Adult Sox2+ stem cell exhaustion in mice results in cellular senescence and premature aging

Aging is characterized by a gradual functional decline of tissues with age. Adult stem and progenitor cells are responsible for tissue maintenance, repair, and regeneration, but during aging, this population of cells is decreased or its activity is reduced, compromising tissue integrity and causing...

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Autores: Vilas, Jéssica M., Carnero, Amancio, Silva-Alvarez, S. da, Ferreirós, Alba, González, Patricia, Gómez, María, Ortega, Sagrario, Serrano, Manuel, García-Caballero, Tomás, González-Barcia, M., Vidal, Anxo, Collado, Manuel
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/345254
Acceso en línea:http://hdl.handle.net/10261/345254
Access Level:acceso abierto
Palabra clave:Sox2
Aging
Adult stem cells
Stem cell exhaustion
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spelling Adult Sox2+ stem cell exhaustion in mice results in cellular senescence and premature agingVilas, Jéssica M.Carnero, AmancioSilva-Alvarez, S. daFerreirós, AlbaGonzález, PatriciaGómez, MaríaOrtega, SagrarioSerrano, ManuelGarcía-Caballero, TomásGonzález-Barcia, M.Vidal, AnxoCollado, ManuelSox2AgingAdult stem cellsStem cell exhaustionAging is characterized by a gradual functional decline of tissues with age. Adult stem and progenitor cells are responsible for tissue maintenance, repair, and regeneration, but during aging, this population of cells is decreased or its activity is reduced, compromising tissue integrity and causing pathologies that increase vulnerability, and ultimately lead to death. The causes of stem cell exhaustion during aging are not clear, and whether a reduction in stem cell function is a cause or a consequence of aging remains unresolved. Here, we took advantage of a mouse model of induced adult Sox2+ stem cell depletion to address whether accelerated stem cell depletion can promote premature aging. After a short period of partial repetitive depletion of this adult stem cell population in mice, we observed increased kyphosis and hair graying, and reduced fat mass, all of them signs of premature aging. It is interesting that cellular senescence was identified in kidney after this partial repetitive Sox2+ cell depletion. To confirm these observations, we performed a prolonged protocol of partial repetitive depletion of Sox2+ cells, forcing regeneration from the remaining Sox2+ cells, thereby causing their exhaustion. Senescence specific staining and the analysis of the expression of genetic markers clearly corroborated that adult stem cell exhaustion can lead to cellular senescence induction and premature aging.Work in the laboratory of M.C. is funded by an ISCIII and EU-FEDER grant (PI14/00554)Peer reviewedJohn Wiley & SonsInstituto de Salud Carlos IIIEuropean Commission202420242018info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/345254reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttps://doi.org/10.1111/acel.12834Noinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3452542026-05-22T06:33:51Z
dc.title.none.fl_str_mv Adult Sox2+ stem cell exhaustion in mice results in cellular senescence and premature aging
title Adult Sox2+ stem cell exhaustion in mice results in cellular senescence and premature aging
spellingShingle Adult Sox2+ stem cell exhaustion in mice results in cellular senescence and premature aging
Vilas, Jéssica M.
Sox2
Aging
Adult stem cells
Stem cell exhaustion
title_short Adult Sox2+ stem cell exhaustion in mice results in cellular senescence and premature aging
title_full Adult Sox2+ stem cell exhaustion in mice results in cellular senescence and premature aging
title_fullStr Adult Sox2+ stem cell exhaustion in mice results in cellular senescence and premature aging
title_full_unstemmed Adult Sox2+ stem cell exhaustion in mice results in cellular senescence and premature aging
title_sort Adult Sox2+ stem cell exhaustion in mice results in cellular senescence and premature aging
dc.creator.none.fl_str_mv Vilas, Jéssica M.
Carnero, Amancio
Silva-Alvarez, S. da
Ferreirós, Alba
González, Patricia
Gómez, María
Ortega, Sagrario
Serrano, Manuel
García-Caballero, Tomás
González-Barcia, M.
Vidal, Anxo
Collado, Manuel
author Vilas, Jéssica M.
author_facet Vilas, Jéssica M.
Carnero, Amancio
Silva-Alvarez, S. da
Ferreirós, Alba
González, Patricia
Gómez, María
Ortega, Sagrario
Serrano, Manuel
García-Caballero, Tomás
González-Barcia, M.
Vidal, Anxo
Collado, Manuel
author_role author
author2 Carnero, Amancio
Silva-Alvarez, S. da
Ferreirós, Alba
González, Patricia
Gómez, María
Ortega, Sagrario
Serrano, Manuel
García-Caballero, Tomás
González-Barcia, M.
Vidal, Anxo
Collado, Manuel
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Instituto de Salud Carlos III
European Commission
dc.subject.none.fl_str_mv Sox2
Aging
Adult stem cells
Stem cell exhaustion
topic Sox2
Aging
Adult stem cells
Stem cell exhaustion
description Aging is characterized by a gradual functional decline of tissues with age. Adult stem and progenitor cells are responsible for tissue maintenance, repair, and regeneration, but during aging, this population of cells is decreased or its activity is reduced, compromising tissue integrity and causing pathologies that increase vulnerability, and ultimately lead to death. The causes of stem cell exhaustion during aging are not clear, and whether a reduction in stem cell function is a cause or a consequence of aging remains unresolved. Here, we took advantage of a mouse model of induced adult Sox2+ stem cell depletion to address whether accelerated stem cell depletion can promote premature aging. After a short period of partial repetitive depletion of this adult stem cell population in mice, we observed increased kyphosis and hair graying, and reduced fat mass, all of them signs of premature aging. It is interesting that cellular senescence was identified in kidney after this partial repetitive Sox2+ cell depletion. To confirm these observations, we performed a prolonged protocol of partial repetitive depletion of Sox2+ cells, forcing regeneration from the remaining Sox2+ cells, thereby causing their exhaustion. Senescence specific staining and the analysis of the expression of genetic markers clearly corroborated that adult stem cell exhaustion can lead to cellular senescence induction and premature aging.
publishDate 2018
dc.date.none.fl_str_mv 2018
2024
2024
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/10261/345254
url http://hdl.handle.net/10261/345254
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv https://doi.org/10.1111/acel.12834
No
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv John Wiley & Sons
publisher.none.fl_str_mv John Wiley & Sons
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
repository.name.fl_str_mv
repository.mail.fl_str_mv
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