1. Analysis of the machinery and intermediates of the 5hmC-mediated DNA demethylation pathway in aging on samples from the MARKAGE Study
- Author
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Valentini, Elisabetta, Zampieri, Michele, Malavolta, Marco, Bacalini, Maria Giulia, Calabrese, Roberta, Guastafierro, Tiziana, Reale, Anna, Franceschi, Claudio, Hervonen, Antti, Koller, Bernhard, Bernhardt, Jürgen, Slagboom, P. Eline, Toussaint, Olivier, Sikora, Ewa, Gonos, Efstathios S, Breusing, Nicolle, Grune, Tilman, Jansen, Eugène, Dollé, Martijn E.T., Moreno-Villanueva, María, Sindlinger, Thilo, Bürkle, Alexander, Ciccarone, Fabio, Caiafa, Paola, Valentini, Elisabetta, Zampieri, Michele, Malavolta, Marco, Bacalini, Maria Giulia, Calabrese, Roberta, Guastafierro, Tiziana, Reale, Anna, Franceschi, Claudio, Hervonen, Antti, Koller, Bernhard, Bernhardt, Jürgen, Eline Slagboom, P., Toussaint, Olivier, Sikora, Ewa, Gonos, Efstathios S., Breusing, Nicolle, Grune, Tilman, Jansen, Eugène, Dollé, Martijn E.T., Moreno-Villanueva, María, Sindlinger, Thilo, Bürkle, Alexander, Ciccarone, Fabio, and Caiafa, Paola
- Subjects
0301 basic medicine ,DNA Hydroxymethylation ,Adult ,Male ,Aging ,Gene Expression ,TDG ,Biology ,Dioxygenases ,Mixed Function Oxygenases ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,DNA hydroxymethylation ,TET genes ,Cell Biology ,ddc:570 ,Proto-Oncogene Proteins ,Humans ,Epigenetics ,Settore BIO/10 ,Aged ,Genetics ,Regulation of gene expression ,DNA Repair Pathway ,DNA Methylation ,Middle Aged ,5-Methylcytosine ,030104 developmental biology ,DNA demethylation ,chemistry ,Gene Expression Regulation ,genesTET ,aging ,030220 oncology & carcinogenesis ,DNA methylation ,Leukocytes, Mononuclear ,TET gene ,Female ,Thymine-DNA glycosylase ,Research Paper - 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. published
- Published
- 2016