Ribosomal DNA instability: An evolutionary conserved fuel for inflammaging

Gianluca Storci, Maria Giulia Bacalini, Francesca Bonifazi, Paolo Garagnani, Sabrina De Carolis, Stefano Salvioli, Fabiola Olivieri, Massimiliano Bonafè

Research output: Contribution to journalReview articlepeer-review

Abstract

Across eukaryotes, ribosomal DNA (rDNA) loci are characterized by intrinsic genomic instability due to their repetitive nature and their base composition that facilitate DNA double strand breaks and RNA:DNA hybrids formation. In the yeast, ribosomal DNA instability affects lifespan via the formation of extrachromosomal rDNA circles (ERC) that accrue into aged cells. In humans, rDNA instability has long been reported in a variety of progeric syndromes caused by the dysfunction of DNA helicases, but its role in physiological aging and longevity still needs to be clarified. Here we propose that rDNA instability leads to the activation of innate immunity and inflammation via the interaction with the cytoplasmic DNA sensing machinery. Owing to the recent clarified role of cytoplasmic DNA in the pro-inflammatory phenotype of senescent cells, we hypothesize that the accrual of rDNA derived molecules (i.e. ERC and RNA:DNA hybrids) may have a role in aging by contributing to inflammaging i.e. the systemic pro-inflammatory drift that associates with the onset of geriatric syndromes and age related dysfunctions in humans.

Original languageEnglish
Article number101018
JournalAgeing Research Reviews
Volume58
DOIs
Publication statusPublished - Mar 2020

Keywords

  • DNA hybrid
  • Extrachromosomal rDNA circle (ERC)
  • Inflammaging
  • Ribosomal DNA (rDNA)
  • RNA

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Ageing
  • Molecular Biology
  • Neurology

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