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Ketogenic diet restrains aging-induced exacerbation of coronavirus infection in mice.

Seungjin RyuIrina ShchukinaYun-Hee YoumHua QingBrandon HilliardTamara DlugosXinbo ZhangYuki YasumotoCarmen J BoothCarlos Fernández-HernandoYajaira SuárezKamal KhannaTamas L HorvathMarcelo O DietrichMaxim ArtyomovAndrew WangVishwa Deep Dixit
Published in: eLife (2021)
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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