Chu Xiaogang, Subramani Kumar, Thomas Bobby, Terry Alvin V, Fulzele Sadanand, Raju Raghavan Pillai
1Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta, GA 30912, USA.
2Departments of Pediatrics, Neuroscience and Drug Discovery, Darby Children's Research Institute, Medical University of South Carolina, Charleston, SC 29425, USA.
Aging Dis. 2022 Apr 1;13(2):568-582. doi: 10.14336/AD.2021.0830. eCollection 2022 Apr.
Studies have shown that factors in the blood of young organisms can rejuvenate the old ones. Studies using heterochronic parabiosis models further reinforced the hypothesis that juvenile factors can rejuvenate aged systems. We sought to determine the effect of juvenile plasma-derived factors on the outcome following hemorrhagic shock injury in aged mice. We discovered that pre-pubertal (young) mice subjected to hemorrhagic shock survived for a prolonged period, in the absence of fluid resuscitation, compared to mature or aged mice. To further understand the mechanism of maturational dependence of injury resolution, extracellular vesicles isolated from the plasma of young mice were administered to aged mice subjected to hemorrhagic shock. The extracellular vesicle treatment prolonged life in the aged mice. The treatment resulted in reduced oxidative stress in the liver and in the circulation, along with an enhanced expression of the nuclear factor erythroid factor 2-related factor 2 (Nrf2) and its target genes, and a reduction in the expression of the transcription factor BTB and CNC homology 1 (Bach1). We propose that plasma factors in the juvenile mice have a reparative effect in the aged mice in injury resolution by modulating the Nrf2/Bach1 axis in the antioxidant response pathway.
研究表明，年轻生物体血液中的因子可以使衰老生物体恢复活力。使用异时联体共生模型的研究进一步强化了这一假说，即年轻因子可以使衰老系统恢复活力。我们试图确定源自幼年血浆的因子对老年小鼠失血性休克损伤后结局的影响。我们发现，与成熟或老年小鼠相比，遭受失血性休克的青春期前（年轻）小鼠在没有液体复苏的情况下存活时间更长。为了进一步了解损伤修复成熟依赖性的机制，将从小鼠血浆中分离出的细胞外囊泡给予遭受失血性休克的老年小鼠。细胞外囊泡治疗延长了老年小鼠的寿命。该治疗导致肝脏和循环系统中的氧化应激降低，同时核因子红细胞相关因子2（Nrf2）及其靶基因的表达增强，转录因子BTB和CNC同源物1（Bach1）的表达降低。我们提出，幼年小鼠的血浆因子通过调节抗氧化反应途径中的Nrf2/Bach1轴，在老年小鼠损伤修复中具有修复作用。
