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DNA damage contributes to age-associated differences in SARS-CoV-2 infection.
Jin, Rui; Niu, Chang; Wu, Fengyun; Zhou, Sixin; Han, Tao; Zhang, Zhe; Li, Entao; Zhang, Xiaona; Xu, Shanrong; Wang, Jiadong; Tian, Shen; Chen, Wei; Ye, Qinong; Cao, Cheng; Cheng, Long.
  • Jin R; Beijing Institute of Biotechnology, Beijing, China.
  • Niu C; College of Life Sciences, Capital Normal University, Beijing, China.
  • Wu F; College of Life Sciences, Capital Normal University, Beijing, China.
  • Zhou S; Department of Surgery, Chinese PLA General Hospital, Beijing, China.
  • Han T; BaYi Children's Hospital, the Seventh Medical Center, Chinese PLA General Hospital, Beijing, China.
  • Zhang Z; Beijing Institute of Biotechnology, Beijing, China.
  • Li E; Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, China.
  • Zhang X; College of Life Sciences, Capital Normal University, Beijing, China.
  • Xu S; School of Life Science, Anqing Normal University, Anqing, China.
  • Wang J; Department of Radiation Medicine, School of Basic Medical Sciences, Institute of Systems Biomedicine, Peking University Health Science Center, Beijing, China.
  • Tian S; College of Life Sciences, Capital Normal University, Beijing, China.
  • Chen W; Beijing Institute of Biotechnology, Beijing, China.
  • Ye Q; Beijing Institute of Biotechnology, Beijing, China.
  • Cao C; Beijing Institute of Biotechnology, Beijing, China.
  • Cheng L; Beijing Institute of Biotechnology, Beijing, China.
Aging Cell ; : e13729, 2022 Oct 18.
Article in English | MEDLINE | ID: covidwho-2264783
ABSTRACT
Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is known to disproportionately affect older individuals. How aging processes affect SARS-CoV-2 infection and disease progression remains largely unknown. Here, we found that DNA damage, one of the hallmarks of aging, promoted SARS-CoV-2 infection in vitro and in vivo. SARS-CoV-2 entry was facilitated by DNA damage caused by extrinsic genotoxic stress or telomere dysfunction and hampered by inhibition of the DNA damage response (DDR). Mechanistic analysis revealed that DDR increased expression of angiotensin-converting enzyme 2 (ACE2), the primary receptor of SARS-CoV-2, by activation of transcription factor c-Jun. Importantly, in vivo experiment using a mouse-adapted viral strain also verified the significant roles of DNA damage in viral entry and severity of infection. Expression of ACE2 was elevated in the older human and mice tissues and positively correlated with γH2AX, a DNA damage biomarker, and phosphorylated c-Jun (p-c-Jun). Finally, nicotinamide mononucleotide (NMN) and MDL-800, which promote DNA repair, alleviated SARS-CoV-2 infection and disease severity in vitro and in vivo. Taken together, our data provide insights into the age-associated differences in SARS-CoV-2 infection and a novel approach for antiviral intervention.
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Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study Language: English Journal: Aging Cell Year: 2022 Document Type: Article Affiliation country: Acel.13729

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study Language: English Journal: Aging Cell Year: 2022 Document Type: Article Affiliation country: Acel.13729