Premature aging in telomerase-deficient zebrafish

Anchelin, Monique; Alcaráz Pérez, Francisca; Bernabé García, Manuel; Cayuela, María L.; Martínez Cáceres, Carlos Manuel; Mulero Méndez, Victoriano Francisco

Publication:
Premature aging in telomerase-deficient zebrafish

dc.contributor.author	Anchelin, Monique
dc.contributor.author	Alcaráz Pérez, Francisca
dc.contributor.author	Bernabé García, Manuel
dc.contributor.author	Cayuela, María L.
dc.contributor.author	Martínez Cáceres, Carlos Manuel
dc.contributor.author	Mulero Méndez, Victoriano Francisco
dc.contributor.department	Anatomía y Anatomía Patológica Comparadas
dc.date.accessioned	2025-01-17T11:32:06Z
dc.date.available	2025-01-17T11:32:06Z
dc.date.issued	2013-09-01
dc.description	© 2013. Published by The Company of Biologists Ltd. This manuscript version is made available under the CC-BY 4.0 license http://creativecommons.org/licenses/by/4.0/ This document is the Published version of a Published Work that appeared in final form in Disease Models & Mechanism. To access the final edited and published work see https://doi.org/10.1242/dmm.011635	es
dc.description.abstract	The study of telomere biology is crucial to the understanding of aging and cancer. In the pursuit of greater knowledge in the field of human telomere biology, the mouse has been used extensively as a model. However, there are fundamental differences between mouse and human cells. Therefore, additional models are required. In light of this, we have characterized telomerase-deficient zebrafish (Danio rerio) as the second vertebrate model for human telomerase-driven diseases. We found that telomerase-deficient zebrafish show p53-dependent premature aging and reduced lifespan in the first generation, as occurs in humans but not in mice, probably reflecting the similar telomere length in fish and humans. Among these aging symptoms, spinal curvature, liver and retina degeneration, and infertility were the most remarkable. Although the second-generation embryos died in early developmental stages, restoration of telomerase activity rescued telomere length and survival, indicating that telomerase dosage is crucial. Importantly, this model also reproduces the disease anticipation observed in humans with dyskeratosis congenita (DC). Thus, telomerase haploinsufficiency leads to anticipation phenomenon in longevity, which is related to telomere shortening and, specifically, with the proportion of short telomeres. Furthermore, p53 was induced by telomere attrition, leading to growth arrest and apoptosis. Importantly, genetic inhibition of p53 rescued the adverse effects of telomere loss, indicating that the molecular mechanisms induced by telomere shortening are conserved from fish to mammals. The partial rescue of telomere length and longevity by restoration of telomerase activity, together with the feasibility of the zebrafish for high-throughput chemical screening, both point to the usefulness of this model for the discovery of new drugs able to reactivate telomerase in individuals with DC.	es
dc.format	application/pdf	es
dc.format.extent	12	es
dc.identifier.citation	Disease Models & Mechanism, 2013, Vol. 6 (5), pp. 1101-1112
dc.identifier.doi	https://doi.org/10.1242/dmm.011635
dc.identifier.issn	Print: 1754-8403
dc.identifier.issn	Electronic: 1754-8411
dc.identifier.uri	http://hdl.handle.net/10201/148681
dc.language	eng	es
dc.publisher	The Company of Biologists	es
dc.relation	This work was supported by the Spanish Ministry of Science and Innovation (PI10/00878), Fundación Séneca from the regional government of Murcia, Spain (CARM, grant 08760/PI/08), Fundación para la Formación e Investigación Sanitarias de la Región de Murcia, Spain (fellowships to F.A.-P.), and RED RTICC (RD07/0020/0023).	es
dc.relation.publisherversion	https://journals.biologists.com/dmm/article/6/5/1101/3558/Premature-aging-in-telomerase-deficient-zebrafish	es
dc.rights	info:eu-repo/semantics/openAccess	es
dc.rights	Atribución 4.0 Internacional	*
dc.rights.uri	http://creativecommons.org/licenses/by/4.0/	*
dc.title	Premature aging in telomerase-deficient zebrafish	es
dc.type	info:eu-repo/semantics/article	es
dspace.entity.type	Publication	es
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