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

Seungjin Ryu, Irina Shchukina, Yun Hee Youm, Hua Qing, Brandon Hilliard, Tamara Dlugos, Xinbo Zhang, Yuki Yasumoto, Carmen J. Booth, Carlos Fernández-Hernando, Yajaira Suárez, Kamal Khanna, Tamas L. Horvath, Marcelo O. Dietrich, Maxim Artyomov, Andrew Wang, Vishwa Deep Dixit

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

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 gd T cells in lungs. Activation of ketogenesis in aged mice expands tissue protective gd 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.

Original languageEnglish
Article numbere66522
JournaleLife
Volume10
DOIs
StatePublished - Jun 2021

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