{"id":"doi:10.1126/science.abe4832","kind":"article","title":"Senolytics reduce coronavirus-related mortality in old mice","authors":["Camell CD","Yousefzadeh MJ","Zhu Y","Prata LGPL","Huggins MA","Pierson M","Zhang L","O'Kelly RD","Pirtskhalava T","Xun P","Ejima K","Xue A","Tripathi U","Espindola-Netto JM","Giorgadze N","Atkinson EJ","Inman CL","Johnson KO","Cholensky SH","Carlson TW","LeBrasseur NK","Khosla S","O'Sullivan MG","Allison DB","Jameson SC"],"author_count":34,"year":2021,"published":"2021-06-08","venue":"Science (New York, N.Y.)","cited_by":276,"doi":"10.1126/science.abe4832","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1126/science.abe4832","archive_url":"https://space-kitty.com/papers/doi:10.1126/science.abe4832","updated":null,"pmid":"34103349","pmcid":"PMC8607935","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC8607935/pdf","abstract":"The COVID-19 pandemic has revealed the pronounced vulnerability of the elderly and chronically ill to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced morbidity and mortality. Cellular senescence contributes to inflammation, multiple chronic diseases, and age-related dysfunction, but effects on responses to viral infection are unclear. Here, we demonstrate that senescent cells (SnCs) become hyper-inflammatory in response to pathogen-associated molecular patterns (PAMPs), including SARS-CoV-2 spike protein-1, increasing expression of viral entry proteins and reducing antiviral gene expression in non-SnCs through a paracrine mechanism. Old mice acutely infected with pathogens that included a SARS-CoV-2-related mouse β-coronavirus experienced increased senescence and inflammation, with nearly 100% mortality. Targeting SnCs by using senolytic drugs before or after pathogen exposure significantly reduced mortality, cellular senescence, and inflammatory markers and increased antiviral antibodies. Thus, reducing the SnC burden in diseased or aged individuals should enhance resilience and reduce mortality after viral infection, including that of SARS-CoV-2.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Senolytics reduce coronavirus-related mortality in old mice\" by Camell CD, Yousefzadeh MJ, Zhu Y et al., https://doi.org/10.1126/science.abe4832, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"aging-longevity","name":"Biology of Aging & Longevity","domain_slug":"medicine"}],"cited_in_dossiers":[]}