Dataset Information

Senolytics reduce coronavirus-related mortality in old mice.

ABSTRACT: The COVID-19 pandemic has revealed the pronounced vulnerability of the elderly and chronically ill to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced morbidity and mortality. Cellular senescence contributes to inflammation, multiple chronic diseases, and age-related dysfunction, but effects on responses to viral infection are unclear. Here, we demonstrate that senescent cells (SnCs) become hyper-inflammatory in response to pathogen-associated molecular patterns (PAMPs), including SARS-CoV-2 spike protein-1, increasing expression of viral entry proteins and reducing antiviral gene expression in non-SnCs through a paracrine mechanism. Old mice acutely infected with pathogens that included a SARS-CoV-2-related mouse β-coronavirus experienced increased senescence and inflammation, with nearly 100% mortality. Targeting SnCs by using senolytic drugs before or after pathogen exposure significantly reduced mortality, cellular senescence, and inflammatory markers and increased antiviral antibodies. Thus, reducing the SnC burden in diseased or aged individuals should enhance resilience and reduce mortality after viral infection, including that of SARS-CoV-2.

SUBMITTER: Camell CD

PROVIDER: S-EPMC8607935 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Senolytics reduce coronavirus-related mortality in old mice.

Camell Christina D CD Yousefzadeh Matthew J MJ Zhu Yi Y Prata Larissa G P Langhi LGPL Huggins Matthew A MA Pierson Mark M Zhang Lei L O'Kelly Ryan D RD Pirtskhalava Tamar T Xun Pengcheng P Ejima Keisuke K Xue Ailing A Tripathi Utkarsh U Espindola-Netto Jair Machado JM Giorgadze Nino N Atkinson Elizabeth J EJ Inman Christina L CL Johnson Kurt O KO Cholensky Stephanie H SH Carlson Timothy W TW LeBrasseur Nathan K NK Khosla Sundeep S O'Sullivan M Gerard MG Allison David B DB Jameson Stephen C SC Meves Alexander A Li Ming M Prakash Y S YS Chiarella Sergio E SE Hamilton Sara E SE Tchkonia Tamara T Niedernhofer Laura J LJ Kirkland James L JL Robbins Paul D PD

Science (New York, N.Y.) 20210608 6552

The COVID-19 pandemic has revealed the pronounced vulnerability of the elderly and chronically ill to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced morbidity and mortality. Cellular senescence contributes to inflammation, multiple chronic diseases, and age-related dysfunction, but effects on responses to viral infection are unclear. Here, we demonstrate that senescent cells (SnCs) become hyper-inflammatory in response to pathogen-associated molecular patterns (PAMPs), incl ...[more]

PMID: 34103349

Similar Datasets

Project description:ObjectiveTo replicate and analyse the information available to UK policymakers when the lockdown decision was taken in March 2020 in the United Kingdom.DesignIndependent calculations using the CovidSim code, which implements Imperial College London's individual based model, with data available in March 2020 applied to the coronavirus disease 2019 (covid-19) epidemic.SettingSimulations considering the spread of covid-19 in Great Britain and Northern Ireland.PopulationAbout 70 million simulated people matched as closely as possible to actual UK demographics, geography, and social behaviours.Main outcome measuresReplication of summary data on the covid-19 epidemic reported to the UK government Scientific Advisory Group for Emergencies (SAGE), and a detailed study of unpublished results, especially the effect of school closures.ResultsThe CovidSim model would have produced a good forecast of the subsequent data if initialised with a reproduction number of about 3.5 for covid-19. The model predicted that school closures and isolation of younger people would increase the total number of deaths, albeit postponed to a second and subsequent waves. The findings of this study suggest that prompt interventions were shown to be highly effective at reducing peak demand for intensive care unit (ICU) beds but also prolong the epidemic, in some cases resulting in more deaths long term. This happens because covid-19 related mortality is highly skewed towards older age groups. In the absence of an effective vaccination programme, none of the proposed mitigation strategies in the UK would reduce the predicted total number of deaths below 200 000.ConclusionsIt was predicted in March 2020 that in response to covid-19 a broad lockdown, as opposed to a focus on shielding the most vulnerable members of society, would reduce immediate demand for ICU beds at the cost of more deaths long term. The optimal strategy for saving lives in a covid-19 epidemic is different from that anticipated for an influenza epidemic with a different mortality age profile.

Dataset Information

Senolytics reduce coronavirus-related mortality in old mice.

Publications

Senolytics reduce coronavirus-related mortality in old mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets