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Ketogenic diet restrains aging-induced exacerbation of coronavirus infection in mice.
Ryu, Seungjin; Shchukina, Irina; Youm, Yun-Hee; Qing, Hua; Hilliard, Brandon; Dlugos, Tamara; Zhang, Xinbo; Yasumoto, Yuki; Booth, Carmen J; Fernández-Hernando, Carlos; Suárez, Yajaira; Khanna, Kamal; Horvath, Tamas L; Dietrich, Marcelo O; Artyomov, Maxim; Wang, Andrew; Dixit, Vishwa Deep.
  • Ryu S; Department of Comparative Medicine, Yale School of Medicine, New Haven, United States.
  • Shchukina I; Department of Immunobiology, Yale School of Medicine, New Haven, United States.
  • Youm YH; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, United States.
  • Qing H; Department of Comparative Medicine, Yale School of Medicine, New Haven, United States.
  • Hilliard B; Department of Immunobiology, Yale School of Medicine, New Haven, United States.
  • Dlugos T; Department of Internal Medicine, Yale School of Medicine, New Haven, United States.
  • Zhang X; Department of Internal Medicine, Yale School of Medicine, New Haven, United States.
  • Yasumoto Y; Department of Comparative Medicine, Yale School of Medicine, New Haven, United States.
  • Booth CJ; Department of Immunobiology, Yale School of Medicine, New Haven, United States.
  • Fernández-Hernando C; Department of Comparative Medicine, Yale School of Medicine, New Haven, United States.
  • Suárez Y; Department of Comparative Medicine, Yale School of Medicine, New Haven, United States.
  • Khanna K; Department of Comparative Medicine, Yale School of Medicine, New Haven, United States.
  • Horvath TL; Department of Comparative Medicine, Yale School of Medicine, New Haven, United States.
  • Dietrich MO; Program in Integrative Cell Signaling and Neurobiology of Metabolism, Yale School of Medicine, New Haven, United States.
  • Artyomov M; Department of Comparative Medicine, Yale School of Medicine, New Haven, United States.
  • Wang A; Program in Integrative Cell Signaling and Neurobiology of Metabolism, Yale School of Medicine, New Haven, United States.
  • Dixit VD; Department of Microbiology, New York University Langone Health, New York, United States.
Elife ; 102021 06 21.
Artigo em Inglês | MEDLINE | ID: covidwho-1278699
ABSTRACT
Increasing age is the strongest predictor of risk of COVID-19 severity and mortality. Immunometabolic switch from glycolysis to ketolysis protects against inflammatory damage and influenza infection in adults. To investigate how age compromises defense against coronavirus infection, and whether a pro-longevity ketogenic diet (KD) impacts immune surveillance, we developed an aging model of natural murine beta coronavirus (mCoV) infection with mouse hepatitis virus strain-A59 (MHV-A59). When inoculated intranasally, mCoV is pneumotropic and recapitulates several clinical hallmarks of COVID-19 infection. Aged mCoV-A59-infected mice have increased mortality and higher systemic inflammation in the heart, adipose tissue, and hypothalamus, including neutrophilia and loss of γδ T cells in lungs. Activation of ketogenesis in aged mice expands tissue protective γδ T cells, deactivates the NLRP3 inflammasome, and decreases pathogenic monocytes in lungs of infected aged mice. These data establish harnessing of the ketogenic immunometabolic checkpoint as a potential treatment against coronavirus infection in the aged.
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Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Assunto principal: Infecções por Coronavirus / Vírus da Hepatite Murina / Dieta Cetogênica Tipo de estudo: Estudo prognóstico Limite: Animais / Humanos / Masculino Idioma: Inglês Ano de publicação: 2021 Tipo de documento: Artigo País de afiliação: ELife.66522

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Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Assunto principal: Infecções por Coronavirus / Vírus da Hepatite Murina / Dieta Cetogênica Tipo de estudo: Estudo prognóstico Limite: Animais / Humanos / Masculino Idioma: Inglês Ano de publicação: 2021 Tipo de documento: Artigo País de afiliação: ELife.66522