Schniertshauer Daniel, Gebhard Daniel, Bergemann Jörg
Department of Life Sciences, Albstadt-Sigmaringen University of Applied Sciences, 72488 Sigmaringen, Germany.
J Aging Res. 2018 Sep 5;2018:6354680. doi: 10.1155/2018/6354680. eCollection 2018.
The process of aging is characterized by the increase of age-associated disorders as well as severe diseases. Due to their role in the oxidative phosphorylation and thus the production of ATP which is crucial for many cellular processes, one reason for this could be found in the mitochondria. The accumulation of reactive oxygen species damaged mitochondrial DNA and proteins can induce mitochondrial dysfunction within the electron transport chain. According to the "mitochondrial theory of aging," understanding the impact of harmful external influences on mitochondrial function is therefore essential for a better view on aging in general, but the measurement of mitochondrial respiration in skin cells from cell cultures cannot completely reflect the real situation in skin. Here, we describe a new method to measure the mitochondrial respiratory parameters in epithelial tissue derived from human skin biopsies using a XF24 extracellular flux analyzer to evaluate the effect of coenzyme Q10. We observed a decrease in mitochondrial respiration and ATP production with donor age corresponding to the "mitochondrial theory of aging." For the first time in human epidermis, we could show also a regeneration of mitochondrial respiratory parameters if the reduced form of coenzyme Q10, ubiquinol, was administered. In conclusion, an age-related decrease in mitochondrial respiration and ATP production was confirmed. Likewise, an increase in the respiratory parameters by the addition of coenzyme Q10 could also be shown. The fact that there is a significant effect of administered coenzyme Q10 on the respiratory parameters leads to the assumption that this is mainly caused by an increase in the electron transport chain. This method offers the possibility of testing age-dependent effects of various substances and their influence on the mitochondrial respiration parameters in human epithelial tissue.
衰老过程的特征是与年龄相关的疾病以及严重疾病的增加。由于线粒体在氧化磷酸化以及ATP生成中所起的作用,而ATP对许多细胞过程至关重要,因此衰老的一个原因可能在于线粒体。活性氧的积累会破坏线粒体DNA和蛋白质,从而诱导线粒体电子传递链功能障碍。根据“衰老的线粒体理论”,了解有害外部影响对线粒体功能的作用,对于从总体上更好地理解衰老至关重要,但是通过细胞培养来测量皮肤细胞中的线粒体呼吸并不能完全反映皮肤的真实情况。在此,我们描述了一种新方法,使用XF24细胞外通量分析仪测量源自人类皮肤活检组织的上皮组织中的线粒体呼吸参数,以评估辅酶Q10的作用。我们观察到,线粒体呼吸和ATP生成随供体年龄的增加而减少,这与“衰老的线粒体理论”相符。在人类表皮中,我们首次发现,如果给予还原型辅酶Q10(泛醇),线粒体呼吸参数也会恢复。总之,我们证实了线粒体呼吸和ATP生成随年龄增长而减少。同样,添加辅酶Q10也能使呼吸参数增加。所给予的辅酶Q10对呼吸参数有显著影响,这一事实使我们推测,这主要是由电子传递链的增加所致。该方法为测试各种物质的年龄依赖性效应及其对人类上皮组织中线粒体呼吸参数的影响提供了可能。