Caloric restriction preserves memory and reduces anxiety of aging mice with early enhancement of neurovascular functions

Ishita Parikh, Janet Guo, Kai Hsiang Chuang, Yu Zhong, Ralf G. Rempe, Jared D. Hoffman, Rachel Armstrong, Björn Bauer, Anika M.S. Hartz, Ai Ling Lin

Research output: Contribution to journalArticlepeer-review

57 Scopus citations


Neurovascular integrity plays an important role in protecting cognitive and mental health in aging. Lifestyle interventions that sustain neurovascular integrity may thus be critical on preserving brain functions in aging and reducing the risk for age-related neurodegenerative disorders. Here we show that caloric restriction (CR) had an early effect on neurovascular enhancements, and played a critical role in preserving vascular, cognitive and mental health in aging. In particular, we found that CR significantly enhanced cerebral blood flow (CBF) and blood-brain barrier function in young mice at 5-6 months of age. The neurovascular enhancements were associated with reduced mammalian target of rapamycin expression, elevated endothelial nitric oxide synthase signaling, and increased ketone bodies utilization. With age, CR decelerated the rate of decline in CBF. The preserved CBF in hippocampus and frontal cortex were highly correlated with preserved memory and learning, and reduced anxiety, of the aging mice treated with CR (18-20 months of age). Our results suggest that dietary intervention started in the early stage (e.g., young adults) may benefit cognitive and mental reserve in aging. Understanding nutritional effects on neurovascular functions may have profound implications in human brain aging and age-related neurodegenerative disorders.

Original languageEnglish
Pages (from-to)2814-2826
Number of pages13
Issue number11
StatePublished - 2016

Bibliographical note

Funding Information:
We thank Vikas Bakshi, David Powell, Stephanie Edelmann, Shin-ichi Akanuma, and Harrison Tam for their technical assistance. We also thank Dr. Adam Bachstetter for his advice on behavioral assessments. The MRI imaging and data were processed using MANGO software developed by the Research Imaging Institute of the University of Texas Health Science Center at San Antonio. This research was supported by National Institute of Health (NIH) Grant K01AG040164 and American Federation for Aging Research Grant #A12474 to ALL, and NIH R01AG039621 to AMSH. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The 7T ClinScan small animal MRI scanner of the University of Kentucky was funded by the S10 NIH Shared Instrumentation Program Grant (1S10RR029541-01).


  • Anxiety
  • Blood-brain barrier
  • Caloric restriction
  • Cerebral blood flow
  • Cognition
  • Magnetic resonance imaging (MRI)
  • Mammalian target of rapamcyin (mTOR)

ASJC Scopus subject areas

  • Aging
  • Cell Biology


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