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Aging and disease    2020, Vol. 11 Issue (4) : 756-762     DOI: 10.14336/AD.2020.0601
Opinion |
Age-induced NLRP3 Inflammasome Over-activation Increases Lethality of SARS-CoV-2 Pneumonia in Elderly Patients
Lara Pedro C1,2,3,*, Macías-Verde David1,2,3, Burgos-Burgos Javier1,2,3
1Hospital Universitario San Roque, Las Palmas, Spain
2Universidad Fernando Pessoa Canarias, Las Palmas, Spain
3Instituto Canario de Investigación del Cáncer, Tenerife, Spain
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Abstract  

Age is one of the most important prognostic factors associated to lethality in SARS-CoV-2 infection. In multivariate analysis, advanced age was an independent risk factor for death. Recent studies suggest a role for the nucleotide-binding domain and leucine rich repeat containing family, pyrin domain containing 3 (NLRP3) inflammasome activation in lung inflammation and fibrosis in SARS-CoV and SARS-CoV-2 infections. Increased NLRP3/ apoptosis-associated speck-like protein (ASC) mRNA expression and increased caspase-1 activity, have been observed in aged lung, provoking increased and heightened expression levels of mature Interleukin (IL)-1β and IL-18 in aged individuals. Aged individuals have a basal predisposition to over-react to infection, displaying an increased hyper-inflammatory cascade, that seems not to be fully physiologically controlled. NLRP3 inflammasome is over-activated in aged individuals, through deficient mitochondrial functioning, increased mitochondrial Reactive Oxigen Species (mtROS) and/or mitochondrial (mt)DNA, leading to a hyper-response of classically activated macrophages and subsequent increases in IL-1 β. This NLRP3 over-activated status in elderly individuals, is also observed in telomere dysfunctional mice models. In our opinion, the NLRP3 inflammasome plays a central role in the increased lethality observed in elderly patients infected by COVID-19. Strategies blocking inflammasome would deserve to be studied.

Keywords NLRP3      inflammasome      age      COVID-19      pneumonia     
Corresponding Authors: Lara Pedro C   
About author:

These authors contributed equally to this work.

Just Accepted Date: 14 June 2020   Issue Date: 30 July 2020
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Lara Pedro C
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Lara Pedro C,Macías-Verde David,Burgos-Burgos Javier. Age-induced NLRP3 Inflammasome Over-activation Increases Lethality of SARS-CoV-2 Pneumonia in Elderly Patients[J]. Aging and disease, 2020, 11(4): 756-762.
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