通过自消化的衰老
Frank A DeLano1, Geert W Schmid-Schönbein1
1Shu Chien-Gene Ley Department of Bioengineering, Center for Autodigestion Innovation, University of California San Diego, La Jolla, California, United States of America.
PloS one
|October 17, 2024
概括
衰老的组织分解可能源于从肠道泄漏的消化酶. 在老老鼠中阻断胰腺素减少了酶积累,原损伤和高血糖症.
科学领域:
- 生物遗传学 生物遗传学
- 消化系统生理学 消化系统生理学
- 分子生物学分子生物学
背景情况:
- 驱动与年龄相关的细胞功能障碍,炎症和组织降解的机制在很大程度上是未知的.
- 在胰腺中合成的消化酶通常被粘膜/上皮屏障限制在小肠的光层中.
研究的目的:
- 为了研究一种新的假设,即与衰老相关的组织分解是由来自胃肠道泄漏的消化酶的自消化引起的.
- 检查胰腺酶在与年龄相关的组织损伤和代谢功能障碍中的作用.
主要方法:
- 免疫组织化学被用来检测胰腺酶 (素,弹性酶,脂酶,粉酶) 在年轻和老老鼠的外周器官.
- 对小肠粘素层密度和从小肠泄漏的酶泄漏的分析.
- 在老化组织中评估原蛋白损伤和胰岛素受体裂变.
- 治疗老老鼠用胺酸,一种血清蛋白酶抑制剂,以阻止胰腺素.
主要成果:
- 与年轻大鼠相比,在老老鼠的外周器官中观察到胰腺酶的大量积累.
- 老老鼠表现出减弱的粘素层密度和素从肠道小泄漏.
- 在老老鼠中,原蛋白损伤和胰岛素受体细胞外域的蛋白质分解裂变是普遍存在的.
- 在老老的老鼠中,素酸治疗减少了酶积累,原损伤,高血糖和胰岛素受体裂变.
结论:
- 衰老过程中的组织分解可能是由于过早激活的消化酶的自消化造成的.
- 肠道屏障的完整性对于防止系统性酶泄漏和与年龄有关的损伤至关重要.
- 向胰腺酶活性,例如用血清蛋白酶抑制剂,显示了减轻与衰老相关的病态的潜力.
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