TY - JOUR T1 - Lipid hydroperoxides promote sarcopenia through carbonyl stress JF - bioRxiv DO - 10.1101/2021.12.17.473200 SP - 2021.12.17.473200 AU - Hiroaki Eshima AU - Justin L. Shahtout AU - Piyarat Siripoksup AU - MacKenzie J. Pearson AU - Ziad S. Mahmassani AU - Patrick J. Ferrara AU - Alexis W. Lyons AU - J. Alan Maschek AU - Alek D. Peterlin AU - Anthony R. P. Verkerke AU - Jordan M. Johnson AU - Anahy Salcedo AU - Jonathan J. Petrocelli AU - Edwin R. Miranda AU - Ethan J. Anderson AU - Sihem Boudina AU - Qitao Ran AU - James E. Cox AU - Micah J. Drummond AU - Katsuhiko Funai Y1 - 2022/01/01 UR - http://biorxiv.org/content/early/2022/11/18/2021.12.17.473200.abstract N2 - Reactive oxygen species (ROS) accumulation is a cardinal feature of skeletal muscle atrophy. ROS refers to a collection of radical molecules whose cellular signals are vast, and it is unclear which downstream consequences of ROS are responsible for the loss of muscle mass and strength. Here we show that lipid hydroperoxides (LOOH) are increased with age and disuse, and the accumulation of LOOH by deletion of glutathione peroxidase 4 (GPx4) is sufficient to augment muscle atrophy. LOOH promoted atrophy in a lysosomal-dependent, proteasomal-independent manner. In young and old mice, genetic and pharmacologic neutralization of LOOH or their secondary reactive lipid aldehydes robustly prevented muscle atrophy and weakness, indicating that LOOH-derived carbonyl stress mediate age- and disuse-induced muscle dysfunction. Our findings provide novel insights for the role of LOOH in sarcopenia including a therapeutic implication by pharmacologic suppression.Competing Interest StatementThe authors have declared no competing interest. ER -