European Journal of Pharmaceutical Sciences · Oct 28, 2026

Alginate Oligosaccharide Alleviates Age-Related Hearing Loss via TFEB-Associated Autophagy Restoration to Attenuate Oxidative Stress and Inflammation

By Su S, Zhang X, Li M et al.

Age-related hearing loss (ARHL) is a highly prevalent sensory disorder characterized by progressive cochlear degeneration. To date, no effective pharmacological treatment is clinically available. In this study, we investigated the otoprotective efficacy and underlying mechanisms of alginate oligosaccharide (AOS) against D-galactose (D-gal)-induced senescence in vitro and age-associated cochlear dysfunction in C57BL/6J mice. Multi-omics analyses identified oxidative stress, inflammation, cellular senescence, and autophagy, as core targeted pathways associated with AOS treatment. In D-gal-treated HEI-OC1 cells and cochlear explants, AOS treatment markedly reduced senescence-associated β-galactosidase (SA-β-gal) activity and downregulated senescence markers P16 and P21. These anti-senescent effects were accompanied by ameliorated oxidative and pro-inflammatory stress, as reflected by decreased reactive oxygen species (ROS), preserved mitochondrial function, and suppressed nuclear factor-κB/NOD-like receptor pyrin domain-containing 3 (NF-κB/NLRP3) signaling. AOS also promoted transcription factor EB (TFEB) nuclear translocation and attenuated D-gal-induced autophagy-related dysregulation. Pharmacological inhibition of autophagy and TFEB nuclear entry effectively blunted these cytoprotective, antioxidant, and anti-inflammatory benefits of AOS, supporting the involvement of TFEB-associated autophagic signaling in AOS-mediated protection. In C57BL/6J mice, long-term AOS administration significantly lowered auditory brainstem response (ABR) thresholds, attenuated the age-related degeneration of hair cells and spiral ganglion neurons, and reduced cochlear senescence markers. Furthermore, AOS suppressed MDA accumulation, elevated SOD activity, inhibited NF-κB/NLRP3 activation, and restored TFEB-associated autophagic homeostasis in vivo. Collectively, these findings suggest that AOS protects against age-associated cochlear dysfunction and senescence, accompanied by reduced oxidative stress and inflammation and improved autophagy-related homeostasis. TFEB-associated signaling may contribute to these protective effects, supporting further investigation of AOS for the prevention or delay of cochlear aging.

doi.org/10.1016/j.ejps.2026.107703Open accessPubMed 42951215Interventions