Lifelong treatment with atenolol decreases membrane fatty acid unsaturation and oxidative stress in heart and skeletal muscle mitochondria and improves immunity and behavior, without changing mice longevity

Authors

  • Alexia Gómez,

    1. Department of Animal Physiology-II, Faculty of Biological Sciences, Complutense University of Madrid (UCM), Madrid, Spain
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  • Ines Sánchez-Roman,

    1. Department of Animal Physiology-II, Faculty of Biological Sciences, Complutense University of Madrid (UCM), Madrid, Spain
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  • Jose Gomez,

    1. Department of Animal Physiology-II, Faculty of Biological Sciences, Complutense University of Madrid (UCM), Madrid, Spain
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  • Julia Cruces,

    1. Department of Animal Physiology-II, Faculty of Biological Sciences, Complutense University of Madrid (UCM), Madrid, Spain
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  • Ianire Mate,

    1. Department of Animal Physiology-II, Faculty of Biological Sciences, Complutense University of Madrid (UCM), Madrid, Spain
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  • Mónica Lopez-Torres,

    1. Department of Animal Physiology-II, Faculty of Biological Sciences, Complutense University of Madrid (UCM), Madrid, Spain
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  • Alba Naudi,

    1. Department of Experimental Medicine, Faculty of Medicine, University of Lleida-IRBLLEIDA, Lleida, Spain
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  • Manuel Portero-Otin,

    1. Department of Experimental Medicine, Faculty of Medicine, University of Lleida-IRBLLEIDA, Lleida, Spain
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  • Reinald Pamplona,

    1. Department of Experimental Medicine, Faculty of Medicine, University of Lleida-IRBLLEIDA, Lleida, Spain
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  • Monica De la Fuente,

    1. Department of Animal Physiology-II, Faculty of Biological Sciences, Complutense University of Madrid (UCM), Madrid, Spain
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  • Gustavo Barja

    Corresponding author
    1. Department of Animal Physiology-II, Faculty of Biological Sciences, Complutense University of Madrid (UCM), Madrid, Spain
    • Correspondence

      Dr. Gustavo Barja, Departamento de Fisiología Animal II, Facultad de Ciencias Biológicas, Universidad Complutense, c/ Jose Antonio Novais 2, Madrid 28040, Spain. Tel.: +34 91 3944919; fax: +34 91 3944935; e-mail: gbarja@bio.ucm.es

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Summary

The membrane fatty acid unsaturation hypothesis of aging and longevity is experimentally tested for the first time in mammals. Lifelong treatment of mice with the β1-blocker atenolol increased the amount of the extracellular-signal-regulated kinase signaling protein and successfully decreased one of the two traits appropriately correlating with animal longevity, the membrane fatty acid unsaturation degree of cardiac and skeletal muscle mitochondria, changing their lipid profile toward that present in much more longer-lived mammals. This was mainly due to decreases in 22:6n-3 and increases in 18:1n-9 fatty acids. The atenolol treatment also lowered visceral adiposity (by 24%), decreased mitochondrial protein oxidative, glycoxidative, and lipoxidative damage in both organs, and lowered oxidative damage in heart mitochondrial DNA. Atenolol also improved various immune (chemotaxis and natural killer activities) and behavioral functions (equilibrium, motor coordination, and muscular vigor). It also totally or partially prevented the aging-related detrimental changes observed in mitochondrial membrane unsaturation, protein oxidative modifications, and immune and behavioral functions, without changing longevity. The controls reached 3.93 years of age, a substantially higher maximum longevity than the best previously described for this strain (3.0 years). Side effects of the drug could have masked a likely lowering of the endogenous aging rate induced by the decrease in membrane fatty acid unsaturation. We conclude that it is atenolol that failed to increase longevity, and likely not the decrease in membrane unsaturation induced by the drug.

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