在社区动脉样硬化风险研究 (ARIC) 中,蛋白质老化时钟的发展和表征
Shuo Wang1, Zexi Rao2, Rui Cao2
1Department of Laboratory Medicine and Pathology, Medical School, University of Minnesota, Minneapolis, MN.
medRxiv : the preprint server for health sciences
|September 21, 2023
概括
在一个大而多元的队列中开发的新型蛋白质衰老时钟 (PAC) 显示了与现有的时钟相似的死亡率关联. 这些发现表明,PAC可以预测死亡风险,这需要在不同人群中进行进一步的研究.
科学领域:
- 衰老的生物标志物
- 蛋白质组学是指蛋白质组学.
- 流行病学 流行病学
背景情况:
- 使用蛋白质衰老钟 (PAC) 估计生物年龄是一个新兴领域.
- 现有的PAC有其局限性,包括样本规模小,缺乏多样性和单个时间点的测量.
- 社区动脉样硬化风险 (ARIC) 研究提供了一个独特的机会,在一个大,纵向和多样化的队列中开发和验证PAC.
研究的目的:
- 利用ARIC研究的数据开发新的蛋白质衰老时钟 (PAC).
- 将这些新型PAC与以前发布的PAC的表现进行比较.
- 评估PACs及其随时间变化与所有原因,心血管疾病 (CVD),癌症和下呼吸道疾病 (LRD) 死亡率的关联.
主要方法:
- 使用SomaScan测量了11,761名中年和5,183名晚年ARIC参与者的血蛋白质水平 (4,712种蛋白质).
- 在健康的参与者中,使用弹性净回归来训练de novoPACs以计时年龄.
- 估计了年龄加速及其从中年到晚年生活的变化,并使用Cox比例危险回归来估计并与死亡率相关,并对混因素进行调整.
主要成果:
- 在ARIC开发的PAC显示出与时间年龄的相关性略强,而不是在健康人群中发表的PAC.
- 无论是ARIC还是已发表的PAC,都显示出与所有原因,心血管疾病和LRD死亡率的类似关联.
- 更高的年龄加速,特别是从中年到晚年的生活的变化,与多种原因的死亡风险增加有显著的关联.
结论:
- 在ARIC研究中开发的新型蛋白质衰老时钟的性能与现有的PAC相美.
- 新的和已发表的PAC都与增加的死亡风险有关,强调它们作为预后标志物的有用性.
- 建议在多种人群中进行进一步的研究和验证,以便对PAC进行高级测试和应用.
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