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

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 pa...

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Main Author: Evans Isola, Frances (author)
Other Authors: Alí Ruiz, Daniela (author), Rego, Natalia (author), Negro Demontel, María Luciana (author), Lago, Natalia (author), Cawen Curbelo, Fabio Andrés (author), Pannunzio, Bruno (author), Sánchez-Molina, Paula (author), Reyes Ábalos, Ana Laura (author), Paolino, Andrea (author), Rodríguez Duarte, Jorge (author), Pérez Torrado, María Valentina (author), Chicote-González, Almudena (author), Quijano, Celia (author), Marmisolle, Inés (author), Mulet, Ana Paula (author), Schlapp, Geraldine (author), Meikle, María Noel (author), Bresque, Mariana (author), Crispo, Martina (author), Savio, Eduardo (author), Malagelada, Cristina (author), Escande, Carlos (author), Peluffo, Hugo (author)
Format: article
Language:English
Published: 2023
Subjects:
Aging
Microglia
DAM
Macrophage
Immunometabolism
Cognitive decline
Dementia
Positron emmission tomography
Glucose metabolism
Inflammaging
Healthspan
Lifespan
Sex differences
Online Access:https://hdl.handle.net/20.500.12008/43331
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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.

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