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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Telomerase activation and telomere-length maintenance allow bypass of senescence and lead to cell immortalization.
“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]
Telomere shortening in the absence of telomerase plays a critical role in signaling entry into senescence.
“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
Ectopically expressed hTERT maintains telomere length and allows unlimited growth.
“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
Ectopic expression of telomerase in normal human somatic cells results in telomere elongation, abrogation of replicative senescence, a normal karyotype and cellular immortalization.
“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]
Replicative senescence is due largely to erosion of telomeres, the protective structures that cap the ends of eukaryotic chromosomes.
“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]
Genetic validation experiments indicate that telomerase-mediated telomere maintenance is key to immortalization and continued proliferation in many human cancers.
“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
Transfection of cells with hTERT and subsequent expression of active telomerase extend the life spans of normal human fibroblasts and epithelial cells.
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
The serial cultivation of human diploid cell strains
Hayflick, L., & Moorhead, P. S. (1961) · Experimental Cell Research · doi:10.1016/0014-4827(61)90192-6 · Cited by 8,508 · see citing works
A biomarker that identifies senescent human cells in culture and in aging skin in vivo.
Dimri, G. P., Lee, X., Basile, G., Acosta, M., Scott, G., Roskelley, C., Medrano, E. E., Linskens, M., Rubelj, I., & Pereira-Smith, O. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.20.9363 · Cited by 7,477 · see citing works
Specific Association of Human Telomerase Activity with Immortal Cells and Cancer
Kim, N. W., Piatyszek, M. A., Prowse, K. R., Harley, C. B., West, M. D., Ho, P. L. C., Coviello, G. M., Wright, W. E., Weinrich, S. L., & Shay, J. W. (1994) · Science · doi:10.1126/science.7605428 · Cited by 7,091 · cited 2× · see citing works
“[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 · see citing works
Extension of Life-Span by Introduction of Telomerase into Normal Human Cells
Bodnar, A. G., Ouellette, M., Frolkis, M., Holt, S. E., Chiu, C.-P., Morin, G. B., Harley, C. B., Shay, J. W., Lichtsteiner, S., & Wright, W. E. (1998) · Science · doi:10.1126/science.279.5349.349 · Cited by 4,975 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
Self-citationMorgenstern, J. P., & Land, H. (1990) · Nucleic Acids Research · doi:10.1093/nar/18.12.3587 · Cited by 2,099 · see citing works
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× · see citing works
“[6–8].”
Olovnikov (1973) · doi:10.1016/0022-5193(73)90198-7 · Cited by 1,847 · see citing works
Meyerson, M., Counter, C. M., Eaton, E. N., Ellisen, L. W., Steiner, P., Caddle, S. D., Ziaugra, L., Beijersbergen, R. L., Davidoff, M. J., Liu, Q., et al. (1997) · Cell · doi:10.1016/s0092-8674(00)80538-3 · Cited by 1,784 · see citing works
Telomere reduction in human colorectal carcinoma and with ageing
Hastie, N. D., Dempster, M., Dunlop, M. G., Thompson, A. M., Green, D. K., & Allshire, R. C. (1990) · Nature · doi:10.1038/346866a0 · Cited by 1,650 · see citing works
Morin, G. B. (1989) · Cell · doi:10.1016/0092-8674(89)90035-4 · Cited by 1,495 · see citing works
Reverse Transcriptase Motifs in the Catalytic Subunit of Telomerase
Lingner, J., Hughes, T. R., Shevchenko, A., Mann, M., Lundblad, V., & Cech, T. R. (1997) · Science · doi:10.1126/science.276.5312.561 · Cited by 1,269 · see citing works
Telomere loss: mitotic clock or genetic time bomb?
Harley, C. B. (1991) · Mutation Research/DNAging · doi:10.1016/0921-8734(91)90018-7 · Cited by 1,139 · see citing works
Weinrich, S. L., Pruzan, R., Ma, L., Ouellette, M. M., Tesmer, V. M., Holt, S. E., Bodnar, A. G., Lichtsteiner, S., Kim, N. W., Trager, J. B., et al. (1997) · Nature Genetics · doi:10.1038/ng1297-498 · Cited by 963 · see citing works
Loss of telomeric DNA during aging of normal and trisomy 21 human lymphocytes.
