Cellular senescence as a potential mediator of COVID‐19 severity in the elderly

Abstract

SARS-CoV-2 is a novel betacoronavirus which infects the lower respiratory tract and can cause coronavirus disease 2019 (COVID-19), a complex respiratory distress syn-drome. Epidemiological data show that COVID-19 has a rising mortality particularly in individuals with advanced age. Identifying a functional association between SARS-CoV-2 infection and the process of biological aging may provide a tractable avenue for therapy to prevent acute and long-term disease. Here, we discuss how cellular senes-cence—a state of stable growth arrest characterized by pro-inflammatory and pro-dis-ease functions—can hypothetically be a contributor to COVID-19 pathogenesis, and a potential pharmaceutical target to alleviate disease severity. First, we define why older COVID-19 patients are more likely to accumulate high levels of cellular senescence. Second, we describe how senescent cells can contribute to an uncontrolled SARS-CoV-2-mediated cytokine storm and an excessive inflammatory reaction during the early phase of the disease. Third, we discuss the various mechanisms by which senes-cent cells promote tissue damage leading to lung failure and multi-tissue dysfunctions. Fourth, we argue that a high senescence burst might negatively impact on vaccine ef-ficacy. Measuring the burst of cellular senescence could hypothetically serve as a pre-dictor of COVID-19 severity, and targeting senescence-associated mechanisms prior and after SARS-CoV-2 infection might have the potential to limit a number of severe damages and to improve the efficacy of vaccinations.

Rights

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.© 2020 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd

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DOI

https://doi.org/10.1111/acel.13237

Repository URI

https://www.research.ed.ac.uk/en/publications/dddc9adf-7b7a-42ae-a7b5-41af846bd25d