Research Paper Volume 8, Issue 11 pp 2814—2826
Caloric restriction preserves memory and reduces anxiety of aging mice with early enhancement of neurovascular functions
- 1 Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40536, USA
- 2 Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY 40536, USA
- 3 Queensland Brain Institute and Centre for Advanced Imaging, University of Queensland, Brisbane, QLD 4072, Australia
- 4 Department of Pharmaceutical Sciences, University of Kentucky, Lexington, KY 40536, USA
- 5 Department of Biomedical Engineering, University of Kentucky, Lexington, KY 40506, USA
Received: August 17, 2016 Accepted: October 15, 2016 Published: November 8, 2016
https://doi.org/10.18632/aging.101094How to Cite
Abstract
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.