Unveiling the Modulation of NMN Supplementation on Mitochondrial Homeostasis

Mitochondria, a type of highly plastic organelle, can maintain a relatively stable dynamic equilibrium state towards the morphology, structure, quantity, volume, quality, and function under normal physiological conditions. This dynamic equilibrium state is generally called mitochondria homeostasis. Replenishment of nicotinamide mononucleotide (NMN) to boost intracellular NAD⁺ level can regulate mitochondrial homeostasis.

Typically, NAD⁺ level determines the rate and extent of senescence. The NAD⁺ pool experienced by cells and tissues presents a declined tendency with age, which may lead to a loss of mitochondrial homeostasis and senescent phenotypes in CD8⁺ T cells. 

Following NMN (100 μM) supplementation, NAD⁺ level is restored and the NAD⁺/NADH ratio is elevated in senescent CD8⁺ T cells, by which the mitochondrial functions are obviously improved and the cytoplasmic mtDNA is reduced.

Post NMN supplementation, the senescence and neuroinflammation are correspondingly repressed. With a great detail, NMN supplementation decreases the ROS and mitochondrial membrane potential in CD8⁺ T cells, while increasing the intracellular ATP. Furthermore, NMN suppresses the inflammation-associated markers (IL-1β, IL-6, TNF-α and IFN-γ) in the supernatant and the mRNA of senescent CD8⁺ T cells. 

The activation of STING can launch a robust proinflammatory response and senescence, which is closely related to the deficient health span in model mice. Strikingly, NMN can prominently improve the senescent state of T cells and reduce the secretion of senescence-related inflammatory factors via inhibition of the STING pathway.

Upregulation of NAD+ level by NMN supplementation can regulate the mitochondrial homeostasis to prevent STING-induced senescence in CD8⁺ T cells.

Ye B, Pei Y, Wang L, et al. NAD⁺ supplementation prevents STING-induced senescence in CD8⁺ T cells by improving mitochondrial homeostasis. J Cell Biochem. 2024;1-17. doi:10.1002/jcb.30522

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