衰老会触发心脏中的线粒体,内质网膜和代谢应激反应
Sakthijothi Muthu1, Zinnia Tran1, Jayapalraja Thilagavathi2
1Department of Physiology, Pharmacology and Toxicology, School of Medicine, West Virginia University, Morgantown, WV 26506, USA.
概括
心脏衰老诱导线粒体和ER压力,导致氧化损伤和细胞衰竭. 这些途径是与年龄有关的心脏功能障碍的潜在治疗点.
科学领域:
- 心血管生物学 心血管生物学
- 细胞衰老 细胞衰老
- 线粒体生物学 线粒体生物学
背景情况:
- 老龄化逐渐损害细胞和组织功能,特别是影响心血管系统,增加心血管疾病的风险.
- 线粒体 (mt) 和内质网膜 (ER) 对于心脏平衡和能量产生至关重要,但它们在心脏衰老中的作用尚未完全理解.
研究的目的:
- 为了研究心脏衰老中的线粒体和ER应激反应.
- 探索心脏衰老中相关的代谢,细胞和自压力因素.
主要方法:
- 利用10个月和25个月大的CBA/CaJ小鼠来评估mt,ER,代谢,细胞和自压力.
- 分析了线粒体生物发生,压力反应,自,代谢标记物和转录因子的基因表达.
- 测量了氧化损伤标志物,如4-HNE.
主要成果:
- 衰老的心脏表现出特定的mt基因 (mt-Cytb,mt-Co2) 和压力蛋白酶 (Lonp1,Yme1l1,Afg3l2,Spg7,Clpp,Clpx) 的诱导表达,以及诱导的mt共同伴侣Dnaja2.2.
- 诱导了ER应激转录因子 (Xbp1,Atf6),减少了Hsp90b的表达,改变了线粒体动力学 (Dnm1l诱导,Mfn1/Fis1下调).
- 没有观察到自/代谢调节者的显著变化,但老年心脏中氧化损伤 (4-HNE) 增加.
结论:
- 心脏衰老会引发线粒体,ER和氧化应激.
- 这导致心脏中累积的氧化损伤和细胞损伤.
- 这些途径代表了减轻与年龄有关的心脏功能障碍的潜在治疗点.
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