Transcript from mice inner ear tissue

Age-related hearing loss (ARHL) is a common 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 NAD+ levels are known to decrease with aging. Previous report suggested that declining NAD+ levels induce age-related diseases and NAD+ supplementation might be effective for preventing and treating 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+. As a result, we founded that orally 500 mg/kg/day NMN administration effectively suppresses the development of ARHL in C57BL/6J mice. For revealing the mechanism of suppresses the development of ARHL by NMN administration, NAD+-related metabolite and comprehensive transcriptomic analysis in inner ear tissue were 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 enhances NAD+ levels in inner ear tissues, modulating metal ion metabolism and potentially protecting against oxidative stress. This study provides a novel therapeutic approach for ARHL through NAD+ supplementation.