Homocysteine, neural atrophy, and the effect of caloric restriction in rhesus monkeys

Auriel A. Willette, Catherine Gallagher, Barbara B. Bendlin, Donald G. McLaren, Erik K. Kastman, Elisa Canu, Kris J. Kosmatka, Aaron S. Field, Andrew L. Alexander, Ricki J. Colman, Mary Lou L Voytko, Richard H. Weindruch, Christopher L. Coe, Sterling C. Johnson

Research output: Contribution to journalArticlepeer-review


Higher serum homocysteine (Hcy) levels in humans are associated with vascular pathology and greater risk for dementia, as well as lower global and regional volumes in frontal lobe and hippocampus. Calorie restriction (CR) in rhesus monkeys (Macaca mulatta) may confer neural protection against age- or Hcy-related vascular pathology. Hcy was collected proximal to a magnetic resonance imaging (MRI) acquisition in aged rhesus monkeys and regressed against volumetric and diffusion tensor imaging indexes using voxel-wise analyses. Higher Hcy was associated with lower white matter volume in pons and corpus callosum. Hcy was correlated with lower gray matter volume and density in prefrontal cortices and striatum. CR did not influence Hcy levels. However, control monkeys exhibited a strong negative correlation between Hcy and global gray matter, whereas no relationship was evident for the CR monkeys. Similar group differences were also seen across modalities in the splenium of the corpus callosum, prefrontal cortices, hippocampus, and somatosensory areas. The data suggest that CR may ameliorate the influence of Hcy on several important age-related parameters of parenchymal health.

Original languageEnglish
Pages (from-to)670-680
Number of pages11
JournalNeurobiology of Aging
Issue number4
Publication statusPublished - Apr 2012


  • Aging
  • Caloric restriction
  • Diffusion tensor imaging
  • Homocysteine
  • Neural atrophy
  • Primate
  • Rhesus monkey
  • Voxel-based morphometry

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Ageing
  • Developmental Biology
  • Geriatrics and Gerontology


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