Aging and caloric restriction modulate the dna methylation profile of the ribosomal rna locus in human and rat liver

Noémie Gensous, Francesco Ravaioli, Chiara Pirazzini, Roberto Gramignoli, Ewa Ellis, Gianluca Storci, Miriam Capri, Stephen Strom, Ezio Laconi, Claudio Franceschi, Paolo Garagnani, Fabio Marongiu, Maria Giulia Bacalini

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number277
JournalNutrients
Volume12
Issue number2
DOIs
Publication statusPublished - Feb 2020

Keywords

  • Aging
  • Caloric restriction
  • DNA methylation
  • Liver
  • Ribosomal RNA

ASJC Scopus subject areas

  • Food Science
  • Nutrition and Dietetics

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