多基因分析揭示了更年期的时间,预测了前额叶皮层的衰老和认知功能
Fatima Gunter-Rahman1,2, Charleen D Adams3, Ravikiran M Raju4,5
1Harvard-MIT Program in Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Aging cell
|November 6, 2024
概括
更年期晚年 (AAM) 与更好的大脑衰老和认知功能有关. 这种卵巢衰老标志物可以预测痴呆症风险,肠道微生物组的变化起着作用.
科学领域:
- 神经科学是一个神经科学.
- 遗传学 是一个遗传学.
- 代谢学 代谢学 代谢学
背景情况:
- 痴呆症的诊断是频繁的,并且难以预测年龄以外的风险.
- 跨器官系统的衰老过程可能为早期痴呆症检测提供了洞察力.
- 识别早期生物标志物对于及时干预认知衰退至关重要.
研究的目的:
- 为了调查更年期的时间,卵巢衰老的标志物,预测大脑衰老和认知功能在以后的生活.
- 探索分子机制,包括遗传和代谢途径,将更年期 (AAM) 的年龄与大脑健康联系起来.
主要方法:
- 从2086名受试者的死后大脑样本中分析了"奥米克"数据 (基因组学,转录学,代谢学).
- 使用DNA甲基化计算前额叶皮层衰老加速.
- 检查基因表达和代谢物概况与更年期 (AAM) 的年龄和更年期类型 (自然与外科手术) 相比.
主要成果:
- 更年期晚年龄 (AAM) 与认知功能正相关,与大脑衰老加速负相关.
- 共享遗传性部分解释了AAM和认知功能之间的关联.
- 后来AAM与前额叶皮质的基因表达有关,与更好的认知和减少衰老途径 (自然更年期) 相关.
- 手术性更年期显示出明显的分子变化,包括改变的尼古丁胺氨酸二核酸 (NAD+) 活性和扰乱的胆酸代谢.
- 胆酸代谢在两个更年期组都发生了变化,与AAM相关的比例不同.
结论:
- 更年期的年龄 (AAM) 作为大脑衰老和认知功能的预测标记.
- 肠道微生物组可能会调解AAM和认知衰退之间的联系,自然与手术更年期的机制是不同的.
- 这些发现突出了痴呆风险评估的潜在早期生物标志物.
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