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Updated: Mar 1, 2026
Cochlear Surface Preparation in the Adult Mouse
Published on: November 6, 2019
NRH attenuates age-related hearing loss by suppressing cochlear ferroptosis and cellular senescence via Sirt3
Chenyang Yuan1, Chen Feng2, Tianyu Ma3
1Department of Otolaryngology Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China; Department of Otorhinolaryngology Head and Neck Surgery, The First Hospital Affiliated to Harbin Medical University, Harbin, Heilongjiang, China; Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Otolaryngology Institute of Shanghai Jiao Tong University, Shanghai Key Laboratory of Sleep Disordered Breathing, 600 Yishan Rd, Shanghai, China.
Background:
Age-related hearing loss (ARHL) is a prevalent sensory disorder with significant clinical and social burdens, yet no FDA-approved pharmacological treatments are currently available. Emerging evidence implicates declined cellular NAD+ levels in the pathogenesis of age-related diseases, suggesting NAD+ metabolism as a potential therapeutic target.
Purpose:
In this study, we investigate the efficacy of Dihydronicotinamide riboside (NRH), a highly bioavailable NAD+ precursor, in mitigating ARHL.
Methods:
C57BL/6 mice were used as animal model of ARHL and received oral administration of NRH (125 mg/kg) every other day. Then hearing thresholds were assessed and cochlear structure was evaluated. D-galactose (D-gal)-induced aging models were generated using organ explants and HEI-OC1 cells to investigate the protective effects of NRH treatment. Transcriptomic profiling and molecular docking characterized NRH's mechanism of action, while H&E staining confirmed its safety profile. Temporal NRH metabolism in organ explants was tracked using fluorophore-conjugated NRH.
Results:
NRH administration ameliorated ARHL in C57BL/6 mice, as evidenced by improved auditory thresholds and elevated cochlear NAD+ levels. Treatment preserved cochlear hair cells, synapses, and auditory neurons. Mechanistically, NRH activated Sirt3, thereby inhibiting oxidative stress and lipid peroxidation via modulation of ferroptosis-related pathways, ultimately mitigating cochlear cellular senescence. NRH demonstrated a favorable safety profile and exhibited temporal distribution across distinct cochlear cell types.
Conclusion:
Our findings demonstrate that NRH mitigates ARHL in C57BL/6 mice, holding significant translational potential for ARHL treatment.
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