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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85037654392&origin=inward
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
C2 - 29223680
VL - 63
SP - 54
EP - 64
JO - Neurobiology of Aging
JF - Neurobiology of Aging
SN - 0197-4580
ER -