Pathogenic Mechanism of SARS-CoV-2 Omicron Variant: Cellular Senescence Induction | Aging-US

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December 15, 2023

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  • Aging-US published this research paper as the #cover for Volume 15, Issue 23, entitled, "Uncovering a unique pathogenic mechanism of SARS-CoV-2 omicron variant: selective induction of cellular senescence" by researchers from the Institute of Medical Microbiology, Jena University Hospital, Jena 07747, Germany; Member of the Leibniz Centre for Photonics in Infection Research (LPI), Jena 07747, Germany; Medicine/Pulmonary and Critical Care Division, University of California San Francisco, San Francisco, CA; Else Kröner Graduate School for Medical Students “JSAM” Jena University Hospital, Jena 07747, Germany; Klinik für Herz- und Thoraxchirurgie, Jena 07747, Germany; Institute of Forensic Medicine, Jena University Hospital, Jena 07747, Germany; Institute of Forensic Medicine, University Hospital Bonn, University of Bonn, Bonn 53111, Germany. DOI - https://doi.org/10.18632/aging.205297 Corresponding author - Stefanie Deinhardt-Emmer - stefanie.deinhardt-emmer@med.uni-jena.de Abstract Background: SARS-CoV-2 variants are constantly emerging with a variety of changes in the conformation of the spike protein, resulting in alterations of virus entry mechanisms. Solely omicron variants use the endosomal clathrin-mediated entry. Here, we investigate the influence of defined altered spike formations to study their impact on premature cellular senescence. Methods: In our study, in vitro infections of SARS-CoV-2 variants delta (B.1.617.2) and omicron (B.1.1.529) were analyzed by using human primary small alveolar epithelial cells and human ex vivo lung slices. We confirmed cellular senescence in human lungs of COVID-19 patients. Hence, global gene expression patterns of infected human primary alveolar epithelial cells were identified via mRNA sequencing. Results: Solely omicron variants of SARS-CoV-2 influenced the expression of cell cycle genes, highlighted by an increased p21 expression in human primary lung cells and human ex vivo lungs. Additionally, an upregulated senescence-associated secretory phenotype (SASP) was detected. Transcriptomic data indicate an increased gene expression of p16, and p38 in omicron-infected lung cells. Conclusions: Significant changes due to different SARS-CoV-2 infections in human primary alveolar epithelial cells with an overall impact on premature aging could be identified. A substantially different cellular response with an upregulation of cell cycle, inflammation- and integrin-associated pathways in omicron infected cells indicates premature cellular senescence. Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.205297 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, SARS-CoV-2, variant of concern, cellular senescence, lung airway cells About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at https://www.Aging-US.com​​ and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

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