用菲塞治疗可逆转与年龄相关的内皮功能障碍,部分由SASP因子CXCL12介导
Sophia A Mahoney1, Krystyna Mazan-Mamczarz2, Dimitrios Tsitsipatis3
1Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO.
bioRxiv : the preprint server for biology
|September 2, 2025
概括
细胞衰老导致与年龄相关的心血管疾病, 通过向与衰老相关的分泌表型 (SASP) 和CXCL12信号,老化药物fisetin可以逆转这种损伤.
科学领域:
- 心血管生物学
- 老龄化研究
- 细胞衰老
背景情况:
- 老龄化是心血管疾病 (CVD) 的主要危险因素,与血管内皮功能失调有关.
- 细胞衰老及其相关的分泌表型 (SASP) 通过氧化应激和炎症加剧内皮功能障碍,降低氧化 (NO) 的生物可用性.
- 内皮细胞衰老和与衰老相关的功能障碍背后的分子机制需要进一步阐明.
研究的目的:
- 确定内皮细胞衰老相关的信号通路.
- 描述导致衰老的内皮衍生SASP因素.
- 研究这些因素对衰老中的内皮功能的影响.
主要方法:
- 从年轻和老小鼠的小鼠大动脉单细胞转录组,有或没有费塞丁治疗.
- 测量循环SASP因子与转录变化相关.
- 使用分离的小鼠动脉和培养的人体内皮细胞进行体外实验,以评估血环境和特定SASP因子的影响.
主要成果:
- 衰老的内皮细胞表现出SASP因子表达的增加,特别是CXCL12,而这种表达被菲塞丁逆转.
- 循环中的CXCL12水平反映了这些转录变化.
- 老鼠血诱导了血管衰老,降低了NO,增加了氧化应激,并促进了内皮转移到介质细胞,部分由CXCL12调节,并被fisetin缓解.
结论:
- SASP和CXCL12被确定为与年龄相关的内皮功能障碍的关键驱动因素.
- 通过补充费塞的老化干预机制已经确立.
- 这项研究提供了针对细胞衰老的洞察力,
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