Preprint Hypothesis Version 1 Preserved in Portico This version is not peer-reviewed

Inflamm-Aging: Why Older Men Are the Most Susceptible to SARS-Cov-2 Complicated Outcomes

Version 1 : Received: 7 April 2020 / Approved: 9 April 2020 / Online: 9 April 2020 (08:38:22 CEST)



A peer-reviewed article of this Preprint also exists. Bonafè, M.; Prattichizzo, F.; Giuliani, A.; Storci, G.; Sabbatinelli, J.; Olivieri, F. Inflamm-aging: why older men are the most susceptible to SARS-CoV-2 complicated outcomes. Cytokine & Growth Factor Reviews 2020, doi:10.1016/j.cytogfr.2020.04.005. Bonafè, M.; Prattichizzo, F.; Giuliani, A.; Storci, G.; Sabbatinelli, J.; Olivieri, F. Inflamm-aging: why older men are the most susceptible to SARS-CoV-2 complicated outcomes. Cytokine & Growth Factor Reviews 2020, doi:10.1016/j.cytogfr.2020.04.005. Copy Journal reference: Cytokine & Growth Factor Reviews 2020

DOI: 10.1016/j.cytogfr.2020.04.005

Cite as: Bonafè, M.; Prattichizzo, F.; Giuliani, A.; Storci, G.; Sabbatinelli, J.; Olivieri, F. Inflamm-aging: why older men are the most susceptible to SARS-CoV-2 complicated outcomes. Cytokine & Growth Factor Reviews 2020, doi:10.1016/j.cytogfr.2020.04.005. Bonafè, M.; Prattichizzo, F.; Giuliani, A.; Storci, G.; Sabbatinelli, J.; Olivieri, F. Inflamm-aging: why older men are the most susceptible to SARS-CoV-2 complicated outcomes. Cytokine & Growth Factor Reviews 2020, doi:10.1016/j.cytogfr.2020.04.005. Copy CANCEL COPY CITATION DETAILS

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is characterized by a high mortality of elderly men with age-related comorbidities. In most of these patients, uncontrolled local and systemic hyperinflammation induces severe and often lethal outcomes. The aging process is characterized by the gradual development of a chronic subclinical systemic inflammation (inflamm-aging) and by acquired immune system impairment (immune senescence). Here, we advance the hypothesis that some key features of aging contribute to the disproportionate SARS-CoV-2 mortality suffered by elderly men. At least four well-recognized aging-related characteristics that are strongly expressed in older men go some way towards explaining why these patients account for the vast majority of fatalities: i. the presence of subclinical systemic inflammation without overt disease, ii. a blunted acquired immune system and type I interferon response due to the chronic inflammation; iii. the downregulation of ACE2 (SARS-CoV-2 receptor), which triggers inflammation, particularly in patients with age-related comorbid diseases such as type II diabetes; and iv. accelerated biological aging, as measured by epigenetic and senescence markers (e.g. telomere shortening) associated to the chronic inflammatory state. Though typical of the aged, especially of elderly men, it is conceivable that these features are also shared by some subsets of the younger population. The high mortality rate of SARS-CoV-2 infection suggests that clarification of the mechanisms of inflamm-aging and immune senescence can help combat not only age-related disorders but also SARS-CoV-2 infection.

Subject Areas

SARS-CoV-2; COVID-19; IL-6; inflamm-aging; immune senescence; host-directed therapies

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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