Role of Senescence and Aging in SARS-CoV-2 Infection and COVID-19 Disease

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Abstract

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in a global pandemic associated with substantial morbidity and mortality worldwide, with particular risk for severe disease and mortality in the elderly population. SARS-CoV-2 infection is driven by a pathological hyperinflammatory response which results in a dysregulated immune response. Current advancements in aging research indicates that aging pathways have fundamental roles in dictating healthspan in addition to lifespan. Our review discusses the aging immune system and highlights that senescence and aging together, play a central role in COVID-19 pathogenesis. In our review, we primarily focus on the immune system response to SARS-CoV-2 infection, the interconnection between severe COVID-19, immunosenescence, aging, vaccination, and the emerging problem of Long-COVID. We hope to highlight the importance of identifying specific senescent endotypes (or “sendotypes”), which can used as determinants of COVID-19 severity and mortality. Indeed, identified sendotypes could be therapeutically exploited for therapeutic intervention. We highlight that senolytics, which eliminate senescent cells, can target aging-associated pathways and therefore are proving attractive as potential therapeutic options to alleviate symptoms, prevent severe infection, and reduce mortality burden in COVID-19 and thus ultimately enhance healthspan.
Original languageEnglish
Article number3367
Number of pages29
JournalCells
Volume10
Issue number12
Early online date30 Nov 2021
DOIs
Publication statusPublished online - 30 Nov 2021

Bibliographical note

Funding Information:
This research was funded by the PHA/HSC R&D Division (COM/5618/20) and the Western Health & Social Care Trust grants to T.S.R. D.S.G. acknowledges funding from UK RI (NCSi4P), Versus Arthritis (22703) and PHA/HSC R&D Division (COM/5631/20). G.G. is recipient of Vice-Chancellor’s Research Studentship from Ulster University. The NI Centre for Stratified Medicine has been funded by a grant to A.J.B. under the EU Regional Development Fund EU Sustainable Competitiveness Programme for NI & the NI Public Health Agency.

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • senescence
  • aging
  • COVID-19
  • SARS-CoV-2
  • immunosenescence
  • sendotypes
  • severity
  • mortality
  • vaccination
  • senolytics

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