Analysis of the machinery and intermediates of the 5hmC-mediated DNA demethylation pathway in aging on samples from the MARK-AGE Study
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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.
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VALENTINI, Elisabetta, Michele ZAMPIERI, Marco MALAVOLTA, Maria Giulia BACALINI, Roberta CALABRESE, Tiziana GUASTAFIERRO, Maria MORENO-VILLANUEVA, Thilo SINDLINGER, Alexander BÜRKLE, Paola CAIAFA, 2016. Analysis of the machinery and intermediates of the 5hmC-mediated DNA demethylation pathway in aging on samples from the MARK-AGE Study. In: Aging. 2016, 8(9), pp. 1896-1922. eISSN 1945-4589. Available under: doi: 10.18632/aging.101022BibTex
@article{Valentini2016Analy-37537, year={2016}, doi={10.18632/aging.101022}, title={Analysis of the machinery and intermediates of the 5hmC-mediated DNA demethylation pathway in aging on samples from the MARK-AGE Study}, number={9}, volume={8}, journal={Aging}, pages={1896--1922}, author={Valentini, Elisabetta and Zampieri, Michele and Malavolta, Marco and Bacalini, Maria Giulia and Calabrese, Roberta and Guastafierro, Tiziana and Moreno-Villanueva, Maria and Sindlinger, Thilo and Bürkle, Alexander and Caiafa, Paola} }
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