NMN Improves Mitochondrial Health in Multiple Ways

NMN is the precursor of NAD+. A large number of studies have confirmed that NMN fights aging by increasing the level of NAD+, so the mitochondrial dysfunction caused by aging is no exception.

Recently, scientists from Kyushu University in Japan gave a new perspective. They found that NMN can improve mitochondrial health through two independent metabolic pathways rather than relying on NAD+ . This means that NMN may have a better effect on improving mitochondrial health than other NAD+ precursors.

To explore the specific effect of NMN on mitochondrial metabolism, the researchers first treated HEK293 kidney cells with 2.5 mM NMN for 3 days, and then measured mitochondrial metabolites. The results showed that pathways related to amino acid, nucleotide and niacin metabolism were activated both in cells and in mitochondria.

Nucleotide synthesis pathways include de novo synthesis and salvage synthesis, and de novo synthesis is usually used in HEK293 kidney cells. In order to determine which type of nucleotide synthesis is activated by NMN, the researchers treated kidney cells with mtDNA inhibitors ddC and ddI. The results showed that after NMN supplementation, the ratio of pyrimidine nucleotides was higher than that of purine nucleotides. This suggests that NMN can activate the de novo synthesis of pyrimidine nucleotides.

After 3 days of NMN treatment, only the level of ubiquinone in the cells increased significantly. To determine the reason for the increase in ubiquinone levels, the researchers labeled ubiquinone precursors with stable isotopes, and the results showed that the isotope-labeled ubiquinone levels increased over time after NMN treatment, indicating that NMN can activate ubiquinone synthesis.

Experiments demonstrated that high levels of ubiquinone increased nucleotide synthesis under conditions of increased demand for mtDNA replication, implying that additional pathways exist to activate nucleotide synthesis.

Tag: NMN

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