Dysregulation of C-X-C motif ligand 10 during aging and association with cognitive performance
2018
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
CXCL10gene promoter. In vitro analysis supported the role of DNA methylation in regulating
CXCL10transcription. A polymorphism (rs56061981) that altered methylation at one of these
CpG sitesfurther associated with working memory performance in 2 independent aging cohorts. Studying prefrontal cortex samples, we found higher
CXCL10protein 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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