Background <p>Mitochondrial dysfunction is considered one of the molecular mechanisms underlying age-related hearing loss (ARHL). While some studies have suggested that surtuin 1 (SIRT1) may improve mitochondrial function, delaying the onset of ARHL; other research has indicated that SIRT1 can exacerbate hair cell damage, leading to further hearing loss. We aimed to investigate the role of SIRT1 in ARHL and its associated molecular mechanisms.</p> Methods <p>Eight-week-old male C57BL/6J mice were randomly divided into three groups: control, D-galactose (D-gal), and D-gal+SIRT1. Auditory brainstem response (ABR) was tested to evaluate hearing function. Immunofluorescence (IF) staining was used to assess the number of ribbon synapses. The enzymatic chemistry was applied for measuring reactive oxygen species (ROS) production, and mitochondrial DNA (mtDNA) damage was assessed with RT-PCR. Additionally, western blot (WB) was used to detect SIRT1 protein levels.</p> Results <p>Compared with the control group, the D-gal group exhibited elevated ABR thresholds and decreased ABR I wave amplitude, as well as prolonged latency. The results also revealed a decrease in the number of ribbon synapses and increased ROS levels in the D-gal group, as well as decreased SIRT1 protein. SIRT1 overexpression mitigated hearing loss in D-gal-induced accelerated aging mice, with increased ABR I wave amplitude and shorter latency. WB analysis revealed that SIRT1 overexpression reduced total protein acetylation levels. Furthermore, SIRT1 overexpression decreased ROS production, mitigated mtDNA damage and significantly increased the number of synapses.</p> Conclusions <p>These findings demonstrate that SIRT1 overexpression suppresses oxidative stress in ARHL, thereby mitigating damage to inner hair cell ribbons and delaying the hearing deterioration in ARHL.</p>