HDAC11 deficiency regulates age-related muscle decline and sarcopenia

Sarcopenia, defined as the progressive loss of skeletal muscle mass and function associated with ageing, has devastating effects in terms of reducing the quality of life of older people. Muscle ageing is characterised by muscle atrophy and decreased capacity for muscle repair, including a reduction...

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Autores: Odria, Renato, Cardús, Aina, Gomis-Coloma, Clara, Balanyà-Segura, Marta, Mercado-Amarilla, Alexandra, Maestre-Mora, Pau, Poveda-Sabuco, Andrea, Domingo, Joan Carles, Nogales-Gadea, Gisela, Gómez-Sánchez, José A., Hurtado, Erica, Suelves, Mònica
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/413401
Acceso en línea:http://hdl.handle.net/10261/413401
https://api.elsevier.com/content/abstract/scopus_id/105002353776
Access Level:acceso abierto
Palabra clave:Fatty acid oxidation
HDAC11
Muscle atrophy
Omega-6/omega-3 fatty acid ratio
Sarcopenia
Skeletal muscle regeneration
id ES_76bbb4a4f074683e76f4698d9138fccc
oai_identifier_str oai:digital.csic.es:10261/413401
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv HDAC11 deficiency regulates age-related muscle decline and sarcopenia
title HDAC11 deficiency regulates age-related muscle decline and sarcopenia
spellingShingle HDAC11 deficiency regulates age-related muscle decline and sarcopenia
Odria, Renato
Fatty acid oxidation
HDAC11
Muscle atrophy
Omega-6/omega-3 fatty acid ratio
Sarcopenia
Skeletal muscle regeneration
title_short HDAC11 deficiency regulates age-related muscle decline and sarcopenia
title_full HDAC11 deficiency regulates age-related muscle decline and sarcopenia
title_fullStr HDAC11 deficiency regulates age-related muscle decline and sarcopenia
title_full_unstemmed HDAC11 deficiency regulates age-related muscle decline and sarcopenia
title_sort HDAC11 deficiency regulates age-related muscle decline and sarcopenia
dc.creator.none.fl_str_mv Odria, Renato
Cardús, Aina
Gomis-Coloma, Clara
Balanyà-Segura, Marta
Mercado-Amarilla, Alexandra
Maestre-Mora, Pau
Poveda-Sabuco, Andrea
Domingo, Joan Carles
Nogales-Gadea, Gisela
Gómez-Sánchez, José A.
Hurtado, Erica
Suelves, Mònica
author Odria, Renato
author_facet Odria, Renato
Cardús, Aina
Gomis-Coloma, Clara
Balanyà-Segura, Marta
Mercado-Amarilla, Alexandra
Maestre-Mora, Pau
Poveda-Sabuco, Andrea
Domingo, Joan Carles
Nogales-Gadea, Gisela
Gómez-Sánchez, José A.
Hurtado, Erica
Suelves, Mònica
author_role author
author2 Cardús, Aina
Gomis-Coloma, Clara
Balanyà-Segura, Marta
Mercado-Amarilla, Alexandra
Maestre-Mora, Pau
Poveda-Sabuco, Andrea
Domingo, Joan Carles
Nogales-Gadea, Gisela
Gómez-Sánchez, José A.
Hurtado, Erica
Suelves, Mònica
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Conferencia de Rectores de las Universidades Españolas
Consejo Superior de Investigaciones Científicas (España)
Ministerio de Economía y Competitividad (España)
Ministerio de Ciencia, Innovación y Universidades (España)
Agencia Estatal de Investigación (España)
Instituto de Salud Carlos III
Programa Nacional de Becas de Postgrado en el Exterior Don Carlos Antonio López (Paraguay)
Generalitat de Catalunya
Suelves, Mònica [0000-0001-7095-5804]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Fatty acid oxidation
HDAC11
Muscle atrophy
Omega-6/omega-3 fatty acid ratio
Sarcopenia
Skeletal muscle regeneration
topic Fatty acid oxidation
HDAC11
Muscle atrophy
Omega-6/omega-3 fatty acid ratio
Sarcopenia
Skeletal muscle regeneration
description Sarcopenia, defined as the progressive loss of skeletal muscle mass and function associated with ageing, has devastating effects in terms of reducing the quality of life of older people. Muscle ageing is characterised by muscle atrophy and decreased capacity for muscle repair, including a reduction in the muscle stem cell pool that impedes recovery after injury. Histone deacetylase 11 (HDAC11) is the newest member of the HDAC family and it is highly expressed in skeletal muscle. Our group recently showed that genetic deficiency in HDAC11 increases skeletal muscle regeneration, mitochondrial function and globally improves muscle performance in young mice. Here, we explore for the first time the functional consequences of HDAC11 deficiency in old mice, in homeostasis and during muscle regeneration. Aged mice lacking HDAC11 show attenuated muscle atrophy and postsynaptic fragmentation of the neuromuscular junction, but no significant differences in the number or diameter of myelinated axons of peripheral nerves. Maintenance of the muscle stem cell reservoir and advanced skeletal muscle regeneration after injury are also observed. HDAC11 depletion enhances mitochondrial fatty acid oxidation and attenuates age-associated alterations in skeletal muscle fatty acid composition, reducing drastically the omega-6/omega-3 fatty acid ratio and improving significantly the omega-3 index, providing an explanation for improved muscle strength and fatigue resistance and decreased mortality. Taken together, our results point to HDAC11 as a new target for the treatment of sarcopenia. Importantly, selective HDAC11 inhibitors have recently been developed that could offer a new therapeutic approach to slow the ageing process.
