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

dc.contributor.authorPamplona Gras, Reinald
dc.contributor.authorPortero Otín, Manuel
dc.contributor.authorNaudí i Farré, Alba
dc.contributor.authorFuente, Monica de la
dc.contributor.authorBarja, Gustavo
dc.contributor.authorLópez Torres, Mónica
dc.contributor.authorMate, Ianire
dc.contributor.authorCruces, Julia
dc.contributor.authorGómez, José
dc.contributor.authorSánchez-Roman, Ines
dc.contributor.authorGómez Rodríguez, Alexia
dc.date.accessioned2015-11-16T10:55:40Z
dc.date.available2015-11-16T10:55:40Z
dc.date.issued2014
dc.description.abstractThe membrane fatty acid unsaturation hypothesis of aging and longevity is experimentally tested for the first time in mammals. Lifelong treatment of mice with the b1-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. Weconclude that it is atenolol that failed to increase longevity, and likely not the decrease in membrane unsaturation induced by the drug.ca_ES
dc.description.sponsorshipThis investigation was supported by I + D grants from the Spanish Ministry of Science and Innovation (BFU2011-23888 to G.Barja); UCMGroups of Research (910379ENEROINN), BFU2011-30336, and RETICEF (RD 12/0043/0018) from ISCIII-FEDER of the European Union to M. De la Fuente; Spanish Ministry of Health (PI11/01532) to M.Portero Otin; and Spanish Ministry of Science and Innovation (BFU2009-11879) and the Generalitat of Catalonia (2009SGR735) to R. Pamplona.
dc.identifier.doihttps://doi.org/10.1111/acel.12205
dc.identifier.idgrec021860
dc.identifier.issn1474-9718
dc.identifier.urihttp://hdl.handle.net/10459.1/48966
dc.language.isoengca_ES
dc.publisherWiley Open Accessca_ES
dc.publisherAnatomical Society of Great Britain and Irelandca_ES
dc.relationinfo:eu-repo/grantAgreement/MICINN//BFU2011-23888/ES/EFECTOS Y MECANISMOS DE ACCION DEL FARMACO BETA1-BLOQUEANTE ATENOLOL Y DE LA RESTRICCION DE METIONINA EN LA DIETA SOBRE EL ESTRES OXIDATIVO EN RELACION CON LA LONGEVIDAD/
dc.relationinfo:eu-repo/grantAgreement/MICINN//BFU2011-30336/ES/MODELOS DE ENVEJECIMIENTO PREMATURO EN RATONES. MECANISMOS INMUNITARIOS IMPLICADOS Y ESTRATEGIAS PARA AUMENTAR LA LONGEVIDAD/
dc.relationinfo:eu-repo/grantAgreement/MICINN//PI11%2F01532/ES/Mecanismos de senescencia celular basados en estrés oxidativo en la patogenia de la esclerosis lateral amiotrófica/
dc.relationinfo:eu-repo/grantAgreement/MICINN//BFU2009-11879/ES/Efecto Del Envejecimiento Y De La Restriccion De Metionina Sobre La Vulnerabilidad Neuronal Al Estres Oxidativo En Diferentes Regiones Del Sistema Nervioso Central/
dc.relation.isformatofReproducció del document publicat a https://doi.org/10.1111/acel.12205ca_ES
dc.relation.ispartofAging Cell, 2014, vol. 13, p. 551-560ca_ES
dc.rightscc-by (c) Gómez, Alexia et al., 2012ca_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccessca_ES
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/es/*
dc.subjectAgingca_ES
dc.subjectAtenololca_ES
dc.subjectFatty acid unsaturationca_ES
dc.titleLifelong treatment with atenolol decreases membrane fatty acid unsaturation and oxidative stress in heart and skeletal muscle mitochondria and improves immunity and behaviour, without changing mice longevity.ca_ES
dc.typearticleca_ES
dc.type.versionpublishedVersionca_ES
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