Long-term NMN treatment increases lifespan and healthspan in mice in a sex dependent manner

Long-term NMN treatment increased median lifespan by 8.5% in female mice, with varying effects on healthspan and metabolic health in males.

Summary and findings

This study measured the effects of long-term nicotinamide mononucleotide (NMN) treatment on lifespan and healthspan in male and female mice. NMN increased median lifespan by 8.5% in females and reduced frailty in both sexes. The study also noted sex-specific effects on metabolic health and physical activity.

Abstract

<title>Abstract</title> <p>Nicotinamide adenine dinucleotide (NAD+) is essential for many enzymatic reactions. During aging, levels of NAD+ decrease by up to 50%, the repletion of which provides a range of health benefits in both mice and humans. It remains unknown, however, whether the NAD+ precursor nicotinamide mononucleotide (NMN) extends lifespan in mammals. Here, we investigate the effect of long-term NMN on the healthspan and lifespan of male and female mice. In both sexes, NMN reduced frailty, an effect that was associated with increased abundance of Anaerotruncus colihominis, a butyrate-producing gut bacterium. In females, but not males, NMN increased median lifespan by 8.5%, and upregulated mitochondrial function markers in metabolic tissues. In males, but not females, NMN increased physical activity and boosted metabolic health, whilst also upregulating inflammatory pathways, likely as a result of sex-specific increased expression of NAD+ consumers including CD38. These results highlight the potential of NAD+ boosters for treating age-related conditions.</p>

Key findings

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Limitations

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Elsewhere in the NAD+ (Nicotinamide Adenine Dinucleotide) corpus