在衰老过程中内源性逆转录病毒的复苏增强了衰老
Xiaoqian Liu1, Zunpeng Liu2, Zeming Wu3
1State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Institute for Stem cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Cell
|January 7, 2023
概括
古老的病毒元素叫做内源逆转录病毒 (ERVs) 在衰老过程中唤醒,驱动细胞衰老和组织退化. 抑制这些ERV可以缓解衰老标志物.
科学领域:
- 基因组学
- 老龄化研究
- 病毒学
背景情况:
- 内生逆转录病毒 (ERV) 是基因组中的休眠病毒元素.
- 在老化过程中ERV的作用仍然很少被研究.
- 最近的ERV,如人类内源性逆转录病毒K (HERVK/HML-2),由于其最近的整合,特别有趣.
研究的目的:
- 研究唤醒ERV在细胞衰老和生物衰老中的潜在作用.
- 确定HERVK激活是否有助于表型衰老.
- 探索针对老化中的ERV激活的治疗策略.
主要方法:
- 对人类衰老细胞基因表达的分析.
- 检测和描述由HERVK产生的复原病毒样颗粒 (RVLP).
- 使用中和抗体阻断HERVKRVPs的实验.
- 在老年动物模型 (灵长类动物,小鼠) 和人类组织中检查ERV激活.
- 评估ERV抑制对衰老和衰老标志物的影响.
主要成果:
- 人类衰老细胞表现出未锁定的HERVK转录和HERVKRVPs的产生.
- HERVK RVLP可以将衰老表型传递给年轻细胞.
- 中和抗体可以阻断HERVKRVPs的作用.
- 在老年灵长类动物和老鼠器官以及老年人组织和血清中观察到ERV激活.
- 抑制ERV可以减少细胞衰老,组织退化和生物老化.
结论:
- 内源逆转录病毒的重新激活,特别是HERVK,是细胞衰老和生物衰老的重要标志.
- 唤醒ERV是衰老的驱动力.
- 针对ERV的重新激活是缓解与年龄相关衰退的潜在治疗途径.
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