Inflamm-aging: Why older men are the most susceptible to SARS-CoV-2 complicated outcomes

Massimiliano Bonafè, Francesco Prattichizzo, Angelica Giuliani, Gianluca Storci, Jacopo Sabbatinelli, Fabiola Olivieri

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)33-37
Number of pages5
JournalCytokine and Growth Factor Reviews
Publication statusPublished - Jun 2020


  • Cardiovascular diseases
  • COVID-19
  • Host-directed therapies
  • Inflamm-aging
  • interleukin-6
  • SARS-CoV-2

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Immunology and Allergy
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)


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