Liting Zheng , Menghua Li , Yalan Li , Liyuan Wu , Konduru Naveena , Mengzhu Zheng , Zhanqun Yang , Yong Pan , Yunshi Zhang , Shujin Chen , Yuehua Qiao , Yice Xu , Long Chen , Xi Shi
{"title":"Sestrin2 通过抑制 NLRP3-炎症小体的活性，在老年性听力损失中发挥保护作用。","authors":"Liting Zheng , Menghua Li , Yalan Li , Liyuan Wu , Konduru Naveena , Mengzhu Zheng , Zhanqun Yang , Yong Pan , Yunshi Zhang , Shujin Chen , Yuehua Qiao , Yice Xu , Long Chen , Xi Shi","doi":"10.1016/j.mad.2024.111964","DOIUrl":null,"url":null,"abstract":"<div><p>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.</p></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"221 ","pages":"Article 111964"},"PeriodicalIF":5.3000,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Sestrin2 plays a protective role in age-related hearing loss by inhibiting NLRP3-inflammasome activity\",\"authors\":\"Liting Zheng , Menghua Li , Yalan Li , Liyuan Wu , Konduru Naveena , Mengzhu Zheng , Zhanqun Yang , Yong Pan , Yunshi Zhang , Shujin Chen , Yuehua Qiao , Yice Xu , Long Chen , Xi Shi\",\"doi\":\"10.1016/j.mad.2024.111964\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>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.</p></div>\",\"PeriodicalId\":18340,\"journal\":{\"name\":\"Mechanisms of Ageing and Development\",\"volume\":\"221 \",\"pages\":\"Article 111964\"},\"PeriodicalIF\":5.3000,\"publicationDate\":\"2024-07-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Mechanisms of Ageing and Development\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0047637424000642\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Mechanisms of Ageing and Development","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0047637424000642","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
Sestrin2 plays a protective role in age-related hearing loss by inhibiting NLRP3-inflammasome activity
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.
期刊介绍：
Mechanisms of Ageing and Development is a multidisciplinary journal aimed at revealing the molecular, biochemical and biological mechanisms that underlie the processes of aging and development in various species as well as of age-associated diseases. Emphasis is placed on investigations that delineate the contribution of macromolecular damage and cytotoxicity, genetic programs, epigenetics and genetic instability, mitochondrial function, alterations of metabolism and innovative anti-aging approaches. For all of the mentioned studies it is necessary to address the underlying mechanisms.
Mechanisms of Ageing and Development publishes original research, review and mini-review articles. The journal also publishes Special Issues that focus on emerging research areas. Special issues may include all types of articles following peered review. Proposals should be sent directly to the Editor-in-Chief.
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