Scholarlink

Objective <p>Age-related hearing loss (ARHL) is largely attributed to dysfunction of the cochlear stria vascularis (SV). This study aimed to define the molecular mechanisms underlying SV aging and identify therapeutic targets.</p> Methods <p>Lifespan transcriptomic profiling and systems-level analyses were performed on mouse cochleae to reveal age-associated pathways. Functional and pharmacological assays were used to examine the effects of IκB kinase (IKK) inhibition both in vitro and in aging mice.</p> Results <p>Aged SV displayed profound transcriptional reprogramming toward a pro-inflammatory and metabolically impaired state. A regulatory hub comprising AP-1, NF-κB, and CEBPB was identified as a master inflammatory switch. TNFα activation disrupted the blood-labyrinth barrier and mitochondrial function, while IKK inhibition reversed these effects and mitigated hearing loss in aging mice.</p> Conclusions <p>Targeting the IKK–NF-κB axis preserves cochlear integrity and offers a promising therapeutic strategy to prevent age-related hearing loss.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Targeting a master inflammatory switch in the aging cochlea attenuates sensory decline

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年2月2日

查看全文
  • Ying-Xian He,
  • Huan-Guang Cao,
  • Kun-Ping Huang

摘要

Objective

Age-related hearing loss (ARHL) is largely attributed to dysfunction of the cochlear stria vascularis (SV). This study aimed to define the molecular mechanisms underlying SV aging and identify therapeutic targets.

Methods

Lifespan transcriptomic profiling and systems-level analyses were performed on mouse cochleae to reveal age-associated pathways. Functional and pharmacological assays were used to examine the effects of IκB kinase (IKK) inhibition both in vitro and in aging mice.

Results

Aged SV displayed profound transcriptional reprogramming toward a pro-inflammatory and metabolically impaired state. A regulatory hub comprising AP-1, NF-κB, and CEBPB was identified as a master inflammatory switch. TNFα activation disrupted the blood-labyrinth barrier and mitochondrial function, while IKK inhibition reversed these effects and mitigated hearing loss in aging mice.

Conclusions

Targeting the IKK–NF-κB axis preserves cochlear integrity and offers a promising therapeutic strategy to prevent age-related hearing loss.