PXD041777-2

PXD041777 is an original dataset announced via ProteomeXchange.

Title	Removal of senescent cells reduces the viral load and attenuates pulmonary and systemic inflammation in SARS-CoV-2-infected, aged hamsters
Description	Older age is one of the strongest risk factors for COVID-19 morbidity and mortality. Here, we sought to determine whether age-associated cellular senescence contributes to the severity of COVID-19 by studying the well-established golden hamster model of SARS-CoV-2-driven lung disease. We found that aged hamsters (22 months of age) accumulate senescent cells in the lungs and that the senolytic drug ABT-263, a B cell lymphoma-2 family inhibitor, depletes these cells at baseline and during a SARS-CoV-2 infection. Relative to young hamsters (2 months of age), aged hamsters had a greater viral load during the acute phase of infection and displayed higher levels of sequelae during the post-acute phase. Interestingly, early treatment with ABT-263 was associated with a significantly lower pulmonary viral load, an effect associated with lower expression of angiotensin converting enzyme 2, the receptor for SARS-CoV-2, and an amelioration of COVID-19-like lung disease in aged (but not young) animals. ABT-263 treatment of aged animals was also associated with lower pulmonary and systemic levels of senescence-associated secretory phenotype factors. Furthermore, early removal of senescent cells reduced the longer-term pulmonary inflammation. These data demonstrate the causative role of age-associated pre-existing senescent cells on the pathologic severity of experimental COVID-19. As several senolytics have recently moved into early-stage clinical trials, our present findings have clear clinical relevance.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_07:00:27.951.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD041777
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	SALIOU Jean-Michel
SpeciesList	scientific name: Severe acute respiratory syndrome coronavirus 2; NCBI TaxID: NCBITaxon:2697049; scientific name: Mesocricetus auratus (Golden hamster); NCBI TaxID: 10036;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2023-04-24 07:56:34	ID requested
1	2023-07-03 08:05:11	announced
⏵ 2	2023-11-14 07:00:28	announced	2023-11-14: Updated project metadata.

10.6019/PXD041777;

submitter keyword: Senolytics,SARS-CoV-2, Aging, Systemic inflammation, Proteomics

Jean-michel Saliou
contact affiliation	Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, US 41 - UAR 2014 – PLBS, F-59000 Lille, France
contact email	jean-michel.saliou@pasteur-lille.fr
lab head
SALIOU Jean-Michel
contact affiliation	Institut Pasteur de Lille
contact email	jean-michel.saliou@pasteur-lille.fr
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD041777
     1. Label: PRIDE project
     2. Name: Removal of senescent cells reduces the viral load and attenuates pulmonary and systemic inflammation in SARS-CoV-2-infected, aged hamsters