Ribosomal DNA instability: An evolutionary conserved fuel for inflammaging.
DNA hybrid
Extrachromosomal rDNA circle (ERC)
Inflammaging
RNA
Ribosomal DNA (rDNA)
Journal
Ageing research reviews
ISSN: 1872-9649
Titre abrégé: Ageing Res Rev
Pays: England
ID NLM: 101128963
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
received:
12
07
2019
revised:
07
12
2019
accepted:
08
01
2020
pubmed:
14
1
2020
medline:
4
11
2020
entrez:
14
1
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31926964
pii: S1568-1637(19)30219-3
doi: 10.1016/j.arr.2020.101018
pii:
doi:
Substances chimiques
DNA, Ribosomal
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
101018Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.