Journal article
Lipid hydroperoxides promote sarcopenia through carbonyl stress
eLife, Vol.12, e85289
03/23/2023
DOI: 10.7554/eLife.85289
PMCID: PMC10076018
PMID: 36951533
Abstract
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 mediates 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.
Details
- Title: Subtitle
- Lipid hydroperoxides promote sarcopenia through carbonyl stress
- Creators
- Hiroaki Eshima - University of UtahJustin L Shahtout - University of UtahPiyarat Siripoksup - University of UtahMacKenzie J Pearson - Sciex (Canada)Ziad S Mahmassani - University of UtahPatrick J Ferrara - University of UtahAlexis W Lyons - University of UtahJohn Alan Maschek - University of UtahAlek D Peterlin - University of UtahAnthony R P Verkerke - University of UtahJordan M Johnson - University of UtahAnahy Salcedo - University of UtahJonathan J Petrocelli - University of UtahEdwin R Miranda - University of UtahEthan J Anderson - University of IowaSihem Boudina - University of UtahQitao Ran - The University of Texas Health Science Center at San AntonioJames E Cox - University of UtahMicah J Drummond - University of UtahKatsuhiko Funai - University of Utah
- Resource Type
- Journal article
- Publication Details
- eLife, Vol.12, e85289
- DOI
- 10.7554/eLife.85289
- PMID
- 36951533
- PMCID
- PMC10076018
- NLM abbreviation
- Elife
- ISSN
- 2050-084X
- eISSN
- 2050-084X
- Grant note
- AG074535 / NIH HHS 915674 / American Heart Association AG050781 / NIH HHS HL149870 / NIH HHS Predoctoral fellowship / Larry H. & Gail Miller Family Foundation AG057006 / NIH HHS GM144613 / NIH HHS HL139451 / NIH HHS AG063077 / NIH HHS Postdoctoral fellowship / Uehara Memorial Foundation AG073493 / NIH HHS 18PRE33960491 / American Heart Association HL122863 / NIH HHS 19PRE34380991 / American Heart Association AG064078 / NIH HHS R01 AG074535 / NIA NIH HHS DK130555 / NIH HHS DK107397 / NIH HHS R01 AG050781 / NIA NIH HHS DK127979 / NIH HHS
- Language
- English
- Date published
- 03/23/2023
- Academic Unit
- Pharmaceutical Sciences and Experimental Therapeutics; Fraternal Order of Eagles Diabetes Research Center; Health, Sport, and Human Physiology
- Record Identifier
- 9984380371002771
Metrics
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