Calorie Restriction Reduces the Influence of Glucoregulatory Dysfunction on Regional Brain Volume in Aged Rhesus Monkeys

  1. Sterling C. Johnson1,2,3,4,6
  1. 1Geriatric Research Education and Clinical Center, William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin
  2. 2Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin-Madison, Madison, Wisconsin
  3. 3Wisconsin Alzheimer’s Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
  4. 4Wisconsin National Primate Research Center, Madison, Wisconsin
  5. 5Department of Radiology, University of Wisconsin-Madison, Madison, Wisconsin
  6. 6Neuroscience Training Program, University of Wisconsin-Madison, Madison, Wisconsin
  7. 7Department of Biostatistics, University of Alabama at Birmingham, Birmingham, Alabama
  8. 8Department of Neurobiology and Anatomy Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina
  9. 9Department of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
  10. 10Institute for Clinical and Translational Research, University of Wisconsin-Madison, Madison, Wisconsin
  1. Corresponding author: Sterling C. Johnson, scj{at}


Insulin signaling dysregulation is related to neural atrophy in hippocampus and other areas affected by neurovascular and neurodegenerative disorders. It is not known if long-term calorie restriction (CR) can ameliorate this relationship through improved insulin signaling or if such an effect might influence task learning and performance. To model this hypothesis, magnetic resonance imaging was conducted on 27 CR and 17 control rhesus monkeys aged 19–31 years from a longitudinal study. Voxel-based regression analyses were used to associate insulin sensitivity with brain volume and microstructure cross-sectionally. Monkey motor assessment panel (mMAP) performance was used as a measure of task performance. CR improved glucoregulation parameters and related indices. Higher insulin sensitivity predicted more gray matter in parietal and frontal cortices across groups. An insulin sensitivity × dietary condition interaction indicated that CR animals had more gray matter in hippocampus and other areas per unit increase relative to controls, suggesting a beneficial effect. Finally, bilateral hippocampal volume adjusted by insulin sensitivity, but not volume itself, was significantly associated with mMAP learning and performance. These results suggest that CR improves glucose regulation and may positively influence specific brain regions and at least motor task performance. Additional studies are warranted to validate these relationships.

  • Received September 8, 2011.
  • Accepted January 11, 2012.

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