Dysregulation of C-X-C Motif Ligand 10 During Aging and Association with Cognitive Performance

Overview

Journal Neurobiol Aging

Publisher Elsevier

Specialties Geriatrics
Neurology
Physiology

Date 2017 Dec 11

PMID 29223680

Citations 23

Authors

Steven Bradburn

Jamie McPhee

Liam Bagley

Michael Carroll

Mark Slevin

Nasser Al-Shanti

Yoann Barnouin

Jean-Yves Hogrel

Mati Paasuke

Helena Gapeyeva

Andrea Maier

Sarianna Sipila

Marco Narici

Andrew Robinson

David Mann

Antony Payton

Neil Pendleton

Gillian Butler-Browne

Chris Murgatroyd

Affiliations

Soon will be listed here.

Abstract

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.

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