Aging, Environment, & DiseaseDNA Methylation and Hydroxymethylation

Age-related Dysregulation of Cytokine CXCL10 is Linked to Cognitive Decline

Bradburn 2018Chronic inflammation is a hallmark of aging pathology [1], [2]. Chronic inflammation is a risk factor for decreased cognitive performance [3], [4] and dementia [5] in older populations. Bradborn et al analyzed 35 cytokines in humans from the MyoAge study [6] to determine which are important for cognitive decline and how their regulation changes with age.

Of the 35 cytokines analyzed, only CXCL10, eotaxin-1, and IL-6 were significantly related to age when accounting for gender, location and other confounding variables. After further analysis, only CXCL10 was significantly associated with spatial working memory. Average CpG methylation in the proximal CXCL10 promoter was negatively correlated with age. The authors tested all of the CpG methylation sites in the proximal promoter and found that only CpG-168 methylation correlated with CXCL10 plasma protein levels.

Bradborn et al next looked at whether methylation of the CXCL10 proximal promoter and spatial memory are linked. The authors used the rs56061981 mouse genotype with a mutation causing lower methylation at the proximal promoter. Rs56061981 mice have higher spatial working memory scores than control mice, in older animals. When analyzing humans, there was no significant difference in methylation of the CXCL10 proximal promoter between Alzheimer’s disease and control samples. On the other hand, CXCL10 protein levels were higher in the prefrontal cortex of Alzheimer’s disease samples than controls in humans.

The above research found that the cytokine CXCL10 is negatively related to spatial working memory performance in aged humans. Increased CXCL10 levels were also seen in the prefrontal cortex of intermediate AD patients, compared to aged controls. No decrease in CXCL10 promoter methylation in prefrontal cortex suggests that increased CXCL10 protein levels are independent of promoter methylation.

 

Original Article

  1. Bradburn et al., “Dysregulation of C-X-C motif ligand 10 during aging and association with cognitive performance.,” Neurobiol. Aging, vol. 63, pp. 54–64, Mar. 2018.

References

  1. D. Baylis, D. B. Bartlett, H. P. Patel, and H. C. Roberts, “Understanding how we age: insights into inflammaging.,” Longevity & healthspan, vol. 2, no. 1, p. 8, May 2013.
  2. C. Franceschi and J. Campisi, “Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases.,” journals Gerontol. Ser. Biol. Sci. Med. Sci., vol. 69 Suppl 1, pp. S4–S9, Jun. 2014.
  3. B. BT et al., “Association between IL-8 cytokine and cognitive performance in an elderly general population–the MEMO-Study.,” Neurobiol. Aging, vol. 29, Jun. 2008.
  4. J. N. Trollor et al., “The association between systemic inflammation and cognitive performance in the elderly: the Sydney Memory and Ageing Study.,” Age (Dordrecht, Netherlands), vol. 34, no. 5, pp. 1295–1308, Oct. 2012.
  5. A. Koyama, J. O’Brien, J. Weuve, D. Blacker, A. L. Metti, and K. Yaffe, “The role of peripheral inflammatory markers in dementia and Alzheimer’s disease: a meta-analysis.,” journals Gerontol. Ser. Biol. Sci. Med. Sci., vol. 68, no. 4, pp. 433–440, Apr. 2013.
  6. J. S. McPhee et al., “Physiological and functional evaluation of healthy young and older men and women: design of the European MyoAge study.,” Biogerontology, vol. 14, no. 3, pp. 325–337, Jul. 2013.
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Aaron Barnett

Aaron Barnett