New Publication: Senolytics reduce coronavirus-related mortality in old mice
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.
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, Meves A, Li M, Prakash YS, Chiarella SE, Hamilton SE, Tchkonia T, Niedernhofer LJ, Kirkland JL, Robbins PD. Senolytics reduce coronavirus-related mortality in old mice. Science. 2021 Jul 16;373(6552):eabe4832. doi: 10.1126/science.abe4832. Epub 2021 Jun 8. PMID: 34103349.