The mitochondrial Na+/Ca2+ exchanger inhibitor CGP37157 preserves muscle structure and function to increase lifespan and healthspan in caenorhabditis elegans

© 2021 García-Casas, Alvarez-Illera, Gómez-Orte, Cabello, Fonteriz, Montero and Alvarez.

Detalles Bibliográficos
Autores: García-Casas, Paloma, Alvarez-Illera, Pilar, Gómez-Orte, Eva, Cabello, Juan, Fonteriz, Rosalba I., Montero, Mayte, Álvarez, Javier
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/260891
Acceso en línea:http://hdl.handle.net/10261/260891
Access Level:acceso abierto
Palabra clave:C. elegans
CGP37157
Lifespan
Endoplasmic reticulum
Mitochondria
Sarcopenia
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spelling The mitochondrial Na+/Ca2+ exchanger inhibitor CGP37157 preserves muscle structure and function to increase lifespan and healthspan in caenorhabditis elegansGarcía-Casas, PalomaAlvarez-Illera, PilarGómez-Orte, EvaCabello, JuanFonteriz, Rosalba I.Montero, MayteÁlvarez, JavierC. elegansCGP37157LifespanEndoplasmic reticulumMitochondriaSarcopenia© 2021 García-Casas, Alvarez-Illera, Gómez-Orte, Cabello, Fonteriz, Montero and Alvarez.We 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.This work was supported by a grant from the Spanish Ministerio de Economía, Industria y Competitividad (BFU2017-83509-R) to JA and MM, project co-financed by the European Union through the European Regional Development Fund, and by grants from the Spanish Ministerio de Ciencia, Innovación y Universidades (PGC 2018–094276-B-I00) and the Rioja Salud Foundation (FEDER funds) to JC. PG-C had a FPI fellowship from Ministerio de Economía y Competitividad. Financial support from Programa Estratégico Instituto de Biología y Genética Molecular (IBGM), Escalera de Excelencia, Junta de Castilla y León (Ref. CLU-2019-02) is gratefully acknowledged. Some C. elegans strains were provided by the Caenorhabditis Genetics Center (CGC), which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440).Frontiers MediaAgencia Estatal de Investigación (España)Ministerio de Ciencia, Innovación y Universidades (España)Fundación Rioja SaludMinisterio de Economía y Competitividad (España)CSIC-UVA - Instituto de Biología y Genética Molecular (IBGM)Junta de Castilla y LeónNational Institutes of Health (US)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2022202220212022info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/260891reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BFU2017-83509-Rinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PGC2018-094276-B-I00http://dx.doi.org/10.3389/fphar.2021.695687Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2608912026-05-22T06:33:51Z
dc.title.none.fl_str_mv The mitochondrial Na+/Ca2+ exchanger inhibitor CGP37157 preserves muscle structure and function to increase lifespan and healthspan in caenorhabditis elegans
title The mitochondrial Na+/Ca2+ exchanger inhibitor CGP37157 preserves muscle structure and function to increase lifespan and healthspan in caenorhabditis elegans
spellingShingle The mitochondrial Na+/Ca2+ exchanger inhibitor CGP37157 preserves muscle structure and function to increase lifespan and healthspan in caenorhabditis elegans
García-Casas, Paloma
C. elegans
CGP37157
Lifespan
Endoplasmic reticulum
Mitochondria
Sarcopenia
title_short The mitochondrial Na+/Ca2+ exchanger inhibitor CGP37157 preserves muscle structure and function to increase lifespan and healthspan in caenorhabditis elegans
title_full The mitochondrial Na+/Ca2+ exchanger inhibitor CGP37157 preserves muscle structure and function to increase lifespan and healthspan in caenorhabditis elegans
title_fullStr The mitochondrial Na+/Ca2+ exchanger inhibitor CGP37157 preserves muscle structure and function to increase lifespan and healthspan in caenorhabditis elegans
title_full_unstemmed The mitochondrial Na+/Ca2+ exchanger inhibitor CGP37157 preserves muscle structure and function to increase lifespan and healthspan in caenorhabditis elegans
title_sort The mitochondrial Na+/Ca2+ exchanger inhibitor CGP37157 preserves muscle structure and function to increase lifespan and healthspan in caenorhabditis elegans
dc.creator.none.fl_str_mv García-Casas, Paloma
Alvarez-Illera, Pilar
Gómez-Orte, Eva
Cabello, Juan
Fonteriz, Rosalba I.
Montero, Mayte
Álvarez, Javier
author García-Casas, Paloma
author_facet García-Casas, Paloma
Alvarez-Illera, Pilar
Gómez-Orte, Eva
Cabello, Juan
Fonteriz, Rosalba I.
Montero, Mayte
Álvarez, Javier
author_role author
author2 Alvarez-Illera, Pilar
Gómez-Orte, Eva
Cabello, Juan
Fonteriz, Rosalba I.
Montero, Mayte
Álvarez, Javier
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Agencia Estatal de Investigación (España)
Ministerio de Ciencia, Innovación y Universidades (España)
Fundación Rioja Salud
Ministerio de Economía y Competitividad (España)
CSIC-UVA - Instituto de Biología y Genética Molecular (IBGM)
Junta de Castilla y León
National Institutes of Health (US)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv C. elegans
CGP37157
Lifespan
Endoplasmic reticulum
Mitochondria
Sarcopenia
topic C. elegans
CGP37157
Lifespan
Endoplasmic reticulum
Mitochondria
Sarcopenia
description © 2021 García-Casas, Alvarez-Illera, Gómez-Orte, Cabello, Fonteriz, Montero and Alvarez.
publishDate 2021
dc.date.none.fl_str_mv 2021
2022
2022
2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/260891
url http://hdl.handle.net/10261/260891
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BFU2017-83509-R
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PGC2018-094276-B-I00
http://dx.doi.org/10.3389/fphar.2021.695687
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
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