Faculty for Biosciences and Cluster of Excellence 'Macromolecular Complexes' Frankfurt, Institute of Molecular Biosciences, Johann Wolfgang Goethe University, Frankfurt, Germany.
Gerontology. 2013;59(5):413-20. doi: 10.1159/000348662. Epub 2013 Apr 18.
A fundamental impact of mitochondria on biological aging has been suggested decades ago. One prominent theory explains aging as the result of the age-related accumulation of random molecular damage of biomolecules resulting from the reaction of reactive oxygen species, the majority of which are generated in mitochondria. Although this concept appeared to be very attractive and strongly influenced aging research, in recent years more and more data accumulated which seem to contradict this theory. However, since these data are derived from reductionist approaches and do not integrate the various components and pathways which are affected as a result of a primary experimental intervention, they are prone to misinterpretation and have to be taken with some caution. Here, after a general introduction of mitochondrial function, we discuss the relevance of various pathways which are involved in keeping mitochondria functional over time. Moreover, we provide examples which emphasize the importance of a critical interpretation of experimental data and the necessity for a holistic analysis of the aging process. The success of such a systems biology approach is strongly dependent on the development of methods for data mining and an efficient analysis and modeling of the huge data sets that are raised.
几十年来,人们一直认为线粒体对生物衰老有根本性的影响。一个著名的理论解释了衰老,即随着年龄的增长,生物分子随机分子损伤的积累,这是由于活性氧物质的反应造成的,其中大部分是在线粒体中产生的。尽管这个概念似乎非常有吸引力,并强烈影响了衰老研究,但近年来,越来越多的数据积累起来,这些数据似乎与这一理论相矛盾。然而,由于这些数据是从还原论的方法中得出的,并没有整合由于主要实验干预而受到影响的各种成分和途径,因此它们容易被误解,需要谨慎对待。在这里,在介绍了线粒体的一般功能之后,我们讨论了随着时间的推移,参与保持线粒体功能的各种途径的相关性。此外,我们提供了一些例子,强调了对实验数据进行批判性解释的重要性,以及对衰老过程进行整体分析的必要性。这种系统生物学方法的成功在很大程度上取决于数据挖掘方法的发展,以及对所产生的庞大数据集进行有效分析和建模的能力。