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

Abstract

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.