Vaziri, H., Schächter, F., Uchida, I. A., Wei, L., Zhu, X., Effros, R. B., Cohen, D., & Harley, C. (1993) · PubMed · Cited by 734 · see citing works
Self-citationKim, N. (1997) · Nucleic Acids Research · doi:10.1093/nar/25.13.2595 · Cited by 688 · see citing works
Albritton, L. M., Tseng, L., Scadden, D. T., & Cunningham, J. M. (1989) · Cell · doi:10.1016/0092-8674(89)90134-7 · Cited by 687 · see citing works
Lendvay, T. S., Morris, D. K., Sah, J., Balasubramanian, B., & Lundblad, V. (1996) · Genetics · doi:10.1093/genetics/144.4.1399 · Cited by 505 · see citing works
The telomere hypothesis of cellular aging
Harley, C. B., Vaziri, H., Counter, C. M., & Allsopp, R. (1992) · Experimental Gerontology · doi:10.1016/0531-5565(92)90068-b · Cited by 493 · see citing works
Self-citationVaziri, H., West, M. D., Allsopp, R., Davison, T. S., Wu, Y., Arrowsmith, C. H., Poirier, G. G., & Benchimol, S. (1997) · The EMBO Journal · doi:10.1093/emboj/16.19.6018 · Cited by 384 · see citing works
Self-citationThe catalytic subunit of yeast telomerase
Counter, C. M., Meyerson, M. M., Eaton, E. N., & Weinberg, R. A. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.17.9202 · Cited by 229 · see citing works
Flagged first, then by citations
1 of the 25 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Hanahan, D., & Weinberg, R. A. (2000) · Cell · doi:10.1016/s0092-8674(00)81683-9 · Cited by 29,219 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
Longevity, Stress Response, and Cancer in Aging Telomerase-Deficient Mice
Rudolph, K. L., Chang, S., Lee, H.-W., Blasco, M., Gottlieb, G. J., Greider, C., & DePinho, R. A. (1999) · Cell · doi:10.1016/s0092-8674(00)80580-2 · Cited by 1,349 · see citing works
Aubert, G., & Lansdorp, P. M. (2008) · Physiological Reviews · doi:10.1152/physrev.00026.2007 · Cited by 1,188 · see citing works
p53- and ATM-Dependent Apoptosis Induced by Telomeres Lacking TRF2
Karlseder, J., Broccoli, D., Dai, Y., Hardy, S., & de Lange, T. (1999) · Science · doi:10.1126/science.283.5406.1321 · Cited by 1,086 · see citing works
Inhibition of telomerase limits the growth of human cancer cells
Hahn, W. C., Stewart, S. A., Brooks, M. W., York, S. G., Eaton, E. N., Kurachi, A. L., Beijersbergen, R. L., Knoll, J. H. M., Meyerson, M. M., & Weinberg, R. A. (1999) · Nature Medicine · doi:10.1038/13495 · Cited by 1,032 · see citing works
Chin, L., Artandi, S. E., Shen, Q., Tam, A., Lee, S.-L., Gottlieb, G. J., Greider, C. W., & DePinho, R. A. (1999) · Cell · doi:10.1016/s0092-8674(00)80762-x · Cited by 979 · see citing works
Telomeres and telomerase: three decades of progress
Shay, J. W., & Wright, W. E. (2019) · Nature Reviews Genetics · doi:10.1038/s41576-019-0099-1 · Cited by 924 · see citing works
Modelling the molecular circuitry of cancer
Hahn, W. C., & Weinberg, R. A. (2002) · Nature reviews. Cancer · doi:10.1038/nrc795 · Cited by 936 · see citing works
Human Telomerase and Its Regulation
Cong, Y.-S., Wright, W. E., & Shay, J. W. (2002) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.66.3.407-425.2002 · Cited by 898 · see citing works
Kojima, Y., Acar, A., Eaton, E. N., Mellody, K. T., Scheel, C., Ben‐Porath, I., Önder, T. T., Wang, Z. C., Richardson, A. L., Weinberg, R. A., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1013805107 · Cited by 851 · see citing works
Johnson, F. B., Sinclair, D. A., & Guarente, L. (1999) · Cell · doi:10.1016/s0092-8674(00)80567-x · Cited by 840 · see citing works
p53 is regulated by the lysine demethylase LSD1
Huang, J. L., Sengupta, R., Espejo, A. B., Lee, M. G., Dorsey, J. A., Richter, M., Opravil, S., Shiekhattar, R., Bedford, M. T., Jenuwein, T., et al. (2007) · Nature · doi:10.1038/nature06092 · Cited by 820 · see citing works
