Brain NAD Is Associated With ATP Energy Production

The analysis revealed that brain NAD level and NAD+/NADH redox ratio were positively associated with ATP level and the rate of energy production, respectively. Moreover, a metabolic network linking NAD with membrane phospholipid metabolism, energy production, and aging was identified. An inverted trend between age and NAD level was detected.

Brain NAD Is Associated With ATP Energy Production

Brain NAD Is Associated With ATP Energy Production and Membrane Phospholipid Turnover in Humans

The brain requires a large amount of energy, mostly derived from the metabolism of glucose, which decreases substantially with age and neurological diseases. While mounting evidence in model organisms illustrates the central role of brain nicotinamide adenine dinucleotide (NAD) for maintaining energy homeostasis, similar data are sparse in humans. This study explores the correlations between brain NAD, energy production and membrane phospholipid metabolism by 31-phosphorous magnetic resonance spectroscopy (31P-MRS) across 50 healthy participants including a young (mean age 27.1-year-old) and middle-aged (mean age 56.4-year-old) group. The analysis revealed that brain NAD level and NAD+/NADH redox ratio were positively associated with ATP level and the rate of energy production, respectively. Moreover, a metabolic network linking NAD with membrane phospholipid metabolism, energy production, and aging was identified. An inverted trend between age and NAD level was detected. These results pave the way for the use of 31P-MRS as a powerful non-invasive tool to support the development of new therapeutic interventions targeting NAD associated phospho-metabolic pathways in brain aging and neurological diseases.

Based on extensive in-vitro and animal data, one would predict that aging and many neurological diseases would lead to a decrease in brain total NAD (tNAD, NADH+NAD+) levels, NAD+/NADH redox ratio, or both (Verdin, 2015; Lautrup et al., 2019; Katsyuba et al., 2020; McReynolds et al., 2020). In the first human study investigating the effect of aging on brain NAD, it was found that tNAD, NAD+, and NAD+/NADH redox ratio were indeed all decreased with age while NADH increased (Zhu et al., 2015). In psychotic disorders such as schizophrenia and bipolar disorders, an increase in NADH and a decrease in NAD+/NADH redox ratio was consistently observed in the frontal lobe of the brain vs. age-matched controls (Chouinard et al., 2017; Kim et al., 2017)

Bernard Cuenoud1*, Özlem Ipek2, Maya Shevlyakova3, Maurice Beaumont3, Stephen C. Cunnane4, Rolf Gruetter5 and Lijing Xin6*   Front. Aging Neurosci., 16 December 2020 | https://doi.org/10.3389/fnagi.2020.609517