Signorile Anna, De Rasmo Domenico
Department of Translational Biomedicine and Neuroscience, University of Bari Aldo Moro, 70124 Bari, Italy.
Institute of Biomembranes, Bioenergetics and Molecular Biotechnology (IBIOM), National Research Council (CNR), 70126 Bari, Italy.
Antioxidants (Basel). 2023 Jan 18;12(2):221. doi: 10.3390/antiox12020221.
In mammals during aging, reactive oxygen species (ROS), produced by the mitochondrial respiratory chain, cause oxidative damage of macromolecules leading to respiratory chain dysfunction, which in turn increases ROS mitochondrial production. Many efforts have been made to understand the role of oxidative stress in aging and age-related diseases. The complex I of the mitochondrial respiratory chain is the major source of ROS production and its dysfunctions have been associated with several forms of neurodegeneration, other common human diseases and aging. Complex I-ROS production and complex I content have been proposed as the major determinants for longevity. The cAMP signal has a role in the regulation of complex I activity and the decrease of ROS production. In the last years, an increasing number of studies have attempted to activate cAMP signaling to treat age-related diseases associated with mitochondrial dysfunctions and ROS production. This idea comes from a long-line of studies showing a main role of cAMP signal in the memory consolidation mechanism and in the regulation of mitochondrial functions. Here, we discuss several evidences on the possible connection between complex I and cAMP pathway in the aging process.
在哺乳动物衰老过程中，线粒体呼吸链产生的活性氧（ROS）会导致大分子的氧化损伤，进而导致呼吸链功能障碍，这反过来又会增加线粒体ROS的产生。人们已经做出了许多努力来理解氧化应激在衰老和与年龄相关疾病中的作用。线粒体呼吸链的复合体I是ROS产生的主要来源，其功能障碍与多种形式的神经退行性变、其他常见人类疾病和衰老有关。复合体I-ROS的产生和复合体I的含量被认为是长寿的主要决定因素。cAMP信号在复合体I活性的调节和ROS产生的减少中起作用。在过去几年中，越来越多的研究试图激活cAMP信号来治疗与线粒体功能障碍和ROS产生相关的年龄相关疾病。这个想法源于一系列长期研究，这些研究表明cAMP信号在记忆巩固机制和线粒体功能调节中起主要作用。在这里，我们讨论了关于衰老过程中复合体I与cAMP途径之间可能联系的几个证据。
