Age-related changes in neural volume and microstructure associated with interleukin-6 are ameliorated by a calorie-restricted diet in old rhesus monkeys
Open accessAbstract
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-6xCR 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.
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Caloric restriction-associated reversal of aging-induced brain atrophy was also associated with reduced IL-6 levels, thus highlighting the role of immune mediators.
“Furthermore, caloric restriction-associated reversal of aging-induced brain atrophy was also associated with reduced IL-6 levels, thus highlighting the role of immune mediators (Willette et al, 2010).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Willette et al, 2010
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- Authors
- Willette, A. A., Bendlin, B. B., McLaren, D. G., Canu, E., Kastman, E. K., Kosmatka, K. J., Xu, G., Field, A. S., Alexander, A. L., Colman, R. J., Weindruch, R. H., Coe, C. L., & Johnson, S. C.
- Affiliations
- University of Wisconsin–Madison (US)
- William S. Middleton Memorial Veterans Hospital (US)
- Corresponding author
- Johnson, S.C.
- ORCID
- Venue
- NeuroImage
- Publisher
- Elsevier BV
- Published
- 2010-07
- Volume
- 51
- Issue
- 3
- Pages
- 987-994
- ISSN
- 1053-8119 (ISSN-L)
- PMC
- PMC2877377
- OpenAlex
- W2017502139
- Cited by
- 55
- References
- 82
- Citations by year
- 2026: 1 · 2025: 2 · 2022: 3 · 2021: 5 · 2020: 3 · 2019: 2 · 2018: 4 · 2017: 1 · 2016: 7 · 2015: 1 · 2014: 1 · 2013: 7 · 2012: 4
- FWCI
- 4.85
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- NeuroImage (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (RR000167, AG011915, AG000213, GM007507, MH085051, MH062015)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- interleukin-6, caloric restriction, brain aging, gray matter volume, white matter microstructure, fractional anisotropy, mean diffusivity, corpus callosum, inflammatory cytokines, rhesus monkeys, neuroinflammation, dietary intervention
- MeSH terms
- Aging, Animals, Brain, Female, Interleukins, Macaca mulatta, Magnetic Resonance Imaging, Male, Organ Size, Interleukin-6, Caloric Restriction
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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