The DOI matches its Crossref record; 24 of the 25 references it cites were found in a registry or an index.
Reconstitution of telomerase activity in normal human cells leads to elongation of telomeres and extended replicative life span
Open accessAbstract
Normal somatic cells have a finite life span [1] and lose telomeric DNA, present at the ends of chromosomes, each time they divide as a function of age in vivo or in culture [2-4]. In contrast, many cancer cells and cell lines established from tumours maintain their telomere length by activation of an RNA-protein complex called telomerase, an enzyme originally discovered in Tetrahymena [5], that synthesizes telomeric repeats [6-8]. These findings have led to the formation of the 'telomere hypothesis', which proposes that critical shortening of telomeric DNA due to the end-replication problem [9] is the signal for the initiation of cellular senescence [10,11]. In yeast, the EST2 gene product, the catalytic subunit of telomerase, is essential for telomere maintenance in vivo [12-14]. The recent cloning of the cDNA encoding the catalytic subunit of human telomerase (hTERT) [15,16] makes it possible to test the telomere hypothesis. In this study, we expressed hTERT in normal human diploid fibroblasts, which lack telomerase activity, to determine whether telomerase activity could be reconstituted leading to extension of replicative life span. Our results show that retroviral-mediated expression of hTERT resulted in functional telomerase activity in normal aging human cells. Moreover, reconstitution of telomerase activity in vivo led to an increase in the length of telomeric DNA and to extension of cellular life span. These findings provide direct evidence in support of the telomere hypothesis, indicating that telomere length is one factor that can determine the replicative life span of human cells.
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In the citing paper
“We now know that the endpoint of this proliferative limit, termed replicative senescence, is due largely to erosion of telomeres, protective structures that cap the end of all eukaryotic chromosomes.”
From Telomere dysfunction and tumour suppression: the senescence connection (2008) · cites this paper as [4]
Experimental — accuracy not yet measuredIn the citing paper
“Telomerase activation and the resulting telomere-length maintenance leads to the bypass of senescence and ultimately to cell immortalization23,26,27.”
From Telomeres in cancer: tumour suppression and genome instability (2017) · cites this paper as [27]
In the citing paper
“Thus, telomere shortening in the absence of telomerase plays a critical role in signaling entry into senescence”
From p53 Deficiency Rescues the Adverse Effects of Telomere Loss and Cooperates with Telomere Dysfunction to Accelerate Carcinogenesis (1999) · cites this paper as Vaziri and Benchimol 1998
In the citing paper
“Ectopically expressed hTERT maintains telomere length and allows unlimited growth (Bodnar et al. 1998; Counter et al. 1998; Vaziri and Benchimol 1998”
From p53 Deficiency Rescues the Adverse Effects of Telomere Loss and Cooperates with Telomere Dysfunction to Accelerate Carcinogenesis (1999) · cites this paper as Vaziri and Benchimol 1998
In the citing paper
“Activation of telomerase results in telomere elongation, abrogation of replicative senescence, a normal karyotype and cellular immortalization.”
From Telomere dysfunction and tumour suppression: the senescence connection (2008) · cites this paper as [4]
In the citing paper
“A number of genetic validation experiments indicate that telomere maintenance by the enzyme telomerase is a key event in the immortalization process and the continuous proliferation of a large proportion of human cancers (Bodnar et al., 1998;Vaziri and Benchimol, 1998;Hahn et al., 1999a).”
From A highly selective telomerase inhibitor limiting human cancer cell proliferation (2001) · cites this paper as Vaziri and Benchimol, 1998
In the citing paper
“transfection of cells with the gene encoding the human telomerase reverse transcriptase component (hTERT) and subsequent expression of active telomerase have been shown to extend the life spans of normal human fibroblasts and epithelial cells (25–27).”
From Inhibition of human telomerase in immortal human cells leads to progressive telomere shortening and cell death (1999) · cites this paper as [26]
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Citations
Cites
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Specific Association of Human Telomerase Activity with Immortal Cells and Cancer
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“[6–8].”
