Caloric restriction preserves memory and reduces anxiety of aging mice with early enhancement of neurovascular functions.
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.
Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40536, USA.|Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY 40536, USA.
Ishita
I
Parikh
Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40536, USA.
Janet
J
Guo
Queensland Brain Institute and Centre for Advanced Imaging, University of Queensland, Brisbane, QLD 4072, Australia.
Kai-Hsiang
KH
Chuang
Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40536, USA.
Yu
Y
Zhong
Department of Pharmaceutical Sciences, University of Kentucky, Lexington, KY 40536, USA.
Ralf G
RG
Rempe
Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40536, USA.|Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY 40536, USA.
Jared D
JD
Hoffman
Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40536, USA.
Rachel
R
Armstrong
Department of Pharmaceutical Sciences, University of Kentucky, Lexington, KY 40536, USA.
Björn
B
Bauer
Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40536, USA.|Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY 40536, USA.
Anika M S
AM
Hartz
Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40536, USA.|Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY 40536, USA.|Department of Biomedical Engineering, University of Kentucky, Lexington, KY 40506, USA.
Ai-Ling
AL
Lin
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001007:Anxiety / Q000378:metabolism*; D001522:Behavior, Animal / Q000502:physiology; D001812:Blood-Brain Barrier / Q000378:metabolism*; D031204:Caloric Restriction; D002560:Cerebrovascular Circulation / Q000502:physiology*; D003071:Cognition / Q000502:physiology; D005625:Frontal Lobe / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D008568:Memory / Q000502:physiology*; D051379:Mice; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D052250:Nitric Oxide Synthase Type III
anxiety; blood-brain barrier; caloric restriction; cerebral blood flow; cognition; magnetic resonance imaging (MRI); mammalian target of rapamcyin (mTOR)