Simonsen, J. L., Rosada, C., Serakıncı, N., Justesen, J., Stenderup, K., Rattan, S. I. S., Jensen, T. G., & Kassem, M. S. (2002) · Nature Biotechnology · doi:10.1038/nbt0602-592 · Cited by 806 · see citing works
Absence of cancer–associated changes in human fibroblasts immortalized with telomerase
Morales, C. P., Holt, S. E., Ouellette, M. M., Kaur, K. J., Yan, Y., Wilson, K. S., White, M. A., Wright, W. E., & Shay, J. W. (1999) · Nature Genetics · doi:10.1038/5063 · Cited by 805 · see citing works
Regulation of Telomerase by Telomeric Proteins
Smogorzewska, A., & de Lange, T. (2004) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.73.071403.160049 · Cited by 796 · see citing works
Telomeres in cancer: tumour suppression and genome instability
Maciejowski, J., & de Lange, T. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.171 · Cited by 745 · see citing works
Microarray analysis of replicative senescence
Shelton, D. N., Chang, E., Whittier, P. S., Choi, D., & Funk, W. D. (1999) · Current Biology · doi:10.1016/s0960-9822(99)80420-5 · Cited by 764 · see citing works
Senescence and immortalization: role of telomeres and telomerase
Shay, J. W., & Wright, W. E. (2004) · Carcinogenesis · doi:10.1093/carcin/bgh296 · Cited by 729 · see citing works
Telomere shortening and apoptosis in telomerase-inhibited human tumor cells
Zhang, X., Mar, V., Zhou, W., Harrington, L., & Robinson, M. O. (1999) · Genes & Development · doi:10.1101/gad.13.18.2388 · Cited by 698 · see citing works
Counter, C. M., Hahn, W. C., Wei, W., Caddle, S. D., Beijersbergen, R. L., Lansdorp, P. M., Sedivy, J. M., & Weinberg, R. A. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.25.14723 · Cited by 649 · see citing works
Repression of p53 activity by Smyd2-mediated methylation
Huang, J. L., Perez-Burgos, L., Placek, B. J., Sengupta, R., Richter, M., Dorsey, J. A., Kubicek, S., Opravil, S., Jenuwein, T., & Berger, S. L. (2006) · Nature · doi:10.1038/nature05287 · Cited by 626 · see citing works
Enumeration of the Simian Virus 40 Early Region Elements Necessary for Human Cell Transformation
Hahn, W. C., Dessain, S. K., Brooks, M. W., King, J. E., Elenbaas, B., Sabatini, D. M., DeCaprio, J. A., & Weinberg, R. A. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.7.2111-2123.2002 · Cited by 603 · see citing works
Vonderheide, R. H., Hahn, W. C., Schultze, J. L., & Nadler, L. M. (1999) · Immunity · doi:10.1016/s1074-7613(00)80066-7 · Cited by 570 · see citing works
Comparative biology of mouse versus human cells: modelling human cancer in mice
Rangarajan, A., & Weinberg, R. A. (2003) · Nature reviews. Cancer · doi:10.1038/nrc1235 · Cited by 567 · see citing works
Connecting Chromosomes, Crisis, and Cancer
Maser, R. S., & DePinho, R. A. (2002) · Science · doi:10.1126/science.297.5581.565 · Cited by 561 · see citing works
Species- and cell type-specific requirements for cellular transformation
Rangarajan, A., Hong, S. J., Gifford, A., & Weinberg, R. A. (2004) · Cancer Cell · doi:10.1016/j.ccr.2004.07.009 · Cited by 555 · see citing works
Telomere length dynamics in human lymphocyte subpopulations measured by flow cytometry
Rufer, N., Dragowska, W. H., Thornbury, G., Roosnek, E. E., & Lansdorp, P. M. (1998) · Nature Biotechnology · doi:10.1038/nbt0898-743 · Cited by 547 · see citing works
Herbert, B.-S., Pitts, A. E., Baker, S. I., Hamilton, S. E., Wright, W. E., Shay, J. W., & Corey, D. R. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.25.14276 · Cited by 539 · see citing works
Functional requirement of p23 and Hsp90 in telomerase complexes.Preprint
