Division of Neurodegenerative Disorders, St. Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB, Canada.
Mitrix Bio INC, Pleasanton, CA, USA.
Mol Neurobiol. 2022 Oct;59(10):6009-6017. doi: 10.1007/s12035-022-02937-w. Epub 2022 Jul 14.
The mitochondrial theory of aging is characterized by mitochondrial electron transport chain dysfunction. As a hallmark of aging, an increasing number of investigations have attempted to improve mitochondrial function in both aging and age-related disease. Emerging from these attempts, methods involving mitochondrial isolation, transfusion, and transplantation have taken center stage. In particular, mitochondrial transfusion refers to the administration of mitochondria from healthy tissue into the bloodstream or into tissues affected by injury, disease, or aging. In this study, methods of mitochondrial isolation and transfusion were developed and utilized. First, we found a significant decrease (p < 0.05) in the expression of mitochondrial complex proteins (I-V) in aged (12 months old) mouse brain tissue (C57BL/6 mice) in comparison to healthy young brain tissue (1 month old). To investigate whether healthy young mitochondria taken from the liver could improve mitochondrial function in older animals, we intravenously injected mitochondria isolated from young C57BL/6 mice into aged mice from the same strain. This study, for the first time, demonstrates that mitochondrial transfusion significantly (p < 0.05) improves mitochondrial function via the up-regulation of the mitochondrial complex II protein subunit SDHB in the hippocampus of aged mice. This result has identified a role for mitochondrial complex II in the aging process. Therefore, mitochondrial complex II could serve as a putative target for therapeutic interventions against aging. However, more importantly, methods of mitochondrial transfusion should be further tested to treat a variety of human diseases or disorders and to slow down or reverse processes of aging.
衰老的线粒体理论的特点是线粒体电子传递链功能障碍。作为衰老的一个标志，越来越多的研究试图改善衰老和与年龄相关的疾病中的线粒体功能。在这些尝试中，涉及线粒体分离、输血和移植的方法占据了中心地位。特别是，线粒体输血是指将来自健康组织的线粒体输入血液或输入受伤、患病或衰老的组织。在这项研究中，开发并利用了线粒体分离和输血的方法。首先，我们发现与年轻健康脑组织（1 个月大）相比，衰老（12 个月大）的小鼠脑组织（C57BL/6 小鼠）中线粒体复合物蛋白（I-V）的表达显著降低（p<0.05）。为了研究从肝脏中提取的健康年轻线粒体是否可以改善老年动物的线粒体功能，我们将从小鼠肝脏中分离出的年轻 C57BL/6 小鼠的线粒体静脉注射到来自同一品系的老年小鼠体内。这项研究首次表明，线粒体输血通过上调老年小鼠海马体中线粒体复合物 II 蛋白亚基 SDHB，显著（p<0.05）改善了线粒体功能。这一结果确定了线粒体复合物 II 在衰老过程中的作用。因此，线粒体复合物 II 可作为治疗衰老的潜在靶点。然而，更重要的是，线粒体输血的方法应该进一步测试，以治疗各种人类疾病或障碍，并减缓或逆转衰老过程。