Telomeres shorten during ageing of human fibroblasts
Harley, C. B., Futcher, A. B., & Greider, C. W. (1990) · Nature · doi:10.1038/345458a0 · Cited by 5,750
Extension of Life-Span by Introduction of Telomerase into Normal Human Cells
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Identification of a specific telomere terminal transferase activity in tetrahymena extracts
Greider, C. W., & Blackburn, E. H. (1985) · Cell · doi:10.1016/0092-8674(85)90170-9 · Cited by 3,400
Telomerase Catalytic Subunit Homologs from Fission Yeast and Human
Nakamura, T. M., Morin, G. B., Chapman, K. B., Weinrich, S. L., Andrews, W. H., Lingner, J., Harley, C. B., & Cech, T. R. (1997) · Science · doi:10.1126/science.277.5328.955 · Cited by 2,256
Telomere length predicts replicative capacity of human fibroblasts.
Allsopp, R. C., Vaziri, H., Patterson, C., Goldstein, S., Younglai, E. V., Futcher, A. B., Greider, C. W., & Harley, C. B. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.21.10114 · Cited by 2,200
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Counter, C. M., Avilion, A. A., LeFeuvre, C. E., Stewart, N. G., Greider, C. W., Harley, C. B., & Bacchetti, S. (1992) · The EMBO Journal · doi:10.1002/j.1460-2075.1992.tb05245.x · Cited by 2,096 · cited 1×
“[6–8].”
Research works printed but not linked: 1
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Cited by
Sorted by citations
Hanahan, D., & Weinberg, R. A. (2000) · Cell · doi:10.1016/s0092-8674(00)81683-9 · Cited by 29,219
The essence of senescence: Figure 1.
Kuilman, T., Michaloglou, C., Mooi, W. J., & Peeper, D. S. (2010) · Genes & Development · doi:10.1101/gad.1971610 · Cited by 2,038
How Shelterin Protects Mammalian Telomeres
Palm, W., & de Lange, T. (2008) · Annual Review of Genetics · doi:10.1146/annurev.genet.41.110306.130350 · Cited by 1,802
Reversal of human cellular senescence: roles of the p53 and p16 pathways
Beauséjour, C. M., Krtolica, A., Galimi, F., Narita, M., Lowe, S. W., Yaswen, P., & Campisi, J. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg417 · Cited by 1,457
Longevity, Stress Response, and Cancer in Aging Telomerase-Deficient Mice
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Metadata
- Authors
- Vaziri, H., & Benchimol, S.
- Affiliations
- University of Toronto (CA)
- Corresponding author
- Benchimol, Samuel
- ORCID
- Benchimol, Samuel
- Venue
- Current Biology
- Publisher
- Elsevier BV
- Published
- 1998-02
- Volume
- 8
- Issue
- 5
- Pages
- 279-282
- ISSN
- 0960-9822 (ISSN-L)
- OpenAlex
- W2100550233
- Cited by
- 1,003
- References
- 25
- Citations by year
- 2026: 4 · 2025: 11 · 2024: 12 · 2023: 8 · 2022: 13 · 2021: 11 · 2020: 12 · 2019: 15 · 2018: 9 · 2017: 15 · 2016: 20 · 2015: 27 · 2014: 17 · 2013: 28 · 2012: 31
- FWCI
- 48.65
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Current Biology (publishedVersion)
- PubMed (publishedVersion)
- 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, hTERT, telomere length, replicative lifespan, cellular senescence, telomere maintenance, retroviral gene transfer, human diploid fibroblasts, telomeric DNA, end-replication problem
- MeSH terms
- Animals, Catalysis, Cells, Cultured, DNA Replication, DNA-Binding Proteins, Fibroblasts, Humans, Protein Conformation, Proteins, Retroviridae, RNA, Tetrahymena, Telomere, Cellular Senescence, Telomerase
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