Premature aging in telomerase-deficient zebrafish
Open accessAbstract
Summary: 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.
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Similar observations of decreased fertilization and developmental potential with short telomeres have been made in zebrafish and killifish.
“Similar observations have been made in zebrafish and killifish186,187.”
From Telomere dysfunction in ageing and age-related diseases (2022) · cites this paper as [186]
The Results section (‘Telomerase-deficient zebrafish can be bred for only one generation’; page unavailable) reports reduced offspring survival and developmental defects associated with shorter telomeres. The paper also reports premature infertility, but the passages found do not establish a decreased fertilization rate. This source studies zebrafish, not killifish; the citing sentence carries a second citation for that species. (LLM, conf=0.82)
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- Authors
- Anchelin, M., Alcaraz-Pérez, F., Martínez, C. M., Bernabé-García, M., Mulero, V., & Cayuela, M. L.
- Affiliations
- Hospital Universitario Virgen de la Arrixaca (ES)
- University Hospital Virgen de la Arrixaca, Murcia, Spain;
- University of Murcia, Murcia, Spain
- Corresponding author
- Cayuela, María L.
- Venue
- Disease Models & Mechanisms
- Publisher
- The Company of Biologists
- Published
- 2013-01-01
- Volume
- 6
- Issue
- 5
- Pages
- 1101-12
- ISSN
- 1754-8403 (ISSN-L)
- 1754-8411
- PMC
- PMC3759330
- OpenAlex
- W2112857608
- Cited by
- 114
- References
- 52
- Citations by year
- 2026: 4 · 2025: 12 · 2024: 11 · 2023: 9 · 2022: 12 · 2021: 7 · 2020: 13 · 2019: 10 · 2018: 11 · 2017: 7 · 2016: 6 · 2015: 8 · 2014: 2 · 2013: 2
- FWCI
- 4.18
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Disease Models & Mechanisms (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Hispana (publishedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Ministerio de Ciencia e Innovación
- Fundación para la Formación e Investigación Sanitarias de la Región de Murcia
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Zebrafish Biomedical Research Applications
- Keywords
- telomerase deficiency, premature aging, zebrafish, p53, dyskeratosis congenita, telomere shortening, lifespan, telomerase reactivation, apoptosis, spinal curvature, infertility
- MeSH terms
- Animals, Breeding, Chromosome Aberrations, Humans, Longevity, Male, Mutation, Testis, Zebrafish, Tumor Suppressor Protein p53, Telomere, Apoptosis, Telomerase, Aging, Premature, Zebrafish Proteins, Mice, Telomere Shortening
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