The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index.
Restoration of telomerase activity rescues chromosomal instability and premature aging in Terc−/− mice with short telomeres
Open accessAbstract
Reconstitution of telomerase activity is proposed as a potential gene therapy to prevent, or rescue, age-related diseases produced by critical telomere shortening. However, it is not known whether or not short telomeres are irreversibly damaged. We addressed this by re-introducing telomerase in late generation telomerase-deficient mice, Terc-/-, which have short telomeres and show severe proliferative defects. For this, we have crossed these mice with Terc+/- mice and analyzed telomere length, chromosomal instability and premature aging of the progeny. The Terc-/- progeny had one set of chromosomes with normal telomeres, whereas the other set remained with critically short telomeres; these mice presented chromosomal instability and premature aging. In contrast, Terc+/- progeny showed all chromosomes with detectable telomeres, and did not show chromosomal instability or premature aging. These results prove that critically short telomeres can be rescued by telomerase, and become fully functional, thus rescuing premature aging. This has important implications for the future design of telomerase-based gene therapy of age-related diseases.
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“In particular, mice carrying a homozygous germline deletion of the telomerase RNA component gene (Terc−/−) exhibit critically short telomeres and a premature development of age-related pathologies from the second or third generation [8, 18–20, 51, 70, 72, 101, 103]”
From Senescence-related impairment of autophagy induces toxic intraneuronal amyloid-β accumulation in a mouse model of amyloid pathology (2023) · cites this paper as [101]
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“in turn responsible for chromosomal aberrations (Hemann et al, 2001; Samper et al, 2001).”
From Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer (2012) · cites this paper as Samper et al, 2001
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“The defects in proliferation and survival seen in late-generation telomerase-knockout mice appear to be caused by a subset of critically short telomeres, rather than a reduction in mean telomere length.”
From Telomeres and telomerase in cancer (2010) · cites this paper as [67]
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“The most persuasive evidence for a causal role comes from in vitro and in vivo manipulation of telomerase activity which impacts on TL and has been shown to enhance or reverse senescence and ageing-associated phenotypes35–39.”
From Identification of seven loci affecting mean telomere length and their association with disease (2013) · cites this paper as [38]
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Citations
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Metadata
- Authors
- Samper, E., Flores, J. M., & Blasco, M. A.
- Affiliations
- Centro Nacional de Biotecnología (ES)
- Universidad Complutense de Madrid (ES)
- ORCID
- Flores, Juana M
- Venue
- The EMBO Reports
- Published
- 2001-09-01
- Volume
- 2
- Issue
- 9
- Pages
- 800-807
- ISSN
- 1469-221X (ISSN-L)
- 1469-3178
- PMC
- PMC1084029
- OpenAlex
- W1984552013
- Cited by
- 263
- References
- 31
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 2 · 2023: 6 · 2022: 6 · 2021: 6 · 2020: 7 · 2019: 16 · 2018: 10 · 2017: 12 · 2016: 14 · 2015: 16 · 2014: 8 · 2013: 12 · 2012: 11
- FWCI
- 9.18
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- EMBO Reports (publishedVersion)
- PubMed Central (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Swiss Bridge Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › 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 › Molecular Biology › Nuclear Structure and Function
- Keywords
- telomerase, telomerase reconstitution, telomere shortening, chromosomal instability, premature aging, telomere length, gene therapy, age-related diseases
- MeSH terms
- Aging, Animals, Bone Marrow, Bone Marrow Cells, Chromosome Aberrations, Chromosomes, Crosses, Genetic, Genotype, Intestine, Small, Male, Mice, Transgenic, Phenotype, Testis, Y Chromosome, Telomere, In Situ Hybridization, Fluorescence, Telomerase, Mice
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