Logo do repositório
 
Publicação

Age-dependent disease tolerance to SARS-CoV-2 infection

2026-06-30Preprint Acesso aberto
Ver registo simples
dc.contributor.authorRastogi, Sónia Trikha
dc.contributor.authorMesquita, Miguel
dc.contributor.authorFonseca, Diogo Martins
dc.contributor.authorSalazar, Sara
dc.contributor.authorCardoso, Sílvia
dc.contributor.authorFaisca, Pedro
dc.contributor.authorDrotleff, Bernhard
dc.contributor.authorAlenquer, Marta
dc.contributor.authorLone, Jean-Christophe
dc.contributor.authorMiguel, Verónica
dc.contributor.authorSancho, David
dc.contributor.authorHerrero, Laura
dc.contributor.authorPaixão, Tiago
dc.contributor.authorAmorim, Maria João
dc.contributor.authorJentho, Elisa
dc.contributor.authorGraça, Luís
dc.contributor.authorKitoko, Jamil Zola
dc.contributor.authorSoares, Miguel P.
dc.date.accessioned2026-07-30T15:47:07Z
dc.date.available2026-07-30T15:47:07Z
dc.date.issued2026-06-30
dc.description.abstractDisease tolerance limits infectious disease severity through tissue damage control mechanisms that do not target pathogens directly. Here we demonstrate that age-dependent decline in adipose tissue lipolysis compromises disease tolerance to SARS-CoV-2 infection. Young adult mice exhibited robust adipocyte lipolysis and 80% survival, whereas old mice showed impaired adipocyte lipolysis and only 20% survival. Genetic repression of adipocyte lipolysis eliminated this age-dependent survival advantage without affecting viral titers, revealing that adipocyte lipolysis is essential for disease tolerance to SARS-CoV-2 in young adults. Impaired adipocyte lipolysis in aged mice was associated with a plasma lipidomic signature that predicts COVID-19 severity and mortality in three independent human cohorts. Mechanistically, adipocyte lipolysis provides free fatty acids (FFA) to support bone marrow emergency myelopoiesis, through CD36- and CPT1-dependent FFA cellular uptake and mitochondrial import, respectively. Bone marrow derived monocytes migrate to the lung via CCL2/CCR2-dependent mechanism where they enforce an immune-metabolic communication network with parenchymal cells to sustain lung structure and function. This circuit is not required to confer protection against influenza infection, revealing pathogen-specific disease tolerance mechanisms. These findings reveal adipose tissue catabolism as a central age-dependent factor responsible for exacerbated COVID-19 mortality in aged populations. One-Sentence SummarySARS-CoV-2 infection induces adipose tissue lipolysis to release fatty acids that drive myelopoiesis and monocyte production for lung protection and COVID-19 disease tolerance, but this protective circuit declines with age, increasing disease severity in the elderly.eng
dc.identifier.doi10.64898/2026.06.27.734955
dc.identifier.other1e20377d-c7d9-45ea-b160-f5975c5467d4
dc.identifier.urihttp://hdl.handle.net/10400.14/58967
dc.language.isoeng
dc.publisherbioRxiv
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectImmunologyeng
dc.titleAge-dependent disease tolerance to SARS-CoV-2 infection
dc.typepreprint
dspace.entity.typePublication
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85

Ficheiros

Principais
A mostrar 1 - 1 de 1
Miniatura
Nome:
156587387.pdf
Tamanho:
33.89 MB
Formato:
Adobe Portable Document Format
Ver/Abrir

Coleções

CBR - Working Papers / Preprints