CD300f immune receptor contributes to healthy aging by regulating inflammaging, metabolism, and cognitive decline
Evans, Frances (Instituto Pasteur de Montevideo)
Alí-Ruiz, Daniela (Instituto Pasteur de Montevideo)
Rego, Natalia (Instituto Pasteur de Montevideo)
Negro-Demontel, Maria Luciana (Instituto Pasteur de Montevideo)
Lago, Natalia (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Cawen, Fabio Andrés (Instituto Pasteur de Montevideo)
Pannunzio, Bruno (Instituto Pasteur de Montevideo)
Sanchez-Molina, Paula (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Reyes, Laura (Centro Uruguayo de Imagenología Molecular)
Paolino, Andrea (Centro Uruguayo de Imagenología Molecular)
Rodríguez-Duarte, Jorge (Instituto Pasteur de Montevideo)
Pérez-Torrado, Valentina (Instituto Pasteur de Montevideo)
Chicote-González, Almudena (Universitat de Barcelona. Departament de Biomedicina)
Quijano, Celia (Universidad de la República. Departamento de Bioquímica (Montevideo, Uruguay))
Marmisolle, Inés (Universidad de la República. Departamento de Bioquímica (Montevideo, Uruguay))
Mulet, Ana Paula (Instituto Pasteur de Montevideo)
Schlapp, Geraldine (Instituto Pasteur de Montevideo)
Meikle, Maria Noel (Instituto Pasteur de Montevideo)
Bresque, Mariana (Instituto Pasteur de Montevideo)
Crispo, Martina (Instituto Pasteur de Montevideo)
Savio, Eduardo (Centro Uruguayo de Imagenología Molecular)
Malagelada, Cristina (Universitat de Barcelona. Departament de Biomedicina)
Escande, Carlos (Instituto Pasteur de Montevideo)
Peluffo, Hugo (Instituto Pasteur de Montevideo)
Universitat Autònoma de Barcelona. Institut de Neurociències

Date:	2023
Abstract:	Emerging evidence suggests that immune receptors may participate in many aging-related processes such as energy metabolism, inflammation, and cognitive decline. CD300f, a TREM2-like lipid-sensing immune receptor, is an exceptional receptor as it integrates activating and inhibitory cell-signaling pathways that modulate inflammation, efferocytosis, and microglial metabolic fitness. We hypothesize that CD300f can regulate systemic aging-related processes and ultimately healthy lifespan. We closely followed several cohorts of two strains of CD300f-/- and WT mice of both sexes for 30 months and observed an important reduction in lifespan and healthspan in knockout mice. This was associated with systemic inflammaging, increased cognitive decline, reduced brain glucose uptake observed by 18FDG PET scans, enrichment in microglial aging/neurodegeneration phenotypes, proteostasis alterations, senescence, increased frailty, and sex-dependent systemic metabolic changes. Moreover, the absence of CD300f altered macrophage immunometabolic phenotype. Taken together, we provide strong evidence suggesting that myeloid cell CD300f immune receptor contributes to healthy aging.
Grants:	European Commission. Horizon 2020 101030280 Agencia Estatal de Investigación PID2021-123272OB-I00
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Aging ; Microgial ; DAM ; Macrophage ; Immunometabolism ; Cognitive decline ; Dementia ; Positron emmission tomogrraphy ; Glucose metabolism ; Inflammaging ; Healthspan ; Lifespan ; Sex differences
Published in:	Cell reports, Vol. 42 Núm. 10 (2023) , p. 113269, ISSN 2211-1247

DOI: 10.1016/j.celrep.2023.113269
PMID: 37864797

24 p, 6.3 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Neurociències (INc)
Articles > Research articles
Articles > Published articles