publishDate 2025
dc.date.none.fl_str_mv 2025
2026
2026
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/10261/413401
https://api.elsevier.com/content/abstract/scopus_id/105002353776
url http://hdl.handle.net/10261/413401
https://api.elsevier.com/content/abstract/scopus_id/105002353776
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
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info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2022-143269OB-I00
info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica, Técnica y de Innovación 2021-2023/PI22%2F00104
The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI 10.1007/s11357-025-01611-y
https://doi.org/10.1007/s11357-025-01611-y
Sí
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dc.publisher.none.fl_str_mv Springer Nature
publisher.none.fl_str_mv Springer Nature
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
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spelling HDAC11 deficiency regulates age-related muscle decline and sarcopeniaOdria, RenatoCardús, AinaGomis-Coloma, ClaraBalanyà-Segura, MartaMercado-Amarilla, AlexandraMaestre-Mora, PauPoveda-Sabuco, AndreaDomingo, Joan CarlesNogales-Gadea, GiselaGómez-Sánchez, José A.Hurtado, EricaSuelves, MònicaFatty acid oxidationHDAC11Muscle atrophyOmega-6/omega-3 fatty acid ratioSarcopeniaSkeletal muscle regenerationSarcopenia, defined as the progressive loss of skeletal muscle mass and function associated with ageing, has devastating effects in terms of reducing the quality of life of older people. Muscle ageing is characterised by muscle atrophy and decreased capacity for muscle repair, including a reduction in the muscle stem cell pool that impedes recovery after injury. Histone deacetylase 11 (HDAC11) is the newest member of the HDAC family and it is highly expressed in skeletal muscle. Our group recently showed that genetic deficiency in HDAC11 increases skeletal muscle regeneration, mitochondrial function and globally improves muscle performance in young mice. Here, we explore for the first time the functional consequences of HDAC11 deficiency in old mice, in homeostasis and during muscle regeneration. Aged mice lacking HDAC11 show attenuated muscle atrophy and postsynaptic fragmentation of the neuromuscular junction, but no significant differences in the number or diameter of myelinated axons of peripheral nerves. Maintenance of the muscle stem cell reservoir and advanced skeletal muscle regeneration after injury are also observed. HDAC11 depletion enhances mitochondrial fatty acid oxidation and attenuates age-associated alterations in skeletal muscle fatty acid composition, reducing drastically the omega-6/omega-3 fatty acid ratio and improving significantly the omega-3 index, providing an explanation for improved muscle strength and fatigue resistance and decreased mortality. Taken together, our results point to HDAC11 as a new target for the treatment of sarcopenia. Importantly, selective HDAC11 inhibitors have recently been developed that could offer a new therapeutic approach to slow the ageing process.Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This work was supported by Ministerio de Economía y Competitividad (BFU2016-80748 to M.S.), Ministerio de Ciencia, Innovación y Universidades (PID2020-118730RB-I00 to M.S. and PID2022-143269OB-I00 to J.A.G-S.), Instituto de Salud Carlos III (PI22/00104 to G.N-G.) and Feder funds. R.O. was supported in part by AFM 23557 project; A.M-A. was supported by the BECAL National Programme of Scholarships Abroad Don Carlos Antonio López; P.M-M. was supported by the Programa Investigo 2022 INV-1 00008 (Generalitat de Catalunya); J.A.G-S. and G.N-G. were supported by a Miguel Servet Fellowship from the Instituto de Salud Carlos III (CP22/00078 and CPII19/00021, respectively) and E.H. was partially supported by BFU2016-80748.Peer reviewedSpringer NatureConferencia de Rectores de las Universidades EspañolasConsejo Superior de Investigaciones Científicas (España)Ministerio de Economía y Competitividad (España)Ministerio de Ciencia, Innovación y Universidades (España)Agencia Estatal de Investigación (España)Instituto de Salud Carlos IIIPrograma Nacional de Becas de Postgrado en el Exterior Don Carlos Antonio López (Paraguay)Generalitat de CatalunyaSuelves, Mònica [0000-0001-7095-5804]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202620262025info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/413401https://api.elsevier.com/content/abstract/scopus_id/105002353776reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-118730RB-I00info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2022-143269OB-I00info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica, Técnica y de Innovación 2021-2023/PI22%2F00104The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI 10.1007/s11357-025-01611-yhttps://doi.org/10.1007/s11357-025-01611-ySíinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/4134012026-05-22T06:33:51Z
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