增强的补充剂延长寿命,并通过通过维持平衡来调节Sik1通路来延迟多器官的衰老
Yang Yu1,2, Jintao Song1,2, Mengjiao Guo1,2
1Health Sciences Institute, China Medical University, Shenyang, Liaoning, 110122, China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|October 2, 2025
概括
新的纳米粒子 (SeMSNs) 通过减少氧化应激和改善小鼠的健康状况来对抗衰老. 这些纳米粒子在治疗与年龄有关的疾病方面,比传统的补充剂提供了更好的生物可用性和有效性.
科学领域:
- 生物材料科学 生物材料科学
- 纳米技术纳米技术
- 衰老研究研究 衰老研究
背景情况:
- 补充剂对与衰老相关的疾病有希望,但面临生物可用性和治疗疗效方面的挑战.
- 现有的输送系统在有效向老化机制方面存在局限性.
研究的目的:
- 开发和评估氧化还原-双响应的二化物桥架的半孔纳米颗粒 (SeMSNs) 作为一种先进的纳米疗法,用于抗衰老.
- 调查SeMSNs在减少氧化应激,抑制细胞衰老和改善与年龄相关的条件 in vitro 和 in vivo 的有效性.
主要方法:
- 合成SeMSN及其氧化还原反应性质的表征.
- 在老鼠胚胎纤维细胞和H2O2处理的HEK-293T细胞中,评估SeMSN在降低氧化应激和衰老标志物 (p16,p21) 的有效性.
- 在体内对老年小鼠进行研究,以评估寿命,脆弱性,器官功能 (肌肉,脏,肝脏),认知性能和代谢平衡.
- 涉及蛋白表达,内网膜应激,平衡和NFATc2-Sik1信号通路的机制研究.
- 将SeMSN与商业中的甲,常规的半孔纳米粒子 (MSN) 和二硫化物桥接MSN (SMSN) 进行比较.
主要成果:
- 与氨酸相比,SeMSNs表现出优越的抗氧化作用和降低细胞毒性.
- 在老年小鼠中,SeMSN显著延长了寿命,减少了脆弱性,改善了肌肉缩,功能障碍,认知衰退和肝硬化.
- 在改善与年龄有关的条件方面,SeMSN的表现优于传统的MSN和SMSN.
- 机理学调查显示,SeMSN介导的蛋白调节,抑制ER压力,维持平衡,以及抑制NFATc2-Sik1信号传递,导致p21/p16表达减少.
- 临床数据显示,水平与衰老生物标志物之间存在逆相关性.
- 在人类脂肪原生细胞中,SeMSN恢复了脂肪原体的分化.
结论:
- 与传统的形式相比,红氧双响应的SeMSN代表了对抗多器官衰老的优越纳米治疗策略.
- 通过调节关键分子通路,SeMSN有效抑制细胞衰老,并改善各种与年龄相关的生理功能障碍.
- 这种纳米技术在促进健康长寿和治疗与年龄有关的疾病方面具有显著的潜力.
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