Inflamm-aging: Why older men are the most susceptible to SARS-CoV-2 complicated outcomes
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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 four well-recognized features of aging contribute to the disproportionate SARS-CoV-2 mortality suffered by elderly men: 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 (i.e. the SARS-CoV-2 receptor); and iv. accelerated biological aging. 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.
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The rate of "inflammaging" is also greater in men, driving a gap in male and female life expectancies.
“The rate of “inflammaging” is also greater in men [33–35], driving a gap in male and female life expectancies.”
From Age, sex and Alzheimer’s disease: a longitudinal study of 3xTg-AD mice reveals sex-specific disease trajectories and inflammatory responses mirrored in postmortem brains from Alzheimer’s patients (2024) · cites this paper as [35]
The section “In older men, accelerated inflamm-aging worsens COVID-19 infection outcomes” says men have a higher rate of inflamm-aging than women. The copy does not establish that this difference drives the gap in male and female life expectancies; its discussion of mortality concerns COVID-19 outcomes. (LLM, conf=0.86)
Experimental — accuracy not yet measuredMales experience more unfavorable changes and a greater rate of inflammaging or innate immune response than females.
“While both sexes experience aging-associated changes in immune function [32, 33], males have been shown to experience more unfavorable changes and a greater rate of inflammaging [34, 35] or innate immune response.”
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Kandhaya‐Pillai, R., Yang, X., Tchkonia, T., Martin, G. M., Kirkland, J. L., & Oshima, J. (2022) · Aging Cell · doi:10.1111/acel.13646 · Cited by 119 · see citing works
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- Authors
- Bonafè, M., Prattichizzo, F., Giuliani, A., Storci, G., Sabbatinelli, J., & Olivieri, F.
- Affiliations
- University of Bologna (IT)
- MultiMedica (IT)
- Marche Polytechnic University (IT)
- Corresponding author
- Prattichizzo, Francesco
- Giuliani, Angelica
- ORCID
- Venue
- Cytokine & Growth Factor Reviews
- Publisher
- Elsevier BV
- Published
- 2020-06
- Volume
- 53
- Pages
- 33-37
- ISSN
- 1359-6101 (ISSN-L)
- PMC
- PMC7252014
- OpenAlex
- W3016200057
- Cited by
- 184
- References
- 14
- Citations by year
- 2026: 3 · 2025: 11 · 2024: 21 · 2023: 17 · 2022: 41 · 2021: 52 · 2020: 39
- FWCI
- 1.74
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Cytokine & Growth Factor Reviews (publishedVersion)
- Preprints.org (acceptedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
- Università Politecnica delle Marche (Università Politecnica delle Marche) (submittedVersion, cc-by-nc-nd)
- Funders
- Ministero della Salute
- Topics
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Keywords
- inflammaging, SARS-CoV-2, COVID-19 mortality, older men, immunosenescence, hyperinflammation, type I interferon response, ACE2 downregulation, biological aging, chronic systemic inflammation, sex differences in aging
- MeSH terms
- Betacoronavirus, Angiotensin-Converting Enzyme 2, COVID-19, SARS-CoV-2, Interleukin-6 Inhibitors, Aged, Aged, 80 and over, Aging, Female, Humans, Inflammation, Interferon Type I, Peptidyl-Dipeptidase A, Male, Pneumonia, Viral, Interleukin-6, Comorbidity, Coronavirus Infections, Severe Acute Respiratory Syndrome, Pandemics, Antibodies, Monoclonal, Humanized
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