5-Methoxyindole-2-Carboxylic acid (MICA) as a potential caloric restriction mimetic

Purpose: Calorie restriction (CR), as an intervention to influence aging and disease, has been demonstrated to show an inhibitory effect on dihydrolipoamide dehydrogenase (DLD), the E3 subunit of pyruvate dehydrogenase. Elevated DLD activity has been linked with an increased generation of reactive oxygen species (ROS). Increased levels of ROS contribute to aging effects and decreased life span. Theoretically, an inhibitor of DLD would produce the same decrease in ROS as CR. Methods: Searching PubMed with keywords such as caloric restriction, dihydrolipoamide dehydrogenase, 5-methoxyindole-2-carboxylic acid, reactive oxygen species, etc. Results: 5-Methoxyindole-2-Carboxylic acid (MICA) has been shown to inhibit DLD activity which could potentially limit the level of ROS produced in the body. Conclusion: Because of this mechanism of action, we have proposed that MICA has the potential to provide, at least in part, calorie restrictive mimicry by carrying out some of the beneficial physiological effects of CR.