在表达裸鼹鼠透明质酸合酶2转基因后表现出健康寿命改善、炎症衰老减少和寿命延长的小鼠中，年龄相关性听力损失持续存在。
Age-related hearing loss persisted in mice that had demonstrated improved healthspan, reduced inflammaging and extended lifespan following expression of the naked mole-rat transgene for hyaluronan synthase 2.
文献信息
| PMID | 42724209 |
|---|---|
| 原文 | 在 PubMed 查看原文 ↗ |
| 发表日期 | 2026 |
| 作者 | Connor E Owens |
| 作者单位 | Department of Population Medicine and Diagnostic Sciences, Cornell University, College of Veterinary Medicine, Ithaca, NY, United States. |
| 期刊 | Frontiers in aging |
| SCI 分区 | Q2 |
| IF | 5.2 |
| 研究类型 | 基础研究 · 基础／转化 |
| 所属专科 | 耳科 |
中文摘要
背景： 在65-74岁的成年人中，大约每三人就有一人报告听力困难，包括年龄相关性听力损失（AHL，老年性耳聋）。C57BL/6小鼠因其相对较早发生AHL而被广泛用于AHL的临床前研究。热量限制（CR）可减轻该品系的AHL并改善健康寿命和寿命。最近开发的一种表达裸鼹鼠透明质酸合酶2（nmrHas2）的转基因C57BL/6小鼠，可产生极高分子量透明质酸（vHMM-HA），也表现出健康寿命改善、炎症衰老减少和寿命延长。因此，我们评估了nmrHas2小鼠是否有AHL减轻的证据。
目的： 确定nmrHas2小鼠的AHL是否减轻。
方法： 本研究是一项关于nmrHas2与雌性生殖衰老的更大规模研究的补充。在1月龄时给予他莫昔芬，以在nmrHas2+雌鼠中诱导普遍存在的nmrHas2表达；nmrHas2-对照接受他莫昔芬或溶媒。在小鼠达到3或12月龄前约2周进行听性脑干反应（ABR）测试。约2周后安乐死并收集耳蜗和生殖组织。
结果： 对咔嗒声和六种纯音（4-32 kHz）的ABR阈值显示，在nmrHas2+小鼠和对照中，从3月龄到12月龄均出现明显听力损失，没有证据表明nmrHas2减轻了AHL。通过定量RT-PCR证实了nmrHas2+小鼠耳蜗中的nmrHas2表达。
结论： 尽管先前报道nmrHas2对其他衰老表型有益，但普遍存在的nmrHas2表达并未减轻C57BL/6小鼠的AHL。这些发现与CR形成对比，提示vHMM-HA和CR通过不同机制影响衰老。
英文摘要
BACKGROUND: Approximately one in three adults aged 65-74 years reports hearing difficulty, including age-related hearing loss (AHL, presbycusis). The C57BL/6 mouse is widely used in preclinical AHL research because it develops AHL relatively early. Calorie restriction (CR) attenuates AHL and improves healthspan and longevity in this strain. A recently developed transgenic C57BL/6 mouse expressing naked mole-rat hyaluronan synthase 2 (nmrHas2), which produces very high molecular mass hyaluronan (vHMM-HA), also exhibits improved healthspan, reduced inflammaging, and increased longevity. Therefore, we evaluated nmrHas2 mice for evidence of alleviated AHL.
OBJECTIVE: To determine whether AHL is attenuated in nmrHas2 mice.
METHODS: This study supplemented a larger investigation of nmrHas2 and female reproductive aging. Tamoxifen administered at 1 month induced ubiquitous nmrHas2 expression in nmrHas2+ females; nmrHas2- controls received tamoxifen or vehicle. Auditory brainstem response (ABR) testing was performed approximately 2 weeks before mice reached 3 or 12 months of age. Cochleae and reproductive tissues were collected following euthanasia approximately 2 weeks later.
RESULTS: ABR thresholds to clicks and six tones (4-32 kHz) showed marked hearing loss from 3 to 12 months of age in both nmrHas2+ mice and controls, with no evidence that nmrHas2 attenuated AHL. Cochlear nmrHas2 expression in nmrHas2+ mice was confirmed by quantitative RT-PCR.
CONCLUSION: Ubiquitous nmrHas2 expression did not attenuate AHL in C57BL/6 mice despite previously reported benefits for other aging phenotypes. These findings contrast with CR, suggesting that vHMM-HA and CR influence aging through distinct mechanisms.