Dysregulation of C-X-C motif ligand 10 during aging and association with cognitive performance

被引：39

作者：

Bradburn, Steven ^{[1
]}

McPhee, Jamie ^{[1
]}

Bagley, Liam ^{[1
]}

Carroll, Michael ^{[1
]}

Slevin, Mark ^{[1
]}

Al-Shanti, Nasser ^{[1
]}

Barnouin, Yoann ^{[2
]}

Hogrel, Jean-Yves ^{[2
]}

Paasuke, Mati ^{[3
]}

Gapeyeva, Helena ^{[3
]}

Maier, Andrea ^{[4
,5
]}

Sipila, Sarianna ^{[6
]}

Narici, Marco ^{[7
]}

Robinson, Andrew ^{[8
]}

Mann, David ^{[8
]}

Payton, Antony ^{[9
]}

Pendleton, Neil ^{[8
]}

Butler-Browne, Gillian ^{[2
,3
]}

Murgatroyd, Chris ^{[1
]}

机构：

[1] Manchester Metropolitan Univ, Sch Healthcare Sci, John Dalton Bldg,Chester St, Manchester M1 5GD, Lancs, England

[2] UPMC, CNRS, INSERM, Inst Myol,UM 76,U974,UMR, Paris, France

[3] Univ Tartu, Fac Med, Inst Sport Sci & Physiotherapy, Tartu, Estonia

[4] Vrije Univ Amsterdam, Med Ctr, MOVE Res Inst, Dept Human Movement Sci, Amsterdam, Netherlands

[5] Univ Melbourne, Royal Melbourne Hosp, Dept Med & Aged Care, Melbourne, Vic, Australia

[6] Univ Jyvaskyla, Fac Sport & Hlth Sci, Gerontol Res Ctr, Jyvaskyla, Finland

[7] Univ Nottingham, Fac Med & Hlth Sci, Derby, England

[8] Univ Manchester, Sch Biol Sci, Div Neurosci & Expt Psychol, Manchester, Lancs, England

[9] Univ Manchester, Sch Hlth Sci, Ctr Epidemiol, Div Populat Hlth Hlth Serv Res & Primary Care, Manchester, Lancs, England

来源：

NEUROBIOLOGY OF AGING | 2018年 / 63卷

基金：

英国生物技术与生命科学研究理事会;

关键词：

Cognitive aging; Alzheimer's disease; Inflammaging; DNA methylation; Epigenetics; Neurodegeneration; NF-KAPPA-B; CXCL10; GENE; IFN-GAMMA; ALZHEIMERS-DISEASE; CPG METHYLATION; CELL-DEATH; IN-VITRO; EXPRESSION; AGE; POLYMORPHISMS;

D O I：

10.1016/j.neurobiolaging.2017.11.009

中图分类号：

R592 [老年病学]; C [社会科学总论];

学科分类号：

03 ; 0303 ; 100203 ;

摘要：

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. (C) 2017 The Authors. Published by Elsevier Inc.

引用

页码：54 / 64

页数：11

共 52 条

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