Age-related changes in neural volume and microstructure associated with interleukin-6 are ameliorated by a calorie-restricted diet in old rhesus monkeys

A. A. Willette, B. B. Bendlin, D. G. McLaren, E. Canu, E. K. Kastman, K. J. Kosmatka, G. Xu, A. S. Field, A. L. Alexander, R. J. Colman, R. H. Weindruch, C. L. Coe, S. C. Johnson

Research output: Contribution to journalArticle

Abstract

Systemic levels of proinflammatory cytokines such as interleukin-6 (IL-6) increase in old age and may contribute to neural atrophy in humans. We investigated IL-6 associations with age in T1-weighted segments and microstructural diffusion indices using MRI in aged rhesus monkeys (Macaca mulatta). Further, we determined if long-term 30% calorie restriction (CR) reduced IL-6 and attenuated its association with lower tissue volume and density. Voxel-based morphometry (VBM) and diffusion-weighted voxelwise analyses were conducted. IL-6 was associated with less global gray and white matter (GM and WM), as well as smaller parietal and temporal GM volumes. Lower fractional anisotropy (FA) was associated with higher IL-6 levels along the corpus callosum and various cortical and subcortical tracts. Higher IL-6 concentrations across subjects were also associated with increased mean diffusivity (MD) throughout many brain regions, particularly in corpus callosum, cingulum, and parietal, frontal, and prefrontal areas. CR monkeys had significantly lower IL-6 and less associated atrophy. An IL-6 × CR interaction across modalities also indicated that CR mitigated IL-6 related changes in several brain regions compared to controls. Peripheral IL-6 levels were correlated with atrophy in regions sensitive to aging, and this relationship was decreased by CR.

Original languageEnglish
Pages (from-to)987-994
Number of pages8
JournalNeuroImage
Volume51
Issue number3
DOIs
Publication statusPublished - Jul 2010

Keywords

  • Aging
  • Atrophy
  • Calorie restriction
  • Interleukin-6
  • Monkey
  • Voxel-based morphometry

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Neurology

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