减少双链DNA断裂修复加剧了血管衰老
Samuel I Bloom1, Jordan R Tucker2, Daniel R Machin3
1Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, UT 84148, USA.
Aging
|October 3, 2023
概括
衰老加速动脉功能障碍和心血管疾病 (CVD) 风险,通过增加动脉中的DNA损伤. 这项研究揭示了老年动脉中DNA损伤积累如何损害血管功能,导致心血管疾病的发展.
科学领域:
- 心血管生物学 心血管生物学
- 衰老研究研究 衰老研究
- 分子生物学分子生物学
背景情况:
- 高龄是心血管疾病 (CVD) 的主要危险因素.
- 随着年龄的增长,动脉功能受损有助于心血管疾病的发展.
- 与年龄相关的动脉功能障碍中DNA损伤的作用尚未得到充分研究.
研究的目的:
- 调查在衰老过程中动脉中DNA损伤的发生率和生理后果,特别是微血管.
- 探索DNA损伤积累和与年龄相关的动脉功能障碍之间的联系.
主要方法:
- 评估了人类和小鼠肺部微血管内皮细胞中的DNA损伤.
- 在具有不同ATM激酶水平 (DNA修复蛋白) 的小鼠中评估了内皮功能,微血管/葡萄糖特性和动脉硬性.
- 将老化野生型小鼠与老化ATM+/-小鼠进行比较 (对ATM激酶有异性).
主要成果:
- 衰老增加了微血管内皮细胞中的DNA损伤.
- 老年ATM+/-小鼠表现出加快的血管衰老,与增加的动脉DNA损伤,衰老信号和受损的内皮依赖扩张.
- 与对照组相比,老ATM+/-小鼠的微血管密度降低,葡萄糖体变薄,动脉硬性增加.
结论:
- 在晚年期间动脉中积累的DNA损伤对动脉功能障碍有显著的贡献.
- 这种与年龄相关的动脉功能障碍是心血管疾病发展的关键驱动因素.
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