活性维生素D不足通过氧化应激和p16介导衰老加速骨衰老
Wanxin Qiao1, Mingxin Huang1, Lulu Chen1
1The Research Center for Bone and Stem Cells, Department of Anatomy, Histology and Embryology, Nanjing Medical University, 211166 Nanjing, Jiangsu, China.
Frontiers in bioscience (Landmark edition)
|January 8, 2026
概括
维生素D不足通过增加氧化应激和衰老,加速骨衰老. 抗氧化剂,维生素D或p16抑制等治疗方法改善了小鼠的骨健康和存活率.
科学领域:
- 生物遗传学 生物遗传学
- 分子生物学分子生物学
- 骨生物学 骨生物学
背景情况:
- 维生素D对骨健康至关重要,但其对衰老过程的影响,如氧化还原平衡和细胞衰老,尚未完全理解.
- 研究维生素D缺乏和加速衰老之间的联系对于了解与年龄相关的骨质损失至关重要.
研究的目的:
- 为了确定活性维生素D缺乏是否通过氧化应激和衰老途径加速骨质损失.
- 探索p16瘤抑制蛋白在维生素D缺乏引起的骨老化的作用.
主要方法:
- 使用了野生型和Cyp27b1哈普洛因缺乏的雄性小鼠,模拟维生素D缺乏.
- 服用了N-乙半氨酸 (NAC) 或1,25-二氧维生素D3 [1,25(OH) 2D3],并评估了寿命,氧化应激,DNA损伤,衰老标志物和骨微型结构.
- 采用p16淘汰模型来评估p16在观察到的影响中的特定作用.
主要成果:
- 在Cyp27b1+/-小鼠中,维生素D缺乏导致寿命缩短,氧化应激增加,DNA损伤,衰老和骨体积减少.
- 用NAC或1,25(OH) 2D3治疗显著改善了生存率,减少了氧化应激和衰老,增加了骨体积.
- 在维生素D不足的小鼠中,p16的遗传删除也改善了骨体积,并减少了衰老标志物.
结论:
- 活性维生素D不足通过涉及活性氧物种,DNA损伤和p16/衰老的途径加速骨衰老.
- 抗氧化剂,维生素D补充或p16抑制可以挽救与维生素D缺乏相关的骨损失.
- 准氧化还原衰老路径为骨质疏松症提供了潜在的治疗策略.
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