Applying an Untargeted Metabolomic Strategy to Explore the Interventional Effect and Mechanism of NMN on Aging Model Mice

Abstract

Background: Aging is usually accompanied by a significant decline in nicotinamide adenine dinucleotide (NAD⁺) level. Nicotinamide mononucleotide (NMN) is a crucial precursor molecule of NAD⁺ with a variety of bioactivities beneficial to health, and the present study just aimed to explore the antiaging effects of NMN and the mechanism of action by using a nontargeted metabolomic strategy.

Methods: An aging mouse model induced by D-galactosamine (D-gal) was established, which was followed by treatment with NMN (at doses of 100 to 500 mg/kg per day) via oral administration for 10 weeks. The physiological and biochemical changes involved in the aging process were closely monitored to investigate the interventional effects of NMN. Plasma samples were subjected to assay by UPLC-Q-Orbitrap HRMS to reveal the mechanism of action via systematic data mining and statistical analysis.

Results: D-gal injection at a dose of 500 mg/kg per day for 7 weeks successfully induced the aging model in mice. Long-term supplementation with NMN could significantly improve the antioxidant and immune function, boost lipid metabolism, and reduce aging-related inflammatory response in a dose- and time-dependent manner. The nontargeted metabolomic analysis further demonstrated that the interventional effect of NMN on aging mice may be closely related to the regulation of lipid and purine metabolism.

Conclusions: Long-term NMN supplementation could display robust antiaging effects mainly by regulating lipid and purine metabolism, which thus deserves great attention for antiaging intervention.