NMN Studies

To evaluate the anti-aging action of NMN in vitro, scientists assessed the effects of NMN on cellular mtROS production and mitochondrial phenotype in cultured primary cerebromicrovascular endothelial cells (CMVECs). NMN attenuates mitochondrial oxidative stress and improves mitochondrial bioenergetics in aged cerebromicrovascular endothelial cells. NMN treatment restores NO release in aged CMVECs in vitro and that NMN supplementation also rescues endothelial NO-mediated vasodilation in the aortas of aged mice^[1].

Nicotinamide mononucleotide adenylyltransferase (NMNAT) is the central enzyme of the NAD biosynthetic pathway. The conversion of NMN to NAD+ is catalyzed by three enzyme isoforms—namely, NMN adenyltransferases (NMNATs) that are differentially localized (NMNAT1, nucleus; NMNAT2, Golgi, cytosol-facing; NMNAT3, mitochondria)^[2].

When NMN was added to the culture medium for 1 h, its intracellular contents increased in both cell types (HeLa and U937 cells), indicating that the nucleotide readily permeates the plasma membrane. Accordingly, NAD contents increased in both HeLa and U937 cells exposed to NMN. NMN reduces NAD and ATP depletion in cells undergoing PARP-1 hyperactivation, significantly delaying cell death^[3].

In human cells, NMN is available as a source of cellular energy. Mitochondria are intracellular powerhouses that produce ATP and carry out diverse functions for cellular energy metabolism. Mitochondrial ATP production and membrane potential require the universal cofactor nicotinamide adenine dinucleotide(NAD)^[4]. NMN increases cellular energy by converting to NAD in cells.

Obesity is associated with adipose tissue dysfunction and multi-organ insulin resistance. Administrating NMN improved multi-organ insulin sensitivity, increased adiponectin production, and decreased free fatty acids production^[5]. Feeding mice with drinking water containing NMN inhibited age-induced weight gain^[6]. NAD+ and NAMPT levels decrease in multiple organs during aging, and NMN improves glucose intolerance and lipid profiles in age-induced Type 2 Diabetes mice. NMN is a potential nutriceutical intervention against diet- and age-induced Type 2 Diabetes^[11].

Amyloid-β (Aβ) oligomers are recognized as the primary neurotoxic agents in Alzheimer’s disease (AD). Impaired brain energy metabolism and oxidative stress are implicated in cognitive decline in AD. NMN restored levels of NAD+ and ATP, eliminated the accumulation of reactive oxygen species (ROS) in the Aβ oligomer-treated hippocampal slices. The present study indicates that NMN could restore cognition in AD model rats. The beneficial effect of NMN is produced by ameliorating neuron survival, improving energy metabolism and reducing ROS accumulation^[7].

Photoreceptor death is the endpoint of many blinding diseases. Rod or cone photoreceptor-specific deletion of nicotinamide phosphoribosyltransferase (Nampt), the rate-limiting enzyme in the major NAD+ biosynthetic pathway beginning with nicotinamide, causes retinal degeneration. In both cases, we could rescue vision with nicotinamide mononucleotide (NMN)^[8].

Research has shown that NMN helps protect from ischemia^[9], a result of insufficient blood flow in any area of the body. Typically, the body defends itself from ischemia via ischemic preconditioning (IPC)^[10]. IPC stimulates SIRT1, which is an NAD+ dependent sirtuin^[9], which helps move blood throughout the body. Because NMN activates SIRT1, then, it has the ability to mimic IPC, and thus is capable of protecting the heart from ischemia and reperfusion^[9]!