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Open AccessArticle

Aging and Caloric Restriction Modulate the DNA Methylation Profile of the Ribosomal RNA Locus in Human and Rat Liver

Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum, 40138 Bologna, Italy
IRCCS Istituto delle Scienze Neurologiche di Bologna, 40 139 Bologna, Italy
Department of Laboratory Medicine, Division of Pathology, Karolinska Institutet, 171 76 Stockholm, Sweden
Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, 141-86, Stockholm, Sweden
Department of Laboratory Medicine, Karolinska Institute and Karolinska Universitetssjukhuset, 171 76 Stockholm, Sweden
Department of Biomedical Sciences, University of Cagliari, 09 124 Cagliari, Italy
Laboratory of Systems Medicine of Healthy Aging and Department of Applied Mathematics, Lobachevsky Univeristy, 603950 Nizhny Novgorod, Russia
Department of Laboratory Medicine, Clinical Chemistry, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, Sweden
Applied Biomedical Research Center (CRBA), Policlinico S. Orsola-Malpighi Polyclinic, 40 138 Bologna, Italy
CNR Institute of Molecular Genetics “Luigi Luca Cavalli-Sforza”, Unit of Bologna, 40136 Bologna, Italy
Author to whom correspondence should be addressed.
Co-first authorship.
Co-last authorship.
Nutrients 2020, 12(2), 277;
Received: 24 December 2019 / Revised: 13 January 2020 / Accepted: 17 January 2020 / Published: 21 January 2020
(This article belongs to the Special Issue Nutrition and Epigenetics)
A growing amount of evidence suggests that the downregulation of protein synthesis is an adaptive response during physiological aging, which positively contributes to longevity and can be modulated by nutritional interventions like caloric restriction (CR). The expression of ribosomal RNA (rRNA) is one of the main determinants of translational rate, and epigenetic modifications finely contribute to its regulation. Previous reports suggest that hypermethylation of ribosomal DNA (rDNA) locus occurs with aging, although with some species- and tissue- specificity. In the present study, we experimentally measured DNA methylation of three regions (the promoter, the 5′ of the 18S and the 5′ of 28S sequences) in the rDNA locus in liver tissues from rats at two, four, 10, and 18 months. We confirm previous findings, showing age-related hypermethylation, and describe, for the first time, that this gain in methylation also occurs in human hepatocytes. Furthermore, we show that age-related hypermethylation is enhanced in livers of rat upon CR at two and 10 months, and that at two months a trend towards the reduction of rRNA expression occurs. Collectively, our results suggest that CR modulates age-related regulation of methylation at the rDNA locus, thus providing an epigenetic readout of the pro-longevity effects of CR. View Full-Text
Keywords: aging; DNA methylation; liver; ribosomal RNA; caloric restriction aging; DNA methylation; liver; ribosomal RNA; caloric restriction
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Gensous, N.; Ravaioli, F.; Pirazzini, C.; Gramignoli, R.; Ellis, E.; Storci, G.; Capri, M.; Strom, S.; Laconi, E.; Franceschi, C.; Garagnani, P.; Marongiu, F.; Bacalini, M.G. Aging and Caloric Restriction Modulate the DNA Methylation Profile of the Ribosomal RNA Locus in Human and Rat Liver. Nutrients 2020, 12, 277.

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