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Senolytics reduce coronavirus-related mortality in old mice.
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.
  • Camell CD; Institute on the Biology of Aging and Metabolism, Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA.
  • Yousefzadeh MJ; Institute on the Biology of Aging and Metabolism, Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA.
  • Zhu Y; Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA.
  • Prata LGPL; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA.
  • Huggins MA; Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA.
  • Pierson M; Department of Laboratory Medicine and Pathology and Center of Immunology, University of Minnesota, Minneapolis, MN, USA.
  • Zhang L; Department of Laboratory Medicine and Pathology and Center of Immunology, University of Minnesota, Minneapolis, MN, USA.
  • O'Kelly RD; Institute on the Biology of Aging and Metabolism, Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA.
  • Pirtskhalava T; Institute on the Biology of Aging and Metabolism, Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA.
  • Xun P; Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA.
  • Ejima K; Department of Epidemiology and Biostatistics, School of Public Health, Indiana University-Bloomington, Bloomington, IN, USA.
  • Xue A; Department of Epidemiology and Biostatistics, School of Public Health, Indiana University-Bloomington, Bloomington, IN, USA.
  • Tripathi U; Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA.
  • Espindola-Netto JM; Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA.
  • Giorgadze N; Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA.
  • Atkinson EJ; Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA.
  • Inman CL; Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA.
  • Johnson KO; Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
  • Cholensky SH; Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA.
  • Carlson TW; Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA.
  • LeBrasseur NK; Institute on the Biology of Aging and Metabolism, Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA.
  • Khosla S; Masonic Cancer Center Comparative Pathology Shared Resource, University of Minnesota, St. Paul, MN, USA.
  • O'Sullivan MG; Department of Veterinary Population Medicine, University of Minnesota, St. Paul, MN, USA.
  • Allison DB; Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA.
  • Jameson SC; Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN, USA.
  • Meves A; Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA.
  • Li M; Division of Endocrinology, Department of Medicine, Mayo Clinic, Rochester, MN, USA.
  • Prakash YS; Masonic Cancer Center Comparative Pathology Shared Resource, University of Minnesota, St. Paul, MN, USA.
  • Chiarella SE; Department of Veterinary Population Medicine, University of Minnesota, St. Paul, MN, USA.
  • Hamilton SE; Department of Epidemiology and Biostatistics, School of Public Health, Indiana University-Bloomington, Bloomington, IN, USA.
  • Tchkonia T; Department of Laboratory Medicine and Pathology and Center of Immunology, University of Minnesota, Minneapolis, MN, USA.
  • Niedernhofer LJ; Department of Dermatology, Mayo Clinic, Rochester, MN, USA.
  • Kirkland JL; Department of Dermatology, Mayo Clinic, Rochester, MN, USA.
  • Robbins PD; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA.
Science ; 373(6552)2021 07 16.
Article in English | MEDLINE | ID: covidwho-1262378
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 ß-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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Aging / Cellular Senescence / Coronavirus Infections / Flavonols / Spike Glycoprotein, Coronavirus / Pathogen-Associated Molecular Pattern Molecules Type of study: Experimental Studies / Prognostic study Limits: Animals / Female / Humans / Male Language: English Year: 2021 Document Type: Article Affiliation country: Science.abe4832

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Aging / Cellular Senescence / Coronavirus Infections / Flavonols / Spike Glycoprotein, Coronavirus / Pathogen-Associated Molecular Pattern Molecules Type of study: Experimental Studies / Prognostic study Limits: Animals / Female / Humans / Male Language: English Year: 2021 Document Type: Article Affiliation country: Science.abe4832