Academician Workstation of Hainan University (School of Pharmaceutical Sciences), Yazhou Bay, Sanya, Hainan 572000, China; Artificial Auditory Laboratory of Jiangsu Province, Xuzhou Medical University, Xuzhou, Jiangsu 221000, China.
Artificial Auditory Laboratory of Jiangsu Province, Xuzhou Medical University, Xuzhou, Jiangsu 221000, China; Beijing Friendship Hospital, Capital Medical University, Beijing 100000, China.
Mech Ageing Dev. 2024 Oct;221:111964. doi: 10.1016/j.mad.2024.111964. Epub 2024 Jul 15.
Age-related hearing loss (ARHL) is an auditory disease characterized by gradual loss of high-frequency hearing sensitivity. Excessive reactive oxygen species trigger NLRP3-inflammasome activation that may be crucial for ARHL pathogenesis. The antioxidant factor Sestrin2 (SESN2) has been reported to be involved in the remission of oxidative stress and ARHL. However, the mechanism by which SESN2 protects auditory cells in the aging mouse cochlea remains unknown. Here, we observed that ectopic overexpression of SESN2 delayed ARHL, whereas SESN2 knockdown accelerated it. Importantly, we elucidated that SESN2 exerts a hearing-protective effect by inhibiting the production of NLRP3 by acting as a mitophagy agonist. Our study proposes a new theoretical basis for SESN2 prevention of ARHL and provides a novel therapeutic strategy for maintaining SESN2 activity in the aging cochlea.
年龄相关性听力损失（ARHL）是一种听觉疾病，其特征是高频听力敏感度逐渐丧失。过量的活性氧触发 NLRP3-炎症小体激活，这可能对 ARHL 的发病机制至关重要。抗氧化因子 Sestrin2（SESN2）已被报道参与氧化应激和 ARHL 的缓解。然而，SESN2 保护衰老小鼠耳蜗听觉细胞的机制尚不清楚。在这里，我们观察到 SESN2 的异位过表达延迟了 ARHL，而 SESN2 的敲低则加速了它。重要的是，我们阐明了 SESN2 通过作为自噬激动剂来抑制 NLRP3 的产生发挥听力保护作用。我们的研究为 SESN2 预防 ARHL 提供了一个新的理论基础，并为维持衰老耳蜗中 SESN2 的活性提供了一种新的治疗策略。
