Treatment of presbycusis focused on cellular senescence

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K18286
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56050:Otorhinolaryngology-related
• Research Institution: Kyushu University
• Principal Investigator: TSUCHIHASHI NANA 九州大学, 医学研究院, 共同研究員 (20826333)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 細胞老化 / 老人性難聴 / セノリティック薬

Outline of Final Research Achievements

Since senescent cells may be involved in the pathogenesis of senile deafness, we measured hearing over time using ABR and detected senescent cells in the inner ear using senescence-accelerated mice (SAMP8) and their control mice (SAMR). Contrary to expectations, senescent cells were found to accumulate in spiral ganglion cells as early as 8 weeks of age, with significant expression in spiral ganglion cells even at 6 months of age and evident accumulation over time in hair cells or on stria vascularis. Senolytic drugs with activity to induce selective cell death in senescent cells were administered to SAMP8, but no clear improvement in hearing was obtained in this study. This suggests the need to reevaluate the effects of cellular senescence on hearing.

Free Research Field

耳科学

Academic Significance and Societal Importance of the Research Achievements

老人性難聴は1500万人を超す罹患者を持ち、聴力低下に加え社会的影響も甚大な疾患であるが、病態解明や根本的治療法の開発は進んでいない。一方、酸化ストレスなどで誘導される老化細胞の蓄積が加齢性疾患の発症に強く関与することが明らかとなってきた。本研究では老人性難聴における細胞老化の意義について検討した。当初老人性難聴の進行に老化細胞の経時的蓄積が関わると推測したが、実験の結果、老化細胞は若年マウスのらせん神経節細胞に発現著明であり、細胞老化がむしろストレスによる組織の変性を防ぎ、組織の修復を促進する方向に働くのではと考えられた。今後の研究で内耳の細胞老化の機能、聴覚に与える影響の解明が望まれる。