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

Evan, Frances - Alí-Ruiz, Daniela - Rego, Natalia - Negro-Demontel, María Luciana - Lago, Natalia - Cawen, Fabio Andrés - Pannunzio, Bruno - Sanchez-Molina, Paula - Reyes, Laura - Paolino, Andrea - Rodríguez-Duarte, Jorge - Pérez-Torrado, Valentina - Chicote-González, Almudena - Quijano, Celia - Marmisolle, Inés - Mulet, Ana Paula - Schlapp, Geraldine - Meikle, María Noel - Bresque, Mariana - Crispo, Martina - Savio, Eduardo - Malagelada, Cristina - Escande, Carlos - Peluffo, Hugo

Resumen:

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.

Detalles Bibliográficos
2023
CP: Immunology
CP: Metabolism
DAM
Aging
Cognitive decline
Dementia
Glucose metabolism
Healthspan
Immunometabolism
Inflammaging
Lifespan
Macrophage
Microglia
Positron emmission tomography
Sex differences
ANIMALES
DISFUNCIÓN COGNITIVA
METABOLISMO
MUJERES
ENVEJECIMIENTO SALUDABLE
HOMBRES
MACRÓFAGOS
INFLAMACIÓN
RATONES NOQUEADOS
MICROGLÍA
Inglés
Universidad de la República
COLIBRI
https://hdl.handle.net/20.500.12008/52592
Acceso abierto
Licencia Creative Commons Atribución (CC - By 4.0)