Back to Search
Start Over
Ribosomal DNA instability: An evolutionary conserved fuel for inflammaging
- Publication Year :
- 2020
-
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.
- Subjects :
- 0301 basic medicine
Genome instability
DNA Replication
Aging
Saccharomyces cerevisiae
Biochemistry
DNA, Ribosomal
Genomic Instability
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
DNA hybrid
Extrachromosomal DNA
Humans
Molecular Biology
Ribosomal DNA
Aged
Genetics
Innate immune system
biology
Ribosomal DNA (rDNA)
RNA
Helicase
Phenotype
Inflammaging
Biological Evolution
030104 developmental biology
Neurology
chemistry
biology.protein
Extrachromosomal rDNA circle (ERC)
030217 neurology & neurosurgery
DNA
Biotechnology
Human
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....13dbd9dd64af7c7e3e28eba4b2e5f553