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Telomerase Is Required for Zebrafish Lifespan

2013-01-17Journal article Open access
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dc.contributor.authorHenriques, Catarina M.
dc.contributor.authorCarneiro, Madalena C.
dc.contributor.authorTenente, Inês M.
dc.contributor.authorJacinto, António
dc.contributor.authorFerreira, Miguel Godinho
dc.date.accessioned2015-10-30T10:54:59Z
dc.date.available2015-10-30T10:54:59Z
dc.date.issued2013-01-17
dc.description.abstractTelomerase activity is restricted in humans. Consequentially, telomeres shorten in most cells throughout our lives. Telomere dysfunction in vertebrates has been primarily studied in inbred mice strains with very long telomeres that fail to deplete telomeric repeats during their lifetime. It is, therefore, unclear how telomere shortening regulates tissue homeostasis in vertebrates with naturally short telomeres. Zebrafish have restricted telomerase expression and human-like telomere length. Here we show that first-generation tert(-/-) zebrafish die prematurely with shorter telomeres. tert(-/-) fish develop degenerative phenotypes, including premature infertility, gastrointestinal atrophy, and sarcopaenia. tert(-/-) mutants have impaired cell proliferation, accumulation of DNA damage markers, and a p53 response leading to early apoptosis, followed by accumulation of senescent cells. Apoptosis is primarily observed in the proliferative niche and germ cells. Cell proliferation, but not apoptosis, is rescued in tp53(-/-)tert(-/-) mutants, underscoring p53 as mediator of telomerase deficiency and consequent telomere instability. Thus, telomerase is limiting for zebrafish lifespan, enabling the study of telomere shortening in naturally ageing individuals.pt_PT
dc.description.sponsorshipFCT fellowships, Howard Hughes Medical Institute.pt_PT
dc.identifier10.1371/journal.pgen.1003214
dc.identifier.citationHenriques CM, Carneiro MC, Tenente IM, Jacinto A, Ferreira MG (2013) Telomerase Is Required for Zebrafish Lifespan. PLoS Genet 9(1): e1003214. doi:10.1371/journal.pgen.1003214pt_PT
dc.identifier.doi10.1371/journal.pgen.1003214
dc.identifier.urihttp://hdl.handle.net/10400.7/453
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherPLOSpt_PT
dc.relation.publisherversionhttp://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1003214pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectTelomerasept_PT
dc.subjectZebrafishpt_PT
dc.titleTelomerase Is Required for Zebrafish Lifespanpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FSAU-ORG%2F116826%2F2010/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FSAU-ONC%2F116821%2F2010/PT
oaire.citation.endPage13pt_PT
oaire.citation.issue1pt_PT
oaire.citation.startPage1pt_PT
oaire.citation.titlePLOS Geneticspt_PT
oaire.citation.volume9pt_PT
oaire.fundingStream3599-PPCDT
oaire.fundingStream3599-PPCDT
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublication5235261f-0465-4be9-929e-4cd01288a6fe
relation.isProjectOfPublication322214da-9ed1-436e-a507-eee1118be0b1
relation.isProjectOfPublication.latestForDiscovery5235261f-0465-4be9-929e-4cd01288a6fe

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