Fig. 1

Synergistic effects of dietary nitrate and caloric restriction on brain health. Both interventions could induce NO bioavailability through the nitrate/nitrite/NO pathway or Akt, AMPK and SIRT1 pathways. NO would increase mitochondrial efficiency by reducing ROS and inducing ATP from oxygen and ADP. In addition, NO would improve the endothelial function by interacting with sGC to convert GTP into cGMP, which activates PKG leading to MLCP (smooth muscle relaxation) and VASP (platelet aggregation inhibitor) activation. Moreover, NO could modulate inflammation that acts as pro-inflammatory when it reacts with O2- (from uncoupled mitochondria) to form ONOO-. Furthermore, NO could enhance neurotransmission through activation of the antero-and retrograding signalling, which facilitates Ca + transferal. CR and dietary nitrate have several pathways that could increase the autophagy process by mTOR inhibition, Akt, AMPK, and SIRT activation. Key: AMPK, adenosine monophosphate-activated protein kinase; Akt, protein kinase B; cGMP, cyclic guanosine monophosphate; GTP, guanosine triphosphate; MLCP, myosin light-chain phosphatase; mTOR, mechanistic target of rapamycin; PKG, protein kinase G; sGC, soluble guanylate cyclase; SIRT1 and SIRT3, sirtuin; VASP, vasodilator-stimulated phosphoprotein; XOR, xanthine-oxidoreductase