Demands of an aging mechanism theory

Y. Tozawa

Department of Nephrology and Endocrinology, University Hospital, Department of Molecular Preventive Medicine, School of Medicine, University of Tokyo, Japan; Division of Applied Life Sciences, Kyoto University, Kitashirakawa, Sakyo-ku, Kyoto, Japan

The endogenous quinonoid indole-2,3-dione, which has a bright orange color because it absorbs blue light, undergoes circadian control and has long been identified among plants and bacteria to be produced by metabolic pathways that are catalyzed by enzymes and are lost in animals. Here, I report the age-associated increase in indole-2,3-dione, which interferes with ATP or NAD(P)H binding to atrial natriuretic peptide receptors, peripheral benzodiazepine receptors and blue light receptor flavoenzymes. Indole-2,3-dione has dual reactivity towards glutathione (GSH)/proteins and DNA/RNA as both a hard and soft electrophile, and its formation rate depends on tyrosine hydroxylase activity and may affect the cell fate, GSH status, NAD(P)+-linked oxidation, functions of cytochromes and ADP/ATP-linked energy conservation, at least through caspase 3 inhibition or carbon monoxide liberation.

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