
1945-4589pii
101022journal_volume
8pub_type
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