Henriques, C.M., Carneiro, M.C., Tenente, I.M. et al. (2 more authors) (2013) Telomerase is required for zebrafish lifespan. PLoS Genetics, 9 (1). ISSN 1553-7390
Abstract
Telomerase 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.
Metadata
Item Type: | Article |
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Copyright, Publisher and Additional Information: | Copyright 2013 Henriques et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Department of Human Metabolism (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 30 Sep 2015 15:10 |
Last Modified: | 03 Nov 2016 02:13 |
Published Version: | https://doi.org/10.1371/journal.pgen.1003214 |
Status: | Published |
Publisher: | Public Library of Science |
Refereed: | Yes |
Identification Number: | 10.1371/journal.pgen.1003214 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:88709 |