Holt, S., Aisner, D., Baur, J. A., Tesmer, V. M., Dy, M., Ouellette, M., Trager, J., Morin, G., Toft, D., Shay, J., et al. (1999) · Genes & Development · doi:10.1101/gad.13.7.817 · Cited by 589 · see citing works
TIN2, a new regulator of telomere length in human cells
Kim, S.-H., Kaminker, P., & Campisi, J. (1999) · Nature Genetics · doi:10.1038/70508 · Cited by 525 · see citing works
Shay, J. W. (2001) · Human Molecular Genetics · doi:10.1093/hmg/10.7.677 · Cited by 517 · see citing works
Cong, Y. (1999) · Human Molecular Genetics · doi:10.1093/hmg/8.1.137 · Cited by 485 · see citing works
Extension of Cell Life-Span and Telomere Length in Animals Cloned from Senescent Somatic Cells
Lanza, R. P., Cibelli, J. B., Blackwell, C., Cristofalo, V. J., Francis, M. K., Baerlocher, G. M., Mak, J., Schertzer, M., Chavez, E. A., Sawyer, N., et al. (2000) · Science · doi:10.1126/science.288.5466.665 · Cited by 466 · see citing works
Putative telomere-independent mechanisms of replicative aging reflect inadequate growth conditions
Ramirez, R. D., Morales, C. P., Herbert, B.-S., Rohde, J. M., Passons, C., Shay, J. W., & Wright, W. E. (2001) · Genes & Development · doi:10.1101/gad.859201 · Cited by 444 · see citing works
Pro-senescence therapy for cancer treatment
Nardella, C., Clohessy, J. G., Alimonti, A., & Pandolfi, P. P. (2011) · Nature Reviews Cancer · doi:10.1038/nrc3057 · Cited by 437 · see citing works
Telomerase contributes to tumorigenesis by a telomere length-independent mechanism
Stewart, S. A., Hahn, W. C., O'Connor, B. F., Banner, E. N., Lundberg, A. S., Modha, P., Mizuno, H., Brooks, M. W., Fleming, M., Zimonjic, D. B., et al. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.182407599 · Cited by 431 · see citing works
Inhibition of Experimental Liver Cirrhosis in Mice by Telomerase Gene Delivery
Rudolph, K. L., Chang, S., Millard, M., Schreiber-Agus, N., & DePinho, R. A. (2000) · Science · doi:10.1126/science.287.5456.1253 · Cited by 424 · see citing works
Distinct requirements for Ras oncogenesis in human versus mouse cellsPreprint
Hamad, N. M., Elconin, J. H., Karnoub, A. E., Bai, W., Rich, J. N., Abraham, R. T., Der, C. J., & Counter, C. M. (2002) · Genes & Development · doi:10.17615/zkd7-3774 · Cited by 430 · see citing works
A highly selective telomerase inhibitor limiting human cancer cell proliferation
Damm, K., Hemmann, U., Garin‐Chesa, P., Hauel, N., Kauffmann, I., Priepke, H., Niestroj, C., Daiber, C., Enenkel, B., Guilliard, B., et al. (2001) · The EMBO Journal · doi:10.1093/emboj/20.24.6958 · Cited by 422 · see citing works
A multidimensional systems biology analysis of cellular senescence in aging and disease
Avelar, R. A., Ortega, J. G., Tacutu, R., Tyler, E. J., Bennett, D., Binetti, P., Budovsky, A., Chatsirisupachai, K., Johnson, E., Murray, A., et al. (2020) · Genome Biology · doi:10.1186/s13059-020-01990-9 · Cited by 399 · see citing works
Telomere dysfunction and tumour suppression: the senescence connection
Deng, Y., Chan, S. S., & Chang, S. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2393 · Cited by 411 · see citing works
Greenberg, R. A., O’Hagan, R. C., Deng, H., Xiao, Q., Hann, S. R., Adams, R. R., Lichtsteiner, S., Chin, L., Morin, G. B., & DePinho, R. A. (1999) · Oncogene · doi:10.1038/sj.onc.1202669 · Cited by 411 · see citing works
Wright, W. E., & Shay, J. W. (2000) · Nature Medicine · doi:10.1038/78592 · Cited by 398 · see citing works
Cellular senescence, cancer and aging: the telomere connection
Campisi, J., Kim, S.-H., Lim, C.-S., & Rubio, M. (2001) · Experimental Gerontology · doi:10.1016/s0531-5565(01)00160-7 · Cited by 400 · see citing works
The telomerase reverse transcriptase regulates chromatin state and DNA damage responses
