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

Producción Científica

Detalhes bibliográficos
Autores: García Casas, Paloma, Álvarez Illera, María Pilar, Gómez Orte, Eva, Cabello, Juan, Fonteriz García, Rosalba Inés, Montero Zoccola, María Teresa, Álvarez Martín, Javier
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2021
País:España
Recursos:Universidad de Valladolid
Repositório:UVaDOC. Repositorio Documental de la Universidad de Valladolid
OAI Identifier:oai:uvadoc.uva.es:10324/66082
Acesso em linha:https://doi.org/10.3389/fphar.2021.695687
https://uvadoc.uva.es/handle/10324/66082
Access Level:Acceso aberto
Palavra-chave:C. elegans
CGP37157
lifespan
endoplasmic reticulum
mitochondria
sarcopenia
2415 Biología Molecular
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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, PalomaÁlvarez Illera, María PilarGómez Orte, EvaCabello, JuanFonteriz García, Rosalba InésMontero Zoccola, María TeresaÁlvarez Martín, JavierC. elegansCGP37157lifespanendoplasmic reticulummitochondriasarcopenia2415 Biología MolecularProducción CientíficaWe 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.MICINN project BFU2017-83509-RMICINN project PGC 2018–094276-B-I00Frontiers2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://doi.org/10.3389/fphar.2021.695687https://uvadoc.uva.es/handle/10324/66082reponame:UVaDOC. Repositorio Documental de la Universidad de Valladolidinstname:Universidad de ValladolidIngléshttps://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.695687/fullinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/4.0/oai:uvadoc.uva.es:10324/660822026-06-13T12:44:47Z
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
2415 Biología Molecular
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
Álvarez Illera, María Pilar
Gómez Orte, Eva
Cabello, Juan
Fonteriz García, Rosalba Inés
Montero Zoccola, María Teresa
Álvarez Martín, Javier
author García Casas, Paloma
author_facet García Casas, Paloma
Álvarez Illera, María Pilar
Gómez Orte, Eva
Cabello, Juan
Fonteriz García, Rosalba Inés
Montero Zoccola, María Teresa
Álvarez Martín, Javier
author_role author
author2 Álvarez Illera, María Pilar
Gómez Orte, Eva
Cabello, Juan
Fonteriz García, Rosalba Inés
Montero Zoccola, María Teresa
Álvarez Martín, Javier
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv C. elegans
CGP37157
lifespan
endoplasmic reticulum
mitochondria
sarcopenia
2415 Biología Molecular
topic C. elegans
CGP37157
lifespan
endoplasmic reticulum
mitochondria
sarcopenia
2415 Biología Molecular
description Producción Científica
publishDate 2021
dc.date.none.fl_str_mv 2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://doi.org/10.3389/fphar.2021.695687
https://uvadoc.uva.es/handle/10324/66082
url https://doi.org/10.3389/fphar.2021.695687
https://uvadoc.uva.es/handle/10324/66082
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.695687/full
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/4.0/
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Frontiers
publisher.none.fl_str_mv Frontiers
dc.source.none.fl_str_mv reponame:UVaDOC. Repositorio Documental de la Universidad de Valladolid
instname:Universidad de Valladolid
instname_str Universidad de Valladolid
reponame_str UVaDOC. Repositorio Documental de la Universidad de Valladolid
collection UVaDOC. Repositorio Documental de la Universidad de Valladolid
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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