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

NEUROBIOLOGY OF AGING

卷:63

Article

Bradburn, Steven¹  McPhee, Jamie¹  Bagley, Liam¹  Carroll, Michael¹  Slevin, Mark¹  Al-Shanti, Nasser¹  Barnouin, Yoann²  Hogrel, Jean-Yves²  Paasuke, Mati³  Gapeyeva, Helena³  Maier, Andrea^4,5  Sipila, Sarianna⁶  Narici, Marco⁷  Robinson, Andrew⁸  Mann, David⁸  Payton, Antony⁹  Pendleton, Neil⁸  Butler-Browne, Gillian^2,3  Murgatroyd, Chris¹ 

[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

关键词: Cognitive aging;    Alzheimer's disease;    Inflammaging;    DNA methylation;    Epigenetics;    Neurodegeneration;   

DOI  :  10.1016/j.neurobiolaging.2017.11.009

来源: Elsevier

【 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.

【 授权许可】

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