T cells with dysfunctional mitochondria induce multimorbidity and premature senescence.

The effect of immunometabolism on age-associated diseases remains uncertain. In this work, we show that T cells with dysfunctional mitochondria owing to mitochondrial transcription factor A (TFAM) deficiency act as accelerators of senescence. In mice, these cells instigate multiple aging-related fea...

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Detalhes bibliográficos
Autores: Desdín-Micó, Gabriela, Soto-Heredero, Gonzalo, Aranda, Juan Francisco, Oller, Jorge, Carrasco, Elisa, Gabandé-Rodríguez, Enrique, Blanco, Eva Maria, Alfranca, Arantzazu, Cusso, Lorena, Desco, Manuel, Ibáñez, Borja, Gortazar, Arancha R, Fernández-Marcos, Pablo, Navarro, Maria N, Hernaez, Bruno, Alcamí, Antonio, Baixauli, Francesc, Mittelbrunn, María
Tipo de documento: artigo
Data de publicação:2020
País:España
Recursos:Instituto de Salud Carlos III (ISCIII)
Repositório:Repisalud
Idioma:inglês
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/10721
Acesso em linha:http://hdl.handle.net/20.500.12105/10721
Access Level:Acceso aberto
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spelling T cells with dysfunctional mitochondria induce multimorbidity and premature senescence.Desdín-Micó, GabrielaSoto-Heredero, GonzaloAranda, Juan FranciscoOller, JorgeCarrasco, ElisaGabandé-Rodríguez, EnriqueBlanco, Eva MariaAlfranca, ArantzazuCusso, LorenaDesco, ManuelIbáñez, BorjaGortazar, Arancha RFernández-Marcos, PabloNavarro, Maria NHernaez, BrunoAlcamí, AntonioBaixauli, FrancescMittelbrunn, MaríaThe effect of immunometabolism on age-associated diseases remains uncertain. In this work, we show that T cells with dysfunctional mitochondria owing to mitochondrial transcription factor A (TFAM) deficiency act as accelerators of senescence. In mice, these cells instigate multiple aging-related features, including metabolic, cognitive, physical, and cardiovascular alterations, which together result in premature death. T cell metabolic failure induces the accumulation of circulating cytokines, which resembles the chronic inflammation that is characteristic of aging ("inflammaging"). This cytokine storm itself acts as a systemic inducer of senescence. Blocking tumor necrosis factor-α signaling or preventing senescence with nicotinamide adenine dinucleotide precursors partially rescues premature aging in mice with Tfam-deficient T cells. Thus, T cells can regulate organismal fitness and life span, which highlights the importance of tight immunometabolic control in both aging and the onset of age-associated diseases.American Association for the Advancement of Science (AAAS)Instituto de Salud Carlos IIIUnión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)Unión Europea. Comisión EuropeaUnión Europea. Comisión Europea. European Research Council (ERC)Comunidad de Madrid (España)Autonomous University of Madrid (España)20202020-07-0820202020-06-0120202020-06-01journal articlehttp://purl.org/coar/resource_type/c_6501AMhttp://purl.org/coar/version/c_ab4af688f83e57aainfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/20.500.12105/10721reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)InglésengES PI16 188ES PI19 855ES PI16 02110European Commission http://dx.doi.org/10.13039/501100000780 Horizon 2020 Framework Programme 715322European Commission http://dx.doi.org/10.13039/501100000780 Horizon 2020 Framework Programme 819775open accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/107212026-06-12T12:43:37Z
dc.title.none.fl_str_mv T cells with dysfunctional mitochondria induce multimorbidity and premature senescence.
title T cells with dysfunctional mitochondria induce multimorbidity and premature senescence.
spellingShingle T cells with dysfunctional mitochondria induce multimorbidity and premature senescence.
Desdín-Micó, Gabriela
title_short T cells with dysfunctional mitochondria induce multimorbidity and premature senescence.
title_full T cells with dysfunctional mitochondria induce multimorbidity and premature senescence.
title_fullStr T cells with dysfunctional mitochondria induce multimorbidity and premature senescence.
title_full_unstemmed T cells with dysfunctional mitochondria induce multimorbidity and premature senescence.
title_sort T cells with dysfunctional mitochondria induce multimorbidity and premature senescence.
dc.creator.none.fl_str_mv Desdín-Micó, Gabriela
Soto-Heredero, Gonzalo
Aranda, Juan Francisco
Oller, Jorge
Carrasco, Elisa
Gabandé-Rodríguez, Enrique
Blanco, Eva Maria
Alfranca, Arantzazu
Cusso, Lorena
Desco, Manuel
Ibáñez, Borja
Gortazar, Arancha R
Fernández-Marcos, Pablo
Navarro, Maria N
Hernaez, Bruno
Alcamí, Antonio
Baixauli, Francesc
Mittelbrunn, María
author Desdín-Micó, Gabriela
author_facet Desdín-Micó, Gabriela
Soto-Heredero, Gonzalo
Aranda, Juan Francisco
Oller, Jorge
Carrasco, Elisa
Gabandé-Rodríguez, Enrique
Blanco, Eva Maria
Alfranca, Arantzazu
Cusso, Lorena
Desco, Manuel
Ibáñez, Borja
Gortazar, Arancha R
Fernández-Marcos, Pablo
Navarro, Maria N
Hernaez, Bruno
Alcamí, Antonio
Baixauli, Francesc
Mittelbrunn, María
author_role author
author2 Soto-Heredero, Gonzalo
Aranda, Juan Francisco
Oller, Jorge
Carrasco, Elisa
Gabandé-Rodríguez, Enrique
Blanco, Eva Maria
Alfranca, Arantzazu
Cusso, Lorena
Desco, Manuel
Ibáñez, Borja
Gortazar, Arancha R
Fernández-Marcos, Pablo
Navarro, Maria N
Hernaez, Bruno
Alcamí, Antonio
Baixauli, Francesc
Mittelbrunn, María
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Instituto de Salud Carlos III
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
Unión Europea. Comisión Europea
Unión Europea. Comisión Europea. European Research Council (ERC)
Comunidad de Madrid (España)
Autonomous University of Madrid (España)
description The effect of immunometabolism on age-associated diseases remains uncertain. In this work, we show that T cells with dysfunctional mitochondria owing to mitochondrial transcription factor A (TFAM) deficiency act as accelerators of senescence. In mice, these cells instigate multiple aging-related features, including metabolic, cognitive, physical, and cardiovascular alterations, which together result in premature death. T cell metabolic failure induces the accumulation of circulating cytokines, which resembles the chronic inflammation that is characteristic of aging ("inflammaging"). This cytokine storm itself acts as a systemic inducer of senescence. Blocking tumor necrosis factor-α signaling or preventing senescence with nicotinamide adenine dinucleotide precursors partially rescues premature aging in mice with Tfam-deficient T cells. Thus, T cells can regulate organismal fitness and life span, which highlights the importance of tight immunometabolic control in both aging and the onset of age-associated diseases.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020-07-08
2020
2020-06-01
2020
2020-06-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
AM
http://purl.org/coar/version/c_ab4af688f83e57aa
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12105/10721
url http://hdl.handle.net/20.500.12105/10721
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv ES PI16 188
ES PI19 855
ES PI16 02110
European Commission http://dx.doi.org/10.13039/501100000780 Horizon 2020 Framework Programme 715322
European Commission http://dx.doi.org/10.13039/501100000780 Horizon 2020 Framework Programme 819775
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv American Association for the Advancement of Science (AAAS)
publisher.none.fl_str_mv American Association for the Advancement of Science (AAAS)
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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