Dysregulation of CXC motif ligand 10 during aging and association with cognitive performance

Bradburn, Steven, McPhee, Jamie ORCID: https://orcid.org/0000-0002-3659-0773, Bagley, Liam ORCID: https://orcid.org/0000-0001-5538-0870, Carroll, Michael, Slevin, Mark ORCID: https://orcid.org/0000-0003-3767-4861, Al-Shanti, Nasser, Barnouin, Yoann, Hogrel, Jean-Yves, Paasuke, Mati, Gapeyeva, Helena, Maier, Andrea, Sipila, Sarianna, Narici, Marco, Robinson, Andrew, Mann, David, Payton, Antony, Pendleton, Neil, Butler-Browne, Gillian and Murgatroyd, Chris ORCID: https://orcid.org/0000-0002-6885-7794 (2018) Dysregulation of CXC motif ligand 10 during aging and association with cognitive performance. Neurobiology of Aging, 63. pp. 54-64. ISSN 0197-4580

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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 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 two independent aging cohorts. Studying prefrontal cortex samples, we found higher CXCL10 protein levels in those with Alzheimer’s disease, compared to 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.