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

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 mot...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5805841/
https://www.ncbi.nlm.nih.gov/pubmed/29223680
http://dx.doi.org/10.1016/j.neurobiolaging.2017.11.009
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author 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
author_facet 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
author_sort Bradburn, Steven
collection PubMed
description 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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spelling pubmed-58058412018-03-01 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 Neurobiol Aging Article 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. Elsevier 2018-03 /pmc/articles/PMC5805841/ /pubmed/29223680 http://dx.doi.org/10.1016/j.neurobiolaging.2017.11.009 Text en © 2017 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
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
title Dysregulation of C-X-C motif ligand 10 during aging and association with cognitive performance
title_full Dysregulation of C-X-C motif ligand 10 during aging and association with cognitive performance
title_fullStr Dysregulation of C-X-C motif ligand 10 during aging and association with cognitive performance
title_full_unstemmed Dysregulation of C-X-C motif ligand 10 during aging and association with cognitive performance
title_short Dysregulation of C-X-C motif ligand 10 during aging and association with cognitive performance
title_sort dysregulation of c-x-c motif ligand 10 during aging and association with cognitive performance
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5805841/
https://www.ncbi.nlm.nih.gov/pubmed/29223680
http://dx.doi.org/10.1016/j.neurobiolaging.2017.11.009
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