Long-Term Administration of Nicotinamide Mononucleotide Mitigates High-Fat-Diet-Induced Physiological Decline in Aging Mice.

Background: Nicotinamide adenine dinucleotide (NAD ⁺ ) levels decline with age, and boosting it can improve multi-organ functions and lifespan.
Objectives: Nicotinamide mononucleotide (NMN) is a natural NAD ⁺ precursor with the ability to enhance NAD ⁺ biosynthesis. Numerous studies have shown that a high-fat diet (HFD) can accelerate the process of aging and many diseases. We hypothesized that long-term administration of NMN could exert protective effects on adipose, muscle, and kidney tissues in mice on an HFD act by affecting the autophagic pathway.
Methods: Mice at 14 mo of age were fed an HFD, and NMN was added to their drinking water at a dose of 400 mg/kg for 7 mo. The locomotor ability of the mice was assessed by behavioral experiments such as grip test, wire hang test, rotarod, and beam-walking test. At the end of the behavioral experiments, the pathological changes of each peripheral organ and the expression of autophagy-related proteins, as well as the markers of the senescence and inflammaging were analyzed by pathological staining, immunohistochemical staining, and western blotting, respectively.
Results: We found that NMN supplementation increased NAD ⁺ levels and ultimately attenuated age- and diet-related physiological decline in mice. NMN inhibited HFD-induced obesity, promoted physical activity, improved glucose and lipid metabolism, improved skeletal muscle function and renal damage, as well as mitigated the senescence and inflammaging as demonstrated by p16, interleukin 1β, and tumor necrosis factor α levels. In addition, the present study further emphasizes the potential mechanisms underlying the bidirectional relationship between NAD ⁺ and autophagy. We detected changes in autophagy levels in various tissue organs, and NMN may play a protective role by inhibiting excessive autophagy induced by HFD.
Conclusions: Our findings demonstrated that NMN administration attenuated HFD-induced metabolic disorders and physiological decline in aging mice.
Competing Interests: Conflict of interest The authors report no conflicts of interest.
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