Administration of nicotinamide mononucleotide suppresses the progression of age-related hearing loss in mice.

Age-related hearing loss (ARHL) is a widespread problem in the elderly, significantly impairing their quality of life. Despite its high prevalence, no fundamental treatment for ARHL has been established. Nicotinamide adenine dinucleotide (NAD) is required for various biological processes and tissue levels of the coenzyme NAD are known to decrease with age. A previous report suggested that declining NAD levels induce age-related diseases and NAD supplementation might be effective for treating or preventing age-related diseases. To clarify the effect of NAD supplementation on ARHL, C57BL/6J mice used as an animal model of ARHL were treated with nicotinamide mononucleotide (NMN), a precursor of NAD. Oral administration of NMN at 500 mg/kg/day effectively suppressed the development of ARHL in C57BL/6J mice. To elucidate the mechanism by which NMN administration suppressed the development of ARHL, NAD-related metabolites were assessed, and a comprehensive transcriptomic analysis of the inner ear tissue was performed. NMN administration resulted in increased NAD levels in inner ear tissues and induced changes in the transcriptome, specifically in genes related to metal ion metabolism. These findings suggest that NMN administration enhanced NAD levels in inner ear tissues, modulating metal ion metabolism to potentially protect against oxidative stress. This study provides a novel therapeutic approach to mitigating ARHL through NAD supplementation.