NOS3 and Anxiety: In this study, we demonstrate (i) in young mice, CR enhanced CBF and BBB function, (ii) inhibited mTOR, which was associated with increased eNOS, reduced glucose metabolism, and increased blood ketone level; (iii) in the aging mice, CR preserved CBF, learning, long-term memory, and reduced anxiety; (iv) hippocampal and frontal CBF exhibited high association with cognitive performance and inversely correlated with anxiety level.