Cell Reports (Oct 2023)
CD300f immune receptor contributes to healthy aging by regulating inflammaging, metabolism, and cognitive decline
- 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
Affiliations
- Frances Evans
- Department of Histology and Embryology, Faculty of Medicine, UDELAR, Montevideo, Uruguay; Neuroinflammation and Gene Therapy Laboratory, Institut Pasteur de Montevideo, Montevideo, Uruguay
- Daniela Alí-Ruiz
- Neuroinflammation and Gene Therapy Laboratory, Institut Pasteur de Montevideo, Montevideo, Uruguay
- Natalia Rego
- Bioinformatics Unit, Institut Pasteur de Montevideo, Montevideo, Uruguay; Faculty of Sciences, UDELAR, Montevideo, Uruguay
- María Luciana Negro-Demontel
- Department of Histology and Embryology, Faculty of Medicine, UDELAR, Montevideo, Uruguay; Neuroinflammation and Gene Therapy Laboratory, Institut Pasteur de Montevideo, Montevideo, Uruguay
- Natalia Lago
- Neuroinflammation and Gene Therapy Laboratory, Institut Pasteur de Montevideo, Montevideo, Uruguay
- Fabio Andrés Cawen
- Neuroinflammation and Gene Therapy Laboratory, Institut Pasteur de Montevideo, Montevideo, Uruguay
- Bruno Pannunzio
- Department of Histology and Embryology, Faculty of Medicine, UDELAR, Montevideo, Uruguay; Neuroinflammation and Gene Therapy Laboratory, Institut Pasteur de Montevideo, Montevideo, Uruguay
- Paula Sanchez-Molina
- Department of Cell Biology, Physiology and Immunology, and Institute of Neuroscience, Universitat Autònoma de Barcelona, Barcelona, Spain
- Laura Reyes
- Uruguayan Center for Molecular Imaging (CUDIM), Montevideo, Uruguay
- Andrea Paolino
- Uruguayan Center for Molecular Imaging (CUDIM), Montevideo, Uruguay
- Jorge Rodríguez-Duarte
- Laboratory of Vascular Biology and Drug Development, INDICYO Program, Institut Pasteur Montevideo, Montevideo, Uruguay
- Valentina Pérez-Torrado
- Metabolic Diseases and Aging Laboratory, INDICYO Program, Institut Pasteur de Montevideo, Montevideo, Uruguay
- Almudena Chicote-González
- 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
- Celia Quijano
- Departamento de Bioquímica y Centro de Investigaciones Biomédicas (CEINBIO), Facultad de Medicina, Universidad de la República, Montevideo, Uruguay
- Inés Marmisolle
- Departamento de Bioquímica y Centro de Investigaciones Biomédicas (CEINBIO), Facultad de Medicina, Universidad de la República, Montevideo, Uruguay
- Ana Paula Mulet
- Unidad de Biotecnología en Animales de Laboratorio, Institut Pasteur de Montevideo, Montevideo, Uruguay
- Geraldine Schlapp
- Unidad de Biotecnología en Animales de Laboratorio, Institut Pasteur de Montevideo, Montevideo, Uruguay
- María Noel Meikle
- Unidad de Biotecnología en Animales de Laboratorio, Institut Pasteur de Montevideo, Montevideo, Uruguay
- Mariana Bresque
- Metabolic Diseases and Aging Laboratory, INDICYO Program, Institut Pasteur de Montevideo, Montevideo, Uruguay
- Martina Crispo
- Unidad de Biotecnología en Animales de Laboratorio, Institut Pasteur de Montevideo, Montevideo, Uruguay
- Eduardo Savio
- Uruguayan Center for Molecular Imaging (CUDIM), Montevideo, Uruguay
- Cristina Malagelada
- 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
- Carlos Escande
- Metabolic Diseases and Aging Laboratory, INDICYO Program, Institut Pasteur de Montevideo, Montevideo, Uruguay
- Hugo Peluffo
- 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; Corresponding author
- Journal volume & issue
-
Vol. 42,
no. 10
p. 113269
Abstract
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.
