在circHERC1-A端粒酶激活剂中.
Yumeng Cui1, Yingying He1, Xiaojie Wu1
1Laboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, Beijing 100071, China.
Science advances
|November 12, 2025
概括
循环RNA HERC1 (circHERC1) 在衰老细胞中重新激活端粒酶逆转录酶 (TERT). 恢复circHERC1可以改善端粒长度,逆转衰老迹象,增强功能,提供一种新的抗衰老治疗点.
科学领域:
- 分子生物学分子生物学
- 衰老研究研究 衰老研究
- 基因组学就是基因组学.
背景情况:
- 端粒维护和基因组稳定性至关重要,端粒酶活性在老化的体细胞中通常会下降.
- 端粒酶逆转录酶 (TERT) 是端粒酶的催化子单元,对于端粒维护至关重要.
研究的目的:
- 研究circHERC1在调节端粒酶活性中的作用及其作为抗衰老干预的潜力.
- 阐明circHERC1影响TERT转录的机制.
主要方法:
- 鉴定circHERC1作为TERT转录调节剂.
- 对circHERC1与TERT促进体结合的分析以及RNA聚合酶II和c-Fos.的招募.
- 评估cirHERC1表达的变化随着年龄的增长.
- 在老年模型中实验恢复cirHERC1水平.
- 在体内通过腺相关病毒载体和细胞外囊泡传递circHERC1.
主要成果:
- circHERC1直接结合TERT促进体,通过招募关键的转录机械来促进TERT的表达.
- 循环HERC1水平随着年龄的增长而下降,与减少的端粒酶活性相关.
- 恢复 circHERC1 增强端粒酶活性,延长端粒,并逆转衰老的表型.
- circHERC1的输送减轻了衰老,改善了认知和身体功能,并减少了老年模型的炎症.
结论:
- circHERC1是一种新型的端粒酶活性调节剂,是衰老过程中的关键因素.
- circHERC1的恢复代表了一种有前途的治疗策略,用于对抗与年龄相关的衰退和促进长寿.
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