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PXD041973-1

PXD041973 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleRemoval of senescent cells reduces the viral load and attenuates pulmonary and systemic inflammation in SARS-CoV-2-infected, aged hamsters
DescriptionOlder 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.
HostingRepositoryPRIDE
AnnounceDate2023-07-03
AnnouncementXMLSubmission_2023-07-03_08:02:34.634.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterSALIOUJean-Michel
SpeciesList scientific name: Mesocricetus auratus (Golden hamster); NCBI TaxID: 10036;
ModificationListTMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-05-04 02:03:23ID requested
12023-07-03 08:02:34announced
22023-11-14 07:00:27announced2023-11-14: Updated project metadata.
Publication List
Keyword List
submitter keyword: Senolytics,SARS-CoV-2, Aging, Systemic inflammation, Proteomics
Contact List
Jean-michelSaliou
contact affiliationUniv. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, US41 – UMS 2014 – PLBS, F-59000 Lille, France
contact emailjean-michel.saliou@pasteur-lille.fr
lab head
SALIOUJean-Michel
contact affiliationInstitut Pasteur de Lille
contact emailjean-michel.saliou@pasteur-lille.fr
dataset submitter
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