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dc.contributor.authorGarcía-Casas, Paloma
dc.contributor.authorAlvarez-Illera, Pilar
dc.contributor.authorGómez-Orte, Eva
dc.contributor.authorCabello, Juan
dc.contributor.authorFonteriz, Rosalba I.
dc.contributor.authorMontero Zoccola, María Teresa 
dc.contributor.authorÁlvarez Martín, Javier 
dc.date.accessioned2024-02-09T12:03:18Z
dc.date.available2024-02-09T12:03:18Z
dc.date.issued2021
dc.identifier.citationFrontiers in Pharmacology, Junio 2021, 12, 695687es
dc.identifier.issn1663-9812es
dc.identifier.urihttps://uvadoc.uva.es/handle/10324/66082
dc.descriptionProducción Científicaes
dc.description.abstractWe have reported recently that the mitochondrial Na+/Ca2+ exchanger inhibitor CGP37157 extends lifespan in Caenorhabditis elegans by a mechanism involving mitochondria, the TOR pathway and the insulin/IGF1 pathway. Here we show that CGP37157 significantly improved the evolution with age of the sarcomeric regular structure, delaying development of sarcopenia in C. elegans body wall muscle and increasing the average and maximum speed of the worms. Similarly, CGP37157 favored the maintenance of a regular mitochondrial structure during aging. We have also investigated further the mechanism of the effect of CGP37157 by studying its effect in mutants of aak-1;aak-2/AMP-activated kinase, sir-2.1/sirtuin, rsks-1/S6 kinase and daf-16/FOXO. We found that this compound was still effective increasing lifespan in all these mutants, indicating that these pathways are not involved in the effect. We have then monitored pharynx cytosolic and mitochondrial Ca2+ signalling and our results suggest that CGP37157 is probably inhibiting not only the mitochondrial Na+/Ca2+ exchanger, but also Ca2+ entry through the plasma membrane. Finally, a transcriptomic study detected that CGP37157 induced changes in lipid metabolism enzymes and a four-fold increase in the expression of ncx-6, one of the C. elegans mitochondrial Na+/Ca2+ exchangers. In summary, CGP37157 increases both lifespan and healthspan by a mechanism involving changes in cytosolic and mitochondrial Ca2+ homeostasis. Thus, Ca2+ signalling could be a promising target to act on aging.es
dc.format.mimetypeapplication/pdfes
dc.language.isoenges
dc.publisherFrontierses
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subject.classificationC. elegans, CGP37157, lifespan, endoplasmic reticulum, mitochondria, sarcopeniaes
dc.titleThe Mitochondrial Na+/Ca2+ Exchanger Inhibitor CGP37157 Preserves Muscle Structure and Function to Increase Lifespan and Healthspan in Caenorhabditis eleganses
dc.typeinfo:eu-repo/semantics/articlees
dc.identifier.doi10.3389/fphar.2021.695687es
dc.relation.publisherversionhttps://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.695687/fulles
dc.identifier.publicationtitleFrontiers in Pharmacologyes
dc.identifier.publicationvolume12es
dc.peerreviewedSIes
dc.description.projectMICINN project BFU2017-83509-Res
dc.description.projectMICINN project PGC 2018–094276-B-I00es
dc.identifier.essn1663-9812es
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersiones


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