Activity of proteins, sirtuins, regulating metabolic health declines with age. Scientists have previously sought methods to increase sirtuin activity as people age including proposing the use of nutraceuticals, such as NMN, to improve symptoms of age-associated diseases.1,2 The role of other mechanisms through which NMN supplementation may confer improvements of age-related diseases have received less attention.
Data indicate NMN supplementation improves nicotinamide adenine dinucleotide (NAD+) levels in cells through aging. NAD+ levels play critical roles in pathways of metabolism, including the production of energy molecules, ATP. The authors investigate whether raising NAD+ cellular levels with NMN supplementation may affect cellular pathways in metabolism to confer cardioprotection benefits in age-related diseases.
Image from Nadtochiy et al. (2018)
The research team finds NMN protects blood vessels from ischemia, regardless of sirtuin activity. The scientists treat mice with splitomicin, a sirtuins inhibitor. Previous research using splitomicin indicates this drug blocks cardioprotection coming from high levels of sirtuins.2,3 Even with splitomicin treatment, NMN still confers cardioprotective effects.
Image from Nadtochiy et al. (2018) indicating NMN stimulates higher levels of molecules associated with glycolysis (glycolytic intermediates)
The scientists’ data show NMN stimulates a key reaction of metabolism–glycolysis. The delivery of NMN to the mouse heart results in a significant elevation in NAD+. The scientists run analyses to measure levels of molecules in cells known to be associated with glycolysis and find that NMN deliverysignificantly elevated levels of molecules associated with glycolysis. These data indicate NMN stimulates glycolysis and energy production in the form of ATP through increasing NAD+ levels in cells.
Image from Nadtochiy et al. (2018)
In order to demonstrate glycolysis is required for NMN cardioprotection , the team blocks glucose in the hearts of mice treated with NMN. The scientists thus demonstrate blocking glucose also blocks the protective benefits from NMN.
“Together with our data showing NMN stimulates glycolysis, these findings suggest that NMN-induced cardioprotection may proceed in part via enhancement of glycolysis,”2 says the scientists of the study. It appears enhanced glycolysis confers protection through improving bioenergetics.2 This study suggests NMN supplementation may confer benefits in disease states, such as ischemia, through more than one molecular pathway. For instance, NMN may confer physiological benefits in age-related diseases through stimulation of sirtuins; however, stimulation of production of energy molecules through glycolysis could be another means through which these benefits arise.
Sergiy M. Nadtochiy, Yves T. Wang, Keith Nehrke, Josh Munger, Paul S. Brookes. Cardioprotection by nicotinamide mononucleotide (NMN): Involvement of glycolysis and acidic pH. J Mol Cell Cardiol, 2018; DOI: 10.1016/j.yjmcc.2018.06.007.
- Shin-ichiro Imai, Leonard Guarente. NAD+ and sirtuins in aging and disease. Trends Cell Biol, 2014; DOI: 10.1016/j.tcb.2014.04.002.
- Sergiy M. Nadtochiy, Yves T. Wang, Keith Nehrke, Josh Munger, Paul S. Brookes. Cardioprotection by nicotinamide mononucleotide (NMN): Involvement of glycolysis and acidic pH. J Mol Cell Cardiol, 2018; DOI: 10.1016/j.yjmcc.2018.06.007.
- Sergiy M. Nadtochiy, Hongwei Yao, Michael W. McBurney, Wei Gu, Leonard Guarente, Irfan Rahman, Paul S. Brookes. SIRT1-mediated acute cardioprotection. Am J Physiol Heart Circ Physiol, 2011; DOI: 10.1152/ajpheart.00587.2011.