Delayed gamma H2AX foci disappearance in mammary epithelial cells from aged women reveals an age-associated DNA repair defect

Aging is a degenerative process in which genome instability plays a crucial role. To gain insight into the link between organismal aging and DNA repair capacity, we analyzed DNA double-strand break (DSB) resolution efficiency in human mammary epithelial cells from 12 healthy donors of young and old...

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Autores: Anglada, T, Repulles, J, Espinal, A, LaBarge, MA, Stampfer, MR, Genesca, A, Martin, M
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Recursos:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
Repositorio:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
OAI Identifier:oai:iibsantpau.fundanetsuite.com:p11782
Acesso em linha:https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=11782
http://ddd.uab.cat/record/226395
Access Level:acceso abierto
Palavra-chave:aging
double-strand break repair
gamma H2AX
human mammary epithelial cells
DNA damage
genome integrity
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spelling Delayed gamma H2AX foci disappearance in mammary epithelial cells from aged women reveals an age-associated DNA repair defectAnglada, TRepulles, JEspinal, ALaBarge, MAStampfer, MRGenesca, AMartin, Magingdouble-strand break repairgamma H2AXhuman mammary epithelial cellsDNA damagegenome integrityAging is a degenerative process in which genome instability plays a crucial role. To gain insight into the link between organismal aging and DNA repair capacity, we analyzed DNA double-strand break (DSB) resolution efficiency in human mammary epithelial cells from 12 healthy donors of young and old ages. The frequency of DSBs was measured by quantifying the number of gamma H2AX foci before and after 1Gy of gamma-rays and it was higher in cells from aged donors (ADs) at all times analyzed. At 24 hours after irradiation, ADs retained a significantly higher frequency of residual DSBs than young donors (YDs), which had already reached values close to basal levels. The kinetics of DSB induction and disappearance showed that cells from ADs and YDs repair DSBs with similar speed, although analysis of early times after irradiation indicate that a repair defect may lie within the firing of the DNA repair machinery in AD cells. Indeed, using a mathematical model we calculated a constant factor of delay affecting aged human epithelial cells repair kinetics. This defect manifests with the accumulation of DSBs that might eventually undergo illegitimate repair, thus posing a relevant threat to the maintenance of genome integrity in older individuals.IMPACT JOURNALS LLC2019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=11782http://ddd.uab.cat/record/226395Aging-USISSN: 19454589reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pauinstname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)Inglésinfo:eu-repo/semantics/openAccessoai:iibsantpau.fundanetsuite.com:p117822026-06-14T12:41:47Z
dc.title.none.fl_str_mv Delayed gamma H2AX foci disappearance in mammary epithelial cells from aged women reveals an age-associated DNA repair defect
title Delayed gamma H2AX foci disappearance in mammary epithelial cells from aged women reveals an age-associated DNA repair defect
spellingShingle Delayed gamma H2AX foci disappearance in mammary epithelial cells from aged women reveals an age-associated DNA repair defect
Anglada, T
aging
double-strand break repair
gamma H2AX
human mammary epithelial cells
DNA damage
genome integrity
title_short Delayed gamma H2AX foci disappearance in mammary epithelial cells from aged women reveals an age-associated DNA repair defect
title_full Delayed gamma H2AX foci disappearance in mammary epithelial cells from aged women reveals an age-associated DNA repair defect
title_fullStr Delayed gamma H2AX foci disappearance in mammary epithelial cells from aged women reveals an age-associated DNA repair defect
title_full_unstemmed Delayed gamma H2AX foci disappearance in mammary epithelial cells from aged women reveals an age-associated DNA repair defect
title_sort Delayed gamma H2AX foci disappearance in mammary epithelial cells from aged women reveals an age-associated DNA repair defect
dc.creator.none.fl_str_mv Anglada, T
Repulles, J
Espinal, A
LaBarge, MA
Stampfer, MR
Genesca, A
Martin, M
author Anglada, T
author_facet Anglada, T
Repulles, J
Espinal, A
LaBarge, MA
Stampfer, MR
Genesca, A
Martin, M
author_role author
author2 Repulles, J
Espinal, A
LaBarge, MA
Stampfer, MR
Genesca, A
Martin, M
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv aging
double-strand break repair
gamma H2AX
human mammary epithelial cells
DNA damage
genome integrity
topic aging
double-strand break repair
gamma H2AX
human mammary epithelial cells
DNA damage
genome integrity
description Aging is a degenerative process in which genome instability plays a crucial role. To gain insight into the link between organismal aging and DNA repair capacity, we analyzed DNA double-strand break (DSB) resolution efficiency in human mammary epithelial cells from 12 healthy donors of young and old ages. The frequency of DSBs was measured by quantifying the number of gamma H2AX foci before and after 1Gy of gamma-rays and it was higher in cells from aged donors (ADs) at all times analyzed. At 24 hours after irradiation, ADs retained a significantly higher frequency of residual DSBs than young donors (YDs), which had already reached values close to basal levels. The kinetics of DSB induction and disappearance showed that cells from ADs and YDs repair DSBs with similar speed, although analysis of early times after irradiation indicate that a repair defect may lie within the firing of the DNA repair machinery in AD cells. Indeed, using a mathematical model we calculated a constant factor of delay affecting aged human epithelial cells repair kinetics. This defect manifests with the accumulation of DSBs that might eventually undergo illegitimate repair, thus posing a relevant threat to the maintenance of genome integrity in older individuals.
publishDate 2019
dc.date.none.fl_str_mv 2019
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://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=11782
http://ddd.uab.cat/record/226395
url https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=11782
http://ddd.uab.cat/record/226395
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 IMPACT JOURNALS LLC
publisher.none.fl_str_mv IMPACT JOURNALS LLC
dc.source.none.fl_str_mv Aging-US
ISSN: 19454589
reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
instname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
instname_str Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
reponame_str r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
collection r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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