多omics揭示了与老化相关的自然老化老鼠肝脏的途径
Cong-Min Tang1,2,3, Zhen Zhang1,4, Yan Sun1
1Department of Geriatric Medicine, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China.
Heliyon
|November 3, 2023
概括
衰老会改变肝脏的结构和功能,影响代谢物和蛋白质. 这项研究在小鼠中使用代谢学和蛋白学来揭示与衰老相关的肝脏变化及其与癌症途径的联系.
科学领域:
- 老年学和分子生物学
- 肝脏病理生理学肝脏病理生理学
- 多主题研究 多主题研究
背景情况:
- 衰老导致肝脏的结构和功能逐渐发生变化,包括改变的代谢物和细胞功能.
- 与衰老相关的肝脏变化的特定表型及其潜在机制仍然不清楚.
- 高通量欧米克技术为了解衰老过程提供了新的途径.
研究的目的:
- 与年轻小鼠相比,在自然老化小鼠的肝脏中识别改变的代谢物和酸化蛋白质.
- 发现与肝脏衰老相关的新生物标志物和途径.
- 揭示与衰老和肝脏病理有关的生物机制,包括与癌症的潜在联系.
主要方法:
- 应用代谢学和蛋白学对年轻 (WTY) 和老年 (WTA) 小鼠的肝脏样本.
- 进行了组织学和电子显微镜,以评估肝脏组织损伤.
- 利用西方斑点来验证蛋白质表达变化.
主要成果:
- 年龄较大的小鼠显示体重增加,氨酸转移酶 (ALT) 和亚斯巴酸转移酶 (AST),握力降低.
- 肝脏组织表现出纤维化,炎症,肝细胞退化,脂质和糖原沉积,线粒体损伤和缩小内分泌网膜.
- 多基因组分析显示,老年肝脏的新陈代谢和蛋白质路径发生变化,热冲击蛋白HSP 90-alpha (HSP90A) 和v-raf鼠病毒瘤基因同类B1 (BRAF) 的升高调节,这涉及癌症路径. 下游的MEK和ERK蛋白质也升高.
结论:
- 衰老显著影响肝脏结构和功能,其特点是特定的代谢和蛋白质基因变化.
- 该研究确定了关键的途径和蛋白质,包括与癌症相关的蛋白质,这些蛋白质在自然肝脏衰老过程中受到失调.
- 这些发现突出了衰老和癌症发展之间的潜在联系,并增强了对衰老中的多种变化的理解.
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