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褪黑素相关氧化还原稳态、衰老与昼夜节律的整合

Integration of Melatonin Related Redox Homeostasis, Aging, and Circadian Rhythm.

作者信息

Yanar Karolin, Simsek Bahadir, Çakatay Ufuk

机构信息

Department of Medical Biochemistry, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey.

出版信息

Rejuvenation Res. 2019 Oct;22(5):409-419. doi: 10.1089/rej.2018.2159. Epub 2019 Feb 4.

DOI:10.1089/rej.2018.2159
PMID:30595087
Abstract

Circadian rhythms (CRs) are intrinsic clocks organizing the behavior and physiology of organisms. These clocks are thought to have coevolved with cellular redox regulation. Metabolism, redox homeostasis, circadian clock, and diet offer insights into aging. Mitochondria play a pivotal role in redox homeostasis, CR, and aging. Melatonin is synthesized in mitochondria, is the key regulator of CRs, and shows substantial antioxidative effects. Melatonin levels tend to decrease significantly with advancing age. Recent reports showed that disruptions of CRs may render aging populations even more susceptible to age-related disorders. Recent and high-quality articles investigating CR, redox homeostasis, aging, and their relationship during aging process were included. Putting special emphasis on the possible effects of melatonin on redox homeostasis and mitochondrial dynamics, recent clinical evidence highlighting the importance of circadian mechanisms was utilized. A deeper understanding of the role of altered mitochondrial redox homeostasis in the pathogenesis of age-related disorders and its relationship with CR could offer novel therapeutic interventions. Chronotherapy, a therapeutic approach considering CR of organisms and best therapeutic times, could potentially reduce side effects and improve therapeutic efficiency. Redox homeostasis, energy metabolism, and CR are all intertwined.

摘要

昼夜节律(CRs)是组织生物体行为和生理的内在时钟。这些时钟被认为是与细胞氧化还原调节共同进化的。代谢、氧化还原稳态、昼夜节律钟和饮食为衰老提供了见解。线粒体在氧化还原稳态、昼夜节律和衰老中起关键作用。褪黑素在线粒体中合成,是昼夜节律的关键调节因子,并具有显著的抗氧化作用。褪黑素水平往往会随着年龄的增长而显著下降。最近的报告表明,昼夜节律的紊乱可能使老年人群更容易患与年龄相关的疾病。本文纳入了近期高质量的文章,这些文章研究了昼夜节律、氧化还原稳态、衰老以及它们在衰老过程中的关系。特别强调了褪黑素对氧化还原稳态和线粒体动力学的可能影响,并利用了近期突出昼夜节律机制重要性的临床证据。更深入地了解线粒体氧化还原稳态改变在与年龄相关疾病发病机制中的作用及其与昼夜节律的关系,可能会提供新的治疗干预措施。时间治疗法是一种考虑生物体昼夜节律和最佳治疗时间的治疗方法,有可能减少副作用并提高治疗效率。氧化还原稳态、能量代谢和昼夜节律都是相互交织的。

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