Preclinical animal and cellular study

Nicotinamide Mononucleotide Improves High-Fat Diet-Induced Myocardial Damage of Aging Mice through the Sirt3/PINK1/Parkin Signaling Pathway

Xin Wen et al. · The Journal of Nutrition · 2026

Evidence type: Preclinical mechanistic study Interpretive weight: Mechanistic contextResearch area: Cardiac aging and mitochondrial autophagy
DesignPreclinical long-term high-fat-diet aging-mouse study plus palmitic-acid cardiomyocyte experiments and pathway inhibition
Population14-month-old male C57BL/6J mice and H9c2 cardiomyocytes
SampleNormal-diet, HFD and HFD-plus-NMN animal groups; see publication
InterventionNMN 400 mg/kg in drinking water for 7 months in HFD-fed aging mice; NMN in palmitic-acid cell model
EndpointsMyocardial histology and fibrosis; Senescence and inflammatory markers; Apoptosis; Sirt3, PINK1 and Parkin; Autophagy-lysosomal markers; Cardiomyocyte viability and autophagy flux

What the publication reported

This 2026 study examined whether long-term NMN altered cardiac injury in aging mice fed a high-fat diet and explored mitochondrial-autophagy mechanisms in cardiomyocytes.

NMN reduced fibrosis and multiple inflammatory, senescence and apoptotic markers in the mouse hearts and increased Sirt3, PINK1, Parkin and autophagy-related signals. In cell experiments, blocking Sirt3 abolished several NMN-associated effects.

The findings support a mechanistic Sirt3/PINK1/Parkin hypothesis in a high-fat-diet mouse model. They do not establish that NMN prevents or treats cardiomyopathy or heart disease in humans.

Key findings

  • NMN reduced myocardial fibrosis and several senescence/inflammatory markers in HFD-fed aging mice.
  • Apoptosis-related markers were reduced.
  • Sirt3, PINK1, Parkin and autophagy-lysosomal markers increased.
  • Sirt3 inhibition blocked key protective effects in cardiomyocyte experiments.
  • The entire efficacy evidence was preclinical.

What it cannot establish

  • Mouse disease model and cultured cardiomyocytes only.
  • 400 mg/kg long-term mouse dosing cannot be directly translated to humans.
  • High-fat-diet metabolic cardiomyopathy is a specific experimental model.
  • No human cardiovascular outcomes were studied.
HealthspanX claim boundary: This study does not establish that NMN prevents or treats cardiomyopathy, heart failure or other cardiovascular disease in humans.

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