151. CaMKII oxidation is a critical performance/disease trade-off acquired at the dawn of vertebrate evolution.
- Author
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Wang Q, Hernández-Ochoa EO, Viswanathan MC, Blum ID, Do DC, Granger JM, Murphy KR, Wei AC, Aja S, Liu N, Antonescu CM, Florea LD, Talbot CC Jr, Mohr D, Wagner KR, Regot S, Lovering RM, Gao P, Bianchet MA, Wu MN, Cammarato A, Schneider MF, Bever GS, and Anderson ME
- Subjects
- Animals, Animals, Genetically Modified, CRISPR-Cas Systems genetics, Calcium Signaling physiology, Calcium-Calmodulin-Dependent Protein Kinase Type 2 genetics, Drosophila Proteins genetics, Drosophila Proteins metabolism, Drosophila melanogaster, Female, Gene Editing, Gene Knock-In Techniques, Male, Mice, Models, Animal, Oxidation-Reduction, Phylogeny, Physical Fitness physiology, Point Mutation, Aging physiology, Biological Evolution, Calcium-Calmodulin-Dependent Protein Kinase Type 2 metabolism, Reactive Oxygen Species metabolism, Vertebrates physiology
- Abstract
Antagonistic pleiotropy is a foundational theory that predicts aging-related diseases are the result of evolved genetic traits conferring advantages early in life. Here we examine CaMKII, a pluripotent signaling molecule that contributes to common aging-related diseases, and find that its activation by reactive oxygen species (ROS) was acquired more than half-a-billion years ago along the vertebrate stem lineage. Functional experiments using genetically engineered mice and flies reveal ancestral vertebrates were poised to benefit from the union of ROS and CaMKII, which conferred physiological advantage by allowing ROS to increase intracellular Ca
2+ and activate transcriptional programs important for exercise and immunity. Enhanced sensitivity to the adverse effects of ROS in diseases and aging is thus a trade-off for positive traits that facilitated the early and continued evolutionary success of vertebrates.- Published
- 2021
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