Masutomi, K., Possemato, R., Wong, J. M. Y., Currier, J. L., Tóthová, Z., Manola, J. B., Ganesan, S., Lansdorp, P. M., Collins, K., & Hahn, W. C. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0503095102 · Cited by 381 · see citing works
Telomerase extends the lifespan of virus-transformed human cells without net telomere lengthening
Zhu, J., Wang, H., Bishop, J. M., & Blackburn, E. H. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.7.3723 · Cited by 381 · see citing works
DNA Ligase IV-Dependent NHEJ of Deprotected Mammalian Telomeres in G1 and G2
Smogorzewska, A., Karlseder, J., Holtgreve-Grez, H., Jauch, A. S., & de Lange, T. (2002) · Current Biology · doi:10.1016/s0960-9822(02)01179-x · Cited by 377 · see citing works
Shi, S., Gronthos, S., Chen, S., Reddi, A. H., Counter, C. M., Robey, P. G., & Wang, C.-Y. (2002) · Nature Biotechnology · doi:10.1038/nbt0602-587 · Cited by 375 · see citing works
Clusterin/Apolipoprotein J in human aging and cancer
Trougakos, I. P., & Gonos, E. S. (2002) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/s1357-2725(02)00041-9 · Cited by 376 · see citing works
Short Dysfunctional Telomeres Impair Tumorigenesis in the INK4aΔ2/3 Cancer-Prone Mouse
Greenberg, R. A., Chin, L., Femino, A., Lee, K.-H., Gottlieb, G. J., Singer, R. H., Greider, C. W., & DePinho, R. A. (1999) · Cell · doi:10.1016/s0092-8674(00)80761-8 · Cited by 367 · see citing works
T cells and aging january 2002 update
Pawelec, G. (2002) · Frontiers in bioscience · doi:10.2741/a831 · Cited by 368 · see citing works
Regulation of cellular senescence by p53
Itahana, K., Dimri, G., & Campisi, J. (2001) · European Journal of Biochemistry · doi:10.1046/j.1432-1327.2001.02228.x · Cited by 365 · see citing works
The Bmi-1 oncogene induces telomerase activity and immortalizes human mammary epithelial cells.
Dimri, G. P., Martínez‐Guitarte, J., Jacobs, J. J. L., Keblusek, P., Itahana, K., van Lohuizen, M., Campisi, J., Wazer, D. E., & Band, V. (2002) · PubMed · Cited by 361 · see citing works
Pawelec, G. (1998) · Frontiers in bioscience · doi:10.2741/a266 · Cited by 357 · see citing works
Historical claims and current interpretations of replicative aging
Wright, W. E., & Shay, J. W. (2002) · Nature Biotechnology · doi:10.1038/nbt0702-682 · Cited by 355 · see citing works
When cells get stressed: an integrative view of cellular senescence
Ben-Porath, I., & Weinberg, R. A. (2004) · Journal of Clinical Investigation · doi:10.1172/jci200420663 · Cited by 404 · see citing works
Mucin Gene Expression in Immortalized Human Corneal–Limbal and Conjunctival Epithelial Cell Lines
Gipson, I. K., Spurr-Michaud, S. J., Argüeso, P., Tisdale, A. S., Ng, T. F., & Russo, C. L. (2003) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.02-0851 · Cited by 345 · see citing works
Mamchaoui, K., Trollet, C., Bigot, A., Négroni, E., Chaouch, S., Wolff, A., Kandalla, P. K., Marie, S., Santo, J. P. D., Guily, J. L. S., et al. (2011) · Skeletal Muscle · doi:10.1186/2044-5040-1-34 · Cited by 338 · see citing works
Telomerase: A target for cancer therapeutics
Shay, J. W., & Wright, W. E. (2002) · Cancer Cell · doi:10.1016/s1535-6108(02)00159-9 · Cited by 330 · see citing works
Telomeres: Cancer to Human Aging
Stewart, S. A., & Weinberg, R. A. (2006) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.22.010305.104518 · Cited by 336 · see citing works
Erosion of the telomeric single-strand overhang at replicative senescence
Stewart, S. A., Ben-Porath, I., Carey, V. J., O'Connor, B. F., Hahn, W. C., & Weinberg, R. A. (2003) · Nature Genetics · doi:10.1038/ng1127 · Cited by 335 · see citing works
Telomerase prevents the accelerated cell ageing of Werner syndrome fibroblasts
