@article{146c8a0804b848e58d578afa270ab404,
title = "CaMKII oxidation is a critical performance/disease trade-off acquired at the dawn of vertebrate evolution",
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 Ca2+ 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.",
author = "Qinchuan Wang and Hern{\'a}ndez-Ochoa, {Erick O.} and Viswanathan, {Meera C.} and Blum, {Ian D.} and Do, {Danh C.} and Granger, {Jonathan M.} and Murphy, {Kevin R.} and Wei, {An Chi} and Susan Aja and Naili Liu and Antonescu, {Corina M.} and Florea, {Liliana D.} and Talbot, {C. Conover} and David Mohr and Wagner, {Kathryn R.} and Sergi Regot and Lovering, {Richard M.} and Peisong Gao and Bianchet, {Mario A.} and Wu, {Mark N.} and Anthony Cammarato and Schneider, {Martin F.} and Bever, {Gabriel S.} and Anderson, {Mark E.}",
note = "Funding Information: We thank Drs. Hal Dietz and Gregg Semenza for their insightful comments and suggestions, Dr. Andrew Feinberg for sharing instruments, Teresa Ruggle for assistance in graphic design, Benjamin Garlow for assistance in developing KTR, Jinying Yang for managing mice, Tran Nguyen for maintaining fly stocks, Dr. G. William Wang for technical help in insulin sensitivity and glucose tolerance tests. This work was supported by the National Institutes of Health (R35-HL140034 to M.E.A., R37-AR055099 to E.O.H. and M.F.S., R01-AR059179 and R21-AR067872-01 to R.M.L., R01-HL124091 to M.C.V. and A.C., R01-NS079584 to M.N.W., R21-NS108842 to M.A.B.) and by the Michel Mirowski Discovery award at Johns Hopkins University to M.A.B. Publisher Copyright: {\textcopyright} 2021, The Author(s).",
year = "2021",
month = dec,
day = "1",
doi = "10.1038/s41467-021-23549-3",
language = "English (US)",
volume = "12",
journal = "Nature communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}