CD300f immune receptor contributes to healthy aging by regulating inflammaging, metabolism, and cognitive decline

Autor: Frances Evans, Daniela Alí-Ruiz, Natalia Rego, María Luciana Negro-Demontel, Natalia Lago, Fabio Andrés Cawen, Bruno Pannunzio, Paula Sanchez-Molina, Laura Reyes, Andrea Paolino, Jorge Rodríguez-Duarte, Valentina Pérez-Torrado, Almudena Chicote-González, Celia Quijano, Inés Marmisolle, Ana Paula Mulet, Geraldine Schlapp, María Noel Meikle, Mariana Bresque, Martina Crispo, Eduardo Savio, Cristina Malagelada, Carlos Escande, Hugo Peluffo
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Cell Reports, Vol 42, Iss 10, Pp 113269- (2023)
Druh dokumentu: article
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2023.113269
Popis: Summary: 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.
Databáze: Directory of Open Access Journals