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

Steven Bradburn, Jamie McPhee, Liam Bagley, Michael Carroll, Mark Slevin, Nasser Al-Shanti, Yoann Barnouin, Jean-Yves Hogrel, Mati Pääsuke, Helena Gapeyeva, Andrea Maier, Sarianna Sipilä, Marco Narici, Andrew Robinson, David Mann, Antony Payton, Neil Pendleton, Gillian Butler-Browne, Chris Murgatroyd

Research output: Contribution to journalArticleAcademicpeer-review

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.
Original languageEnglish
Pages (from-to)54-64
JournalNeurobiology of Aging
Volume63
DOIs
Publication statusPublished - 2018

Cite this

Bradburn, S., McPhee, J., Bagley, L., Carroll, M., Slevin, M., Al-Shanti, N., ... Murgatroyd, C. (2018). Dysregulation of C-X-C motif ligand 10 during aging and association with cognitive performance. Neurobiology of Aging, 63, 54-64. https://doi.org/10.1016/j.neurobiolaging.2017.11.009
Bradburn, Steven ; McPhee, Jamie ; Bagley, Liam ; Carroll, Michael ; Slevin, Mark ; Al-Shanti, Nasser ; Barnouin, Yoann ; Hogrel, Jean-Yves ; Pääsuke, Mati ; Gapeyeva, Helena ; Maier, Andrea ; Sipilä, Sarianna ; Narici, Marco ; Robinson, Andrew ; Mann, David ; Payton, Antony ; Pendleton, Neil ; Butler-Browne, Gillian ; Murgatroyd, Chris. / Dysregulation of C-X-C motif ligand 10 during aging and association with cognitive performance. In: Neurobiology of Aging. 2018 ; Vol. 63. pp. 54-64.
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title = "Dysregulation of C-X-C motif ligand 10 during aging and association with cognitive performance",
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.",
author = "Steven Bradburn and Jamie McPhee and Liam Bagley and Michael Carroll and Mark Slevin and Nasser Al-Shanti and Yoann Barnouin and Jean-Yves Hogrel and Mati P{\"a}{\"a}suke and Helena Gapeyeva and Andrea Maier and Sarianna Sipil{\"a} and Marco Narici and Andrew Robinson and David Mann and Antony Payton and Neil Pendleton and Gillian Butler-Browne and Chris Murgatroyd",
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doi = "10.1016/j.neurobiolaging.2017.11.009",
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Bradburn, S, McPhee, J, Bagley, L, Carroll, M, Slevin, M, Al-Shanti, N, Barnouin, Y, Hogrel, J-Y, Pääsuke, M, Gapeyeva, H, Maier, A, Sipilä, S, Narici, M, Robinson, A, Mann, D, Payton, A, Pendleton, N, Butler-Browne, G & Murgatroyd, C 2018, 'Dysregulation of C-X-C motif ligand 10 during aging and association with cognitive performance' Neurobiology of Aging, vol. 63, pp. 54-64. https://doi.org/10.1016/j.neurobiolaging.2017.11.009

Dysregulation of C-X-C motif ligand 10 during aging and association with cognitive performance. / Bradburn, Steven; McPhee, Jamie; Bagley, Liam; Carroll, Michael; Slevin, Mark; Al-Shanti, Nasser; Barnouin, Yoann; Hogrel, Jean-Yves; Pääsuke, Mati; Gapeyeva, Helena; Maier, Andrea; Sipilä, Sarianna; Narici, Marco; Robinson, Andrew; Mann, David; Payton, Antony; Pendleton, Neil; Butler-Browne, Gillian; Murgatroyd, Chris.

In: Neurobiology of Aging, Vol. 63, 2018, p. 54-64.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Dysregulation of C-X-C motif ligand 10 during aging and association with cognitive performance

AU - Bradburn, Steven

AU - McPhee, Jamie

AU - Bagley, Liam

AU - Carroll, Michael

AU - Slevin, Mark

AU - Al-Shanti, Nasser

AU - Barnouin, Yoann

AU - Hogrel, Jean-Yves

AU - Pääsuke, Mati

AU - Gapeyeva, Helena

AU - Maier, Andrea

AU - Sipilä, Sarianna

AU - Narici, Marco

AU - Robinson, Andrew

AU - Mann, David

AU - Payton, Antony

AU - Pendleton, Neil

AU - Butler-Browne, Gillian

AU - Murgatroyd, Chris

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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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UR - https://www.ncbi.nlm.nih.gov/pubmed/29223680

U2 - 10.1016/j.neurobiolaging.2017.11.009

DO - 10.1016/j.neurobiolaging.2017.11.009

M3 - Article

VL - 63

SP - 54

EP - 64

JO - Neurobiology of Aging

JF - Neurobiology of Aging

SN - 0197-4580

ER -