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, R, Cardús, A, Gomis-Coloma, C, Balanyà-Segura, M, Mercado-Amarilla, A, Maestre-Mora, P, Poveda-Sabuco, A, Domingo, JC, Nogales-Gadea, G, Gomez-Sanchez, JA, Hurtado, E, Suelves, M
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL)
Repositorio:r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante
OAI Identifier:oai:isabial.fundanetsuite.com:p11211
Acceso en línea:https://isabial.portalinvestigacion.com/publicaciones11211
https://doi.org/10.1007/s11357-025-01611-y
Access Level:acceso abierto
Palabra clave:HDAC11
Sarcopenia
Muscle atrophy
Skeletal muscle regeneration
Fatty acid oxidation
Omega-6/omega-3 fatty acid ratio
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spelling HDAC11 deficiency regulates age-related muscle decline and sarcopeniaOdria, RCardús, AGomis-Coloma, CBalanyà-Segura, MMercado-Amarilla, AMaestre-Mora, PPoveda-Sabuco, ADomingo, JCNogales-Gadea, GGomez-Sanchez, JAHurtado, ESuelves, MHDAC11SarcopeniaMuscle atrophySkeletal muscle regenerationFatty acid oxidationOmega-6/omega-3 fatty acid ratioSarcopenia, 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.SPRINGER2025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://isabial.portalinvestigacion.com/publicaciones11211https://doi.org/10.1007/s11357-025-01611-yGeroScienceISSN: 25092715ISSNe: 25092723reponame:r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicanteinstname:Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL)Inglésinfo:eu-repo/semantics/openAccessoai:isabial.fundanetsuite.com:p112112026-06-12T10:20:37Z
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, R
HDAC11
Sarcopenia
Muscle atrophy
Skeletal muscle regeneration
Fatty acid oxidation
Omega-6/omega-3 fatty acid ratio
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, R
Cardús, A
Gomis-Coloma, C
Balanyà-Segura, M
Mercado-Amarilla, A
Maestre-Mora, P
Poveda-Sabuco, A
Domingo, JC
Nogales-Gadea, G
Gomez-Sanchez, JA
Hurtado, E
Suelves, M
author Odria, R
author_facet Odria, R
Cardús, A
Gomis-Coloma, C
Balanyà-Segura, M
Mercado-Amarilla, A
Maestre-Mora, P
Poveda-Sabuco, A
Domingo, JC
Nogales-Gadea, G
Gomez-Sanchez, JA
Hurtado, E
Suelves, M
author_role author
author2 Cardús, A
Gomis-Coloma, C
Balanyà-Segura, M
Mercado-Amarilla, A
Maestre-Mora, P
Poveda-Sabuco, A
Domingo, JC
Nogales-Gadea, G
Gomez-Sanchez, JA
Hurtado, E
Suelves, M
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv HDAC11
Sarcopenia
Muscle atrophy
Skeletal muscle regeneration
Fatty acid oxidation
Omega-6/omega-3 fatty acid ratio
topic HDAC11
Sarcopenia
Muscle atrophy
Skeletal muscle regeneration
Fatty acid oxidation
Omega-6/omega-3 fatty acid ratio
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
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://isabial.portalinvestigacion.com/publicaciones11211
https://doi.org/10.1007/s11357-025-01611-y
url https://isabial.portalinvestigacion.com/publicaciones11211
https://doi.org/10.1007/s11357-025-01611-y
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv SPRINGER
publisher.none.fl_str_mv SPRINGER
dc.source.none.fl_str_mv GeroScience
ISSN: 25092715
ISSNe: 25092723
reponame:r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante
instname:Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL)
instname_str Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL)
reponame_str r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante
collection r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante
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