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

Autor: Evans F; Department of Histology and Embryology, Faculty of Medicine, UDELAR, Montevideo, Uruguay; Neuroinflammation and Gene Therapy Laboratory, Institut Pasteur de Montevideo, Montevideo, Uruguay., Alí-Ruiz D; Neuroinflammation and Gene Therapy Laboratory, Institut Pasteur de Montevideo, Montevideo, Uruguay., Rego N; Bioinformatics Unit, Institut Pasteur de Montevideo, Montevideo, Uruguay; Faculty of Sciences, UDELAR, Montevideo, Uruguay., Negro-Demontel ML; Department of Histology and Embryology, Faculty of Medicine, UDELAR, Montevideo, Uruguay; Neuroinflammation and Gene Therapy Laboratory, Institut Pasteur de Montevideo, Montevideo, Uruguay., Lago N; Neuroinflammation and Gene Therapy Laboratory, Institut Pasteur de Montevideo, Montevideo, Uruguay., Cawen FA; Neuroinflammation and Gene Therapy Laboratory, Institut Pasteur de Montevideo, Montevideo, Uruguay., Pannunzio B; Department of Histology and Embryology, Faculty of Medicine, UDELAR, Montevideo, Uruguay; Neuroinflammation and Gene Therapy Laboratory, Institut Pasteur de Montevideo, Montevideo, Uruguay., Sanchez-Molina P; Department of Cell Biology, Physiology and Immunology, and Institute of Neuroscience, Universitat Autònoma de Barcelona, Barcelona, Spain., Reyes L; Uruguayan Center for Molecular Imaging (CUDIM), Montevideo, Uruguay., Paolino A; Uruguayan Center for Molecular Imaging (CUDIM), Montevideo, Uruguay., Rodríguez-Duarte J; Laboratory of Vascular Biology and Drug Development, INDICYO Program, Institut Pasteur Montevideo, Montevideo, Uruguay., Pérez-Torrado V; Metabolic Diseases and Aging Laboratory, INDICYO Program, Institut Pasteur de Montevideo, Montevideo, Uruguay., Chicote-González A; Unitat de Bioquímica i Biologia Molecular, Departament de Biomedicina, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona (UB), Barcelona, Spain; Institut de Neurociències, Universitat de Barcelona (UB), Barcelona, Spain., Quijano C; Departamento de Bioquímica y Centro de Investigaciones Biomédicas (CEINBIO), Facultad de Medicina, Universidad de la República, Montevideo, Uruguay., Marmisolle I; Departamento de Bioquímica y Centro de Investigaciones Biomédicas (CEINBIO), Facultad de Medicina, Universidad de la República, Montevideo, Uruguay., Mulet AP; Unidad de Biotecnología en Animales de Laboratorio, Institut Pasteur de Montevideo, Montevideo, Uruguay., Schlapp G; Unidad de Biotecnología en Animales de Laboratorio, Institut Pasteur de Montevideo, Montevideo, Uruguay., Meikle MN; Unidad de Biotecnología en Animales de Laboratorio, Institut Pasteur de Montevideo, Montevideo, Uruguay., Bresque M; Metabolic Diseases and Aging Laboratory, INDICYO Program, Institut Pasteur de Montevideo, Montevideo, Uruguay., Crispo M; Unidad de Biotecnología en Animales de Laboratorio, Institut Pasteur de Montevideo, Montevideo, Uruguay., Savio E; Uruguayan Center for Molecular Imaging (CUDIM), Montevideo, Uruguay., Malagelada C; Unitat de Bioquímica i Biologia Molecular, Departament de Biomedicina, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona (UB), Barcelona, Spain; Institut de Neurociències, Universitat de Barcelona (UB), Barcelona, Spain., Escande C; Metabolic Diseases and Aging Laboratory, INDICYO Program, Institut Pasteur de Montevideo, Montevideo, Uruguay., Peluffo H; Department of Histology and Embryology, Faculty of Medicine, UDELAR, Montevideo, Uruguay; Neuroinflammation and Gene Therapy Laboratory, Institut Pasteur de Montevideo, Montevideo, Uruguay; Unitat de Bioquímica i Biologia Molecular, Departament de Biomedicina, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona (UB), Barcelona, Spain; Institut de Neurociències, Universitat de Barcelona (UB), Barcelona, Spain. Electronic address: hugo.peluffo@ub.edu.
Jazyk: angličtina
Zdroj: Cell reports [Cell Rep] 2023 Oct 31; Vol. 42 (10), pp. 113269.
DOI: 10.1016/j.celrep.2023.113269
Abstrakt: 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 18 FDG 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.
Competing Interests: Declaration of interests The authors declare no competing interests.
(Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE