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Senolytics reduce coronavirus-related mortality in old mice
Christina D Camell # 1, Matthew J Yousefzadeh # 1, Yi Zhu # 2 3, Larissa G P Langhi Prata # 2, Matthew A Huggins 4, Mark Pierson 4, Lei Zhang 1, Ryan D O'Kelly 1, Tamar Pirtskhalava 2, Pengcheng Xun 5, Keisuke Ejima 5, Ailing Xue 2, Utkarsh Tripathi 2, Jair Machado Espindola-Netto 2, Nino Giorgadze 2, Elizabeth J Atkinson 2 6, Christina L Inman 2, Kurt O Johnson 2, Stephanie H Cholensky 1, Timothy W Carlson 7 8, Nathan K LeBrasseur 2 9, Sundeep Khosla 2 10, M Gerard O'Sullivan 7 8, David B Allison 5, Stephen C Jameson 4, Alexander Meves 11, Ming Li 11, Y S Prakash 3 12, Sergio E Chiarella 13, Sara E Hamilton 14, Tamara Tchkonia 15 3, Laura J Niedernhofer 16, James L Kirkland 15 3 17, Paul D Robbins 16
Abstract:
...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.
PMID: 34103349
Free Full-Text: https://science.sciencemag.org/content/373/6552/eabe4832
SENS Approach:
