The redox balance of cells provides a stable microenvironment for various biological macromolecules to perform their normal functions. The theory of free radical in aging points out that oxidative stress caused by a large number of free radicals is an important cause of aging. However, redox-based therapeutic strategies have not yet shown satisfactory results. To find the key reason is of great significance.

Prof. CHEN Chang of the Institute of Biophysics (IBP), Chinese Academy of Sciences (CAS) together with her coauthor MENG Jiao, an associate research fellow with the IBP, put forward the concept of precision redox for the first time, and emphasized the precise nature of redox regulation. They proposed the "5R" principle of precision redox in antioxidant intervention -- right species, right place, right time, right level and right target, and pointed out that principle is the key to antioxidant pharmacology.

Researchers elucidated the importance and necessity of precision redox strategies from three aspects: differences in redox status, differences in redox function, and differences in the effects of redox therapy.

First, there are differences in redox levels between species. Redox status is thus regulated precisely in a spatiotemporal manner, and different locations (tissues or cellular organelles) and time periods, including different stages of the cell cycle, circadian rhythms, seasons, different stages of life, external environments, and pathological conditions, should be considered to provide an accurate evaluation. In addition to differences in the redox status of different cells or tissues, at the systems level, there are also differences in redox status between individuals.

Different redox statuses are closely related to cell function. For example, the partial oxidation characteristics of the endoplasmic reticulum are closely related to oxidative protein folding. ROS/RNS(Reactive Oxygen Species/Reactive Nitrogen Species), therefore, exert different functions on different targets by oxidative modification. Redox may have opposite effects at different disease stages, and may even cause reductive stress.

Due to the differences in redox status and function, antioxidants for the treatment of many diseases also have different intervention effects. The antioxidants for specific redox indicators, specific organelle in specific disease stages or individuals tend to obtain better therapeutic effect.

The "5R" principle of precision redox explains the reason why the antioxidant effect was not ideal or even counterproductive in the past. In view of the complexity of redox, the "5R" principle of precision redox should be considered in antioxidant pharmacology rather than applying global nonspecific antioxidant treatments. As these five factors affect each other, it will be necessary to consider all or several factors at the same time to achieve real precision redox-based therapy and allow antioxidants to really play their therapeutic effects.

Precision redox is the key for antioxidant pharmacology, and the daily use of antioxidants as nutritional supplements thus also requires precision and should vary from person to person. Future studies to develop more accurate methods for detecting redox status and accurately evaluating the redox state of different physiological and pathological processes are needed. Antioxidant pharmacology should consider the "5R" principle rather than continuing to apply global nonspecific antioxidant treatments.

Relevant results entitled Precision Redox: The Key for Antioxidant Pharmacology have been published online on Antioxidants & Redox Signaling on Dec 12.

The project was supported by the Protein Machinery and Life Process Regulation Special Project of the National Key Research and Development Program of China, the Strategic Priority Research Program of the Chinese Academy of Sciences (Class B), and the National Natural Science Foundation of China.

The principle of precision redox "5R"

Article link：https://www.liebertpub.com/doi/full/10.1089/ars.2020.8212

Contact: CHEN Chang
Institute of Biophysics, Chinese Academy of Sciences
Beijing 100101, China
Email: changchen@ibp.ac.cn

(Reported by Dr. CHEN Chang's group)