肝脏特定的表型衰老,行为和遗传风险,以及与肝脏有关的长期结果
Tianhao Wu1,2, Chengnan Guo3, Huangbo Yuan2,4
1Human Phenome Institute, Research and Innovation Center, Shanghai Pudong Hospital, Fudan University, Shanghai, 200433, China.
GeroScience
|January 28, 2026
概括
研究人员使用临床标志物开发了一种肝脏特定的表型年龄 (PhenoAgeAccel). 这种新的衰老指标预测肝病风险和死亡率,为有针对性的预防策略提供了潜力.
科学领域:
- 老年学和衰老研究研究.
- 肝病学和肝脏疾病.
- 生物标志物发现和验证
背景情况:
- 现型年龄,一个基于生物标志物的衰老指标,与疾病和死亡率相关.
- 目前缺乏肝脏衰老及其临床影响的具体指标.
- 了解肝脏衰老机制对于预测肝脏相关结果至关重要.
研究的目的:
- 开发和验证肝脏特定的表型年龄指标.
- 评估肝脏特异性表型衰老加速 (PhenoAgeAccel) 与长期肝脏结果和死亡率的关联.
- 探索肝脏特异性PhenoAgeAccel在风险行为和肝脏健康之间的关系中的调解作用.
主要方法:
- 在英国生物库 (英格兰-白队伍) 中使用11个临床血液标志物的肝脏特异性表型年龄的开发.
- 在独立队列 (苏格兰-威尔士和非白人-英国) 中验证.
- 使用蛋白质和代谢分析计算PhenoAgeAccel并检查与死亡率,肝脏事件和风险行为的关联.
主要成果:
- 肝脏特异性PhenoAgeAccel显著增加了所有原因死亡率和肝脏事件的风险 (1.23至2.97倍).
- 关联在男性和具有高遗传风险的个体中更强,超过了系统性PhenoAgeAccel的关联.
- 肝脏特异性PhenoAgeAccel调解了风险行为和肝脏结果之间的联系的10-27%,已识别的肝脏丰富蛋白质 (例如,AGXT,SULT2A1) 发挥了作用.
结论:
- 肝脏特定的PhenoAgeAccel是肝脏相关结果和死亡率的强有力的预测指标.
- 这一指标部分调解了可修改行为对肝脏健康的影响.
- 这些发现表明,肝脏特定的PhenoAgeAccel可以增强风险分层,并为肝脏衰老的预防策略提供信息.
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