CaMKII oxidation is a critical performance/disease trade-off acquired at the dawn of vertebrate evolution
Year: 2021
Type: article
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.
Source: Nature Communications
Authors: Qinchuan Wang, Erick O. Hernández-Ochoa, Meera C. Viswanathan, Ian D. Blum, Danh C. Do, Jonathan M. Granger, Kevin R. Murphy, An-Chi Wei, Susan Aja, Naili Liu, Corina M. Antonescu, Liliana D. Florea, C. Conover Talbot, David Mohr, Kathryn R. Wagner, Sergi Regot, Richard M. Lovering, Peisong Gao, Mario A. Bianchet, Mark N. Wu, Anthony Cammarato, Martin F. Schneider, Gabriel S. Bever, Mark E. Anderson
Language: English
Subfield: Aging
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,560
Funders: U.S. Department of Health and Human Services, Johns Hopkins University, National Institutes of Health, National Heart, Lung, and Blood Institute, National Institute of General Medical Sciences, National Institute of Neurological Disorders and Stroke, National Institute of Arthritis and Musculoskeletal and Skin Diseases
Awards: G1088858851, G1200870472, G1299016871, Roles of voltage sensor, S100A1 and calmodulin in skeletal muscle Ca2+ signaling, CaMKII signaling in physiology, heart failure and arrhythmias, Mechanisms of Force Loss in Injured and Dystrophic Skeletal Muscle, G3383206953, G4758838356, G484151221, G4943657301, G5763893963, G626253955, G6390838128, G7279053853, G9000194750, G9000234996, G9000269850, Voltage sensor domain movements in skeletal muscle fiber activation, PATHOGENESIS AND IN VIVO SUPPRESSION OF THIN FILAMENT-BASED CARDIOMYOPATHIES
OpenAlex ID: W3165287397