Brinkmann Vanessa, Ale-Agha Niloofar, Haendeler Judith, Ventura Natascia
IUF - Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany.
Institute of Clinical Chemistry and Laboratory Diagnostic, Medical Faculty, Heinrich Heine University of Düsseldorf, Düsseldorf, Germany.
Front Physiol. 2020 Jan 14;10:1561. doi: 10.3389/fphys.2019.01561. eCollection 2019.
Aging is the most important risk factor for the development of major life-threatening diseases such as cardiovascular disorders, cancer, and neurodegenerative disorders. The aging process is characterized by the accumulation of damage to intracellular macromolecules and it is concurrently shaped by genetic, environmental and nutritional factors. These factors influence the functionality of mitochondria, which play a central role in the aging process. Mitochondrial dysfunction is one of the hallmarks of aging and is associated with increased fluxes of ROS leading to damage of mitochondrial components, impaired metabolism of fatty acids, dysregulated glucose metabolism, and damage of adjacent organelles. Interestingly, many of the environmental (e.g., pollutants and other toxicants) and nutritional (e.g., flavonoids, carotenoids) factors influencing aging and mitochondrial function also directly or indirectly affect the activity of a highly conserved transcription factor, the Aryl hydrocarbon Receptor (AhR). Therefore, it is not surprising that many studies have already indicated a role of this versatile transcription factor in the aging process. We also recently found that the AhR promotes aging phenotypes across species. In this manuscript, we systematically review the existing literature on the contradictory studies indicating either pro- or anti-aging effects of the AhR and try to reconcile the seemingly conflicting data considering a possible dependency on the animal model, tissue, as well as level of AhR expression and activation. Moreover, given the crucial role of mitochondria in the aging process, we summarize the growing body of evidence pointing toward the influence of AhR on mitochondria, which can be of potential relevance for aging.
衰老是心血管疾病、癌症和神经退行性疾病等主要危及生命的疾病发生发展的最重要风险因素。衰老过程的特征是细胞内大分子损伤的积累，同时受到遗传、环境和营养因素的影响。这些因素影响线粒体的功能，而线粒体在衰老过程中起着核心作用。线粒体功能障碍是衰老的标志之一，与活性氧通量增加有关，活性氧通量增加会导致线粒体成分受损、脂肪酸代谢受损、葡萄糖代谢失调以及相邻细胞器受损。有趣的是，许多影响衰老和线粒体功能的环境因素（如污染物和其他有毒物质）和营养因素（如类黄酮、类胡萝卜素）也直接或间接影响一种高度保守的转录因子——芳烃受体（AhR）的活性。因此，许多研究已经表明这种多功能转录因子在衰老过程中发挥作用也就不足为奇了。我们最近还发现，AhR在不同物种中都能促进衰老表型。在本手稿中，我们系统地回顾了现有文献中关于AhR具有促衰老或抗衰老作用的矛盾研究，并试图考虑到可能依赖于动物模型、组织以及AhR表达和激活水平来调和这些看似相互矛盾的数据。此外，鉴于线粒体在衰老过程中的关键作用，我们总结了越来越多指向AhR对线粒体影响的证据，这可能与衰老具有潜在相关性。
