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端粒长度和椎间盘退化之间的因果关系和代谢调解:一个双阶段网络门德尔随机化研究

Cheng Qin¹, Xiangming Li, Mingyue Xiong

¹Department of Orthopedics, First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan, China.

|March 6, 2026

概括

较长的端粒长度 (TL) 提供了对椎间盘退化 (IVDD) 的保护. 氨基酸氨酸部分介导这种保护作用,这表明脊柱健康的新干预目标.

科学领域:

遗传学是一个遗传学.
衰老研究研究衰老研究
代谢学代谢学代谢学

背景情况:

椎间盘退化 (IVDD) 是腰部疼痛的主要原因,衰老是显著的危险因素.
生物衰老标志物的直接作用,如端粒长度 (TL),以及IVDD的潜在代谢途径尚未得到充分理解.

研究的目的:

使用孟德尔随机化方法,研究端粒长度 (TL) 对椎间盘退化 (IVDD) 风险的因果关系.
探索TL和IVDD之间的关系中的潜在代谢媒介,特别是循环血液中的代谢物.

主要方法:

使用了2个样本的门德尔随机化 (MR) 框架,以及全基因组关联研究总结数据.
雇佣链接不平衡得分回归 (LDSC) 来评估TL和IVDD之间的遗传相关性.
进行了网络MR调解分析,以确定调解TL-IVDD关联的代谢物.

主要成果:

对MR的分析表明,较长的TL对IVDD具有显著的保护性因果作用 (OR=0.883).
LDSC发现TL和IVDD之间存在显著的负遗传相关性 (rg=-0.1409).
鉴定了16种介导代谢物,其中氨酸显示出最显著的效果;较长的TL与较低的氨酸相关,而较高的氨酸与IVDD风险增加有关.

结论:

提供了强有力的遗传证据,表明较长的端粒长度 (TL) 与脊椎间盘退化 (IVDD) 的风险降低有关.
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建议端粒维护和氨基酸代谢,特别是氨酸,作为IVDD早期干预的潜在目标.

关键词:

门德尔的随机化衰老的衰老衰老的衰老椎间盘退化椎间盘退化代谢生物组的代谢生物组端粒的长度端粒的长度泰洛辛 (tyrosine) 是一种蛋白质.

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