Baranov Vladislav S, Baranova Elena V
Ott's Research Institute of Obstetrics, Gynecology & Reproduction, ul. Mendeleevskaya Liniya 3, St. Petersburg, 199034, Russia.
Curr Aging Sci. 2017;10(1):6-11. doi: 10.2174/1874609809666160921114504.
Famous Free Radical Theory (FRT) of aging, the 50th year anniversary of which is celebrated in 2015 postulates a crucial role of Reactive Oxygen Species (ROS) in aging. Still it is the most robust theory of aging as mitochondria ROS production (mtROSp) correlates well with four principal ''rules" of aging being universal, endogenous, progressive, and deleterious. Vast number of experiments in different species prove mutagenic effect of ROS and their carcinogenic properties. So far, FRT stimulates the search of new pharmaceuticals with antioxidant activity. However, some recent experimental data and clinical findings render doubt to ROS as a principal senescence drivers and come in conflict with original version of FRT. Growth stimulating effects of ROS and their modest antitumor properties support these objections. One should remember that FRT is only one of the numerous theories of aging. Molecular mechanisms of senescence involve all living systems and numerous metabolic pathways which are also variable owing to the unique properties of individual genome and unique epigenetic modulations operating throughout the lifetime thus making aging a unique private matter. Universal theory of aging that incorporates and explains all known and suggested mechanisms of aging, is illusive. However, knowledge of unique peculiarities of individual genome, its feasible editing and efficient epigenetic regulation of metabolic pathways give a chance to postpone aging and extend period of active longevity.
著名的衰老自由基理论（FRT）认为活性氧（ROS）在衰老过程中起关键作用，2015年是该理论提出50周年。它仍是最具影响力的衰老理论，因为线粒体ROS生成（mtROSp）与衰老的四个主要“规则”密切相关，即普遍性、内源性、渐进性和有害性。大量针对不同物种的实验证明了ROS的诱变作用及其致癌特性。到目前为止，FRT推动了对抗氧化活性新药的探索。然而，最近的一些实验数据和临床发现对ROS作为主要衰老驱动因素提出了质疑，并与FRT的原始版本产生了冲突。ROS的生长刺激作用及其适度的抗肿瘤特性支持了这些反对意见。应该记住，FRT只是众多衰老理论之一。衰老的分子机制涉及所有生命系统和众多代谢途径，由于个体基因组的独特性质和一生中独特的表观遗传调控，这些途径也是可变的，因此衰老成为一个独特的个体问题。包含并解释所有已知和提出的衰老机制的通用衰老理论是虚幻的。然而，了解个体基因组的独特特性、可行的编辑以及对代谢途径的有效表观遗传调控，为延缓衰老和延长积极寿命提供了机会。
