Senolytics reduce coronavirus-related mortality in old mice.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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История · было → стало
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Camell Christina D, Yousefzadeh Matthew J, Zhu Yi, Prata Larissa G P Langhi, Huggins Matthew A, Pierson Mark, Zhang Lei, O'Kelly Ryan D, Pirtskhalava Tamar, Xun Pengcheng, Ejima Keisuke, Xue Ailing, Tripathi Utkarsh, Espindola-Netto Jair Machado, Giorgadze Nino, Atkinson Elizabeth J, Inman Christina L, Johnson Kurt O, Cholensky Stephanie H, Carlson Timothy W, LeBrasseur Nathan K, Khosla Sundeep, O'Sullivan M Gerard, Allison David B, Jameson Stephen C, Meves Alexander, Li Ming, Prakash Y S, Chiarella Sergio E, Hamilton Sara E, Tchkonia Tamara, Niedernhofer Laura J, Kirkland James L, Robbins Paul D
Аннотация
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.