The role of extracellular DNA in COVID-19: Clues from inflamm-aging

Gianluca Storci, Francesca Bonifazi, Paolo Garagnani, Fabiola Olivieri, Massimiliano Bonafè

Research output: Contribution to journalReview articlepeer-review


Epidemiological data convey severe prognosis and high mortality rate for COVID-19 in elderly men affected by age-related diseases. These subjects develop local and systemic hyper-inflammation, which are associated with thrombotic complications and multi-organ failure. Therefore, understanding SARS-CoV-2 induced hyper-inflammation in elderly men is a pressing need. Here we focus on the role of extracellular DNA, mainly mitochondrial DNA (mtDNA) and telomeric DNA (telDNA) in the modulation of systemic inflammation in these subjects. In particular, extracellular mtDNA is regarded as a powerful trigger of the inflammatory response. On the contrary, extracellular telDNA pool is estimated to be capable of inhibiting a variety of inflammatory pathways. In turn, we underpin that telDNA reservoir is progressively depleted during aging, and that it is scarcer in men than in women. We propose that an increase in extracellular mtDNA, concomitant with the reduction of the anti-inflammatory telDNA reservoir may explain hyper-inflammation in elderly male affected by COVID-19. This scenario is reminiscent of inflamm-aging, the portmanteau word that depicts how aging and aging related diseases are intimately linked to inflammation.

Original languageEnglish
Article number101234
JournalAgeing Research Reviews
Publication statusPublished - Mar 2021


  • COVID-19
  • DNA sensing receptors
  • Inflamm-aging
  • Misplaced DNA
  • Telomere

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Ageing
  • Molecular Biology
  • Neurology


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