Senolytic treatment alleviates cochlear senescence and delays age-related hearing loss in C57BL/6J mice

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2025-04-15 DOI:10.1016/j.phymed.2025.156772

Yi Chen , Hongming Huang , Yuelian Luo , Haoyang Wu , Wenting Deng , Xin Min , Huilin Lao , Hao Xiong

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引用次数: 0

Abstract

Background

Age-related hearing loss (ARHL) is a prevalent sensory deficit that significantly affects quality of life in older individuals. Cellular senescence contributes to various age-related degenerative disorders. However, its effect on ARHL remains unclear.

Purpose

The aim of this study was to explore the therapeutic potential of senolytics in attenuating cochlear senescence and delaying the progression of ARHL.

Methods

The senolytic drugs dasatinib and quercetin (D + Q) were used to target senescent cells at different stages of ARHL in C57BL/6J mice. The impact of D + Q treatment on ARHL progression and cochlear degeneration was also assessed. Additionally, the protective effects of D + Q treatment were evaluated in HEI-OC1 auditory cells and cochlear explants. Transcriptomic analysis was conducted on cochlear explants subjected to different treatments.

Results

D + Q treatment at an early stage of ARHL significantly delayed ARHL progression and alleviated cochlear degeneration in male and female C57BL/6J mice. Treatment of mice with normal hearing also mitigated age-related hair cell loss. In HEI-OC1 auditory cells, D + Q treatment exerted protective effects by alleviating the senescence-associated secretory phenotype (SASP). Transcriptomic analysis of cochlear explants revealed that downregulation of inflammatory cytokines and chemokines was involved in the beneficial effects of D + Q treatment against cellular senescence. Mechanistically, D + Q treatment alleviated hair cell senescence via binding to NF-κB and inhibiting its activity.

Conclusion

Senolytics may offer a novel therapeutic strategy for attenuating cochlear senescence and slowing the progression of ARHL.

Abstract Image

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抗衰老治疗可减轻C57BL/6J小鼠耳蜗衰老并延缓年龄相关性听力损失

背景：年龄相关性听力损失（ARHL）是一种普遍存在的感觉缺陷，严重影响老年人的生活质量。细胞衰老有助于各种年龄相关的退行性疾病。然而，其对ARHL的影响尚不清楚。目的探讨抗衰老药在减缓耳蜗衰老和延缓ARHL进展方面的治疗潜力。方法采用抗衰老药物达沙替尼和槲皮素（D + Q）靶向C57BL/6J小鼠ARHL不同阶段的衰老细胞。还评估了D + Q治疗对ARHL进展和耳蜗变性的影响。此外，我们还评估了D + Q处理对HEI-OC1听觉细胞和耳蜗外植体的保护作用。对不同处理的耳蜗外植体进行转录组学分析。结果在ARHL早期给予d + Q治疗可显著延缓ARHL进展，减轻雌雄C57BL/6J小鼠耳蜗变性。对听力正常的小鼠进行治疗也能减轻与年龄相关的毛细胞损失。在HEI-OC1听觉细胞中，D + Q处理通过减轻衰老相关分泌表型（SASP）发挥保护作用。耳蜗外植体的转录组学分析显示，D + Q处理对细胞衰老的有益作用涉及炎症细胞因子和趋化因子的下调。机制上，D + Q处理通过结合NF-κB并抑制其活性来缓解毛细胞衰老。结论抗衰老药物可为减缓耳蜗衰老、减缓ARHL进展提供一种新的治疗策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Phytomedicine 医学-药学

CiteScore

10.30

自引率

5.10%

发文量

670

审稿时长

91 days

期刊介绍： Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.