Wyllie, F. S., Jones, C. J., Skinner, J. W., Haughton, M. F., Wallis, C., Wynford-Thomas, D., Faragher, R. G. A., & Kipling, D. (2000) · Nature Genetics · doi:10.1038/71630 · Cited by 332 · see citing works
Telomere elongation in induced pluripotent stem cells from dyskeratosis congenita patients
Agarwal, S., Loh, Y., McLoughlin, E. M., Huang, J.-J., Park, I.-H., Miller, J. D., Huo, H.-G., Okuka, M., dos Reis, R., Loewer, S., et al. (2010) · Nature · doi:10.1038/nature08792 · Cited by 335 · see citing works
Genes involved in senescence and immortalization
Lundberg, A. S., Hahn, W. C., Gupta, P., & Weinberg, R. A. (2000) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(00)00155-1 · Cited by 313 · see citing works
Immortal Human Pancreatic Duct Epithelial Cell Lines with Near Normal Genotype and Phenotype
Ouyang, H. W., Mou, L.-J., Luk, C. K., Liu, N., Karásková, J., Squire, J. A., & Tsao, M. (2000) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)64800-6 · Cited by 316 · see citing works
Telomere length homeostasis requires that telomerase levels are limiting
Cristofari, G., & Lingner, J. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7600952 · Cited by 315 · see citing works
p53-Dependent Transcriptional Repression of c-myc Is Required for G1 Cell Cycle Arrest
Ho, J. S. L., Ma, W., Mao, D. Y. L., & Benchimol, S. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.17.7423-7431.2005 · Cited by 312 · see citing works
Self-citationThe Pin2/TRF1-Interacting Protein PinX1 Is a Potent Telomerase Inhibitor
Zhou, X. Z., & Lu, K. P. (2001) · Cell · doi:10.1016/s0092-8674(01)00538-4 · Cited by 307 · see citing works
Mathon, N. F., & Lloyd, A. C. (2001) · Nature reviews. Cancer · doi:10.1038/35106045 · Cited by 306 · see citing works
Cellular senescence as a tumor-protection mechanism: the essential role of counting
Wright, W. E., & Shay, J. W. (2001) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(00)00163-5 · Cited by 306 · see citing works
Zhu, C., Mouly, V., Cooper, R. N., Mamchaoui, K., Bigot, A., Shay, J. W., Santo, J. P. D., Butler-Browne, G. S., & Wright, W. E. (2007) · Aging Cell · doi:10.1111/j.1474-9726.2007.00306.x · Cited by 301 · see citing works
Telomerase and the maintenance of chromosome ends
Bryan, T. M., & Cech, T. R. (1999) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(99)80043-x · Cited by 301 · see citing works
Control of the cell cycle and apoptosis
Weinberg, R. A., & Lundberg, A. S. (1999) · European Journal of Cancer · doi:10.1016/s0959-8049(99)00046-5 · Cited by 288 · see citing works
Robertson, D. M., Li, L., Fisher, S., Pearce, V. P., Shay, J. W., Wright, W. E., Cavanagh, H., & Jester, J. (2005) · Investigative Ophthalmology and Visual Science · doi:10.1167/iovs.04-0528 · Cited by 304 · see citing works
Wick, M., Zubov, D., & Hagen, G. (1999) · Gene · doi:10.1016/s0378-1119(99)00108-0 · Cited by 280 · see citing works
Ohtani, N., Yamakoshi, K., Takahashi, A., & Hara, E. (2004) · The Journal of Medical Investigation · doi:10.2152/jmi.51.146 · Cited by 276 · see citing works
Unger, R. E., Krump‐Konvalinkova, V., Peters, K., & Kirkpatrick, C. J. (2002) · Microvascular Research · doi:10.1006/mvre.2002.2434 · Cited by 277 · see citing works
Activity, function, and gene regulation of the catalytic subunit of telomerase (hTERT)
Poole, J. C., Andrews, L. G., & Tollefsbol, T. O. (2001) · Gene · doi:10.1016/s0378-1119(01)00440-1 · Cited by 275 · see citing works
Replicative senescence: a critical review
Cristofalo, V. J., Lorenzini, A., Allen, R. G., Torres, C. A., & Tresini, M. (2004) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2004.07.010 · Cited by 275 · see citing works
Subsenescent Telomere Lengths in Fibroblasts Immortalