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RESEARCH PRODUCT
Dysregulation of C-X-C motif ligand 10 during aging and association with cognitive performance
Jean-yves HogrelGillian Butler-browneLiam BagleySteven BradburnNasser Al-shantiChris MurgatroydDavid M. A. MannNeil PendletonMarco NariciMati PääsukeAndrew C RobinsonYoann BarnouinMichael C. CarrollAntony PaytonHelena GapeyevaSarianna SipiläMark SlevinJamie S. McpheeAndrea B. Maiersubject
0301 basic medicinegamma interferon inducible protein 10genomic DNAAlzheimerin tautiEpigenesis GeneticCohort StudiesCXCL10 geneCognitionsingle nucleotide polymorphismcognitive defectCognitive declineAged 80 and overCerebral Cortexeducation.field_of_studyprefrontal cortexDNA methylationGeneral NeuroscienceadultNeurodegenerationneurodegenerationta3141U937 CellsMethylationta3142Alzheimer's diseasecohort analysisDNA-metylaatioagedfemalepriority journalepigenetiikkaDNA methylationAlzheimer's diseaseAlzheimer diseasetranscription regulationAlzheimer’s diseasekognitiiviset taidotmedicine.medical_specialty[SDV.MHEP.AHA] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO]in vitro studyAdolescentheredityPopulationBiologyArticleworking memoryYoung Adult03 medical and health sciencesCognitive agingpromoter regionmaleMemoryInternal medicineJournal Articlemedicine[SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO]HumansCXCL10controlled studyEpigeneticshumanbrain levelNeurodegenerationeducationepigeneticscognitive aginghuman cellagingdisease associationmedicine.diseasemajor clinical studyInflammagingChemokine CXCL10gamma interferon inducible protein 10; genomic DNA adult; age; aged; aging; Alzheimer disease; Article; brain level; cognitive defect; cohort analysis; controlled study; CpG island; CXCL10 gene; disease association; DNA methylation; epigenetics; female; heredity; human; human cell; in vitro study; inflammation; major clinical study; male; prefrontal cortex; priority journal; promoter region; single nucleotide polymorphism; transcription regulation; working memory; Alzheimer's disease; Cognitive aging; DNA methylation; Epigenetics; Inflammaging; Neurodegeneration030104 developmental biologyEndocrinologyikääntyminenageinflammationNerve DegenerationCpG islandinflammagingNeurology (clinical)Geriatrics and GerontologyHeLa CellsDevelopmental Biologydescription
International audience; Chronic low-grade inflammation during aging (inflammaging) is associated with cognitive decline and neurodegeneration; however, the mechanisms underlying inflammaging are unclear. We studied a population (n = 361) of healthy young and old adults from the MyoAge cohort. Peripheral levels of C-X-C motif chemokine ligand 10 (CXCL10) was found to be higher in older adults, compared with young, and negatively associated with working memory performance. This coincided with an age-related reduction in blood DNA methylation at specific CpGs within the CXCL10 gene promoter. In vitro analysis supported the role of DNA methylation in regulating CXCL10 transcription. A polymorphism (rs56061981) that altered methylation at one of these CpG sites further associated with working memory performance in 2 independent aging cohorts. Studying prefrontal cortex samples, we found higher CXCL10 protein levels in those with Alzheimer's disease, compared with aged controls. These findings support the association of peripheral inflammation, as demonstrated by CXCL10, in aging and cognitive decline. We reveal age-related epigenetic and genetic factors which contribute to the dysregulation of CXCL10.
year | journal | country | edition | language |
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2017-11-23 | Neurobiology of Aging |