Preclinical animal study

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

Ao-Jia Zhou et al. · The Journal of Nutrition · 2025

Evidence type: Preclinical mechanistic study Interpretive weight: Mechanistic contextResearch area: Diet-accelerated aging and metabolism
DesignLong-term preclinical intervention study in aging mice fed a high-fat diet
Population14-month-old mice fed a high-fat diet
SampleMultiple normal-diet, HFD and HFD-plus-NMN groups; see publication
InterventionNMN 400 mg/kg in drinking water for 7 months with high-fat diet
EndpointsNAD+; Body weight and metabolic measures; Physical activity and motor tests; Skeletal muscle function; Renal pathology; Inflammation and senescence markers; Autophagy-related proteins

What the publication reported

This long-duration study tested NMN in aging mice exposed to a high-fat diet for seven months.

NMN increased NAD+ and was associated with less obesity, better glucose and lipid measures, improved activity and muscle tests, less renal damage, and changes in inflammatory, senescence and autophagy markers.

The high-fat-diet mouse model is useful for mechanistic work but cannot establish that NMN treats obesity, metabolic disease or aging in humans.

Key findings

  • NMN increased NAD+ in the model.
  • High-fat-diet-associated weight and metabolic phenotypes were attenuated.
  • Physical-activity and skeletal-muscle measures improved.
  • Renal pathology, inflammation and senescence-related markers were reduced.
  • Autophagy-related pathways were altered across tissues.

What it cannot establish

  • Mouse high-fat-diet model only.
  • High experimental dose and seven-month mouse exposure are not directly translatable to humans.
  • Many endpoints were measured across multiple organs.
  • No human obesity, kidney or aging outcomes were assessed.
HealthspanX claim boundary: This study does not establish that NMN treats obesity, metabolic disease, kidney disease or aging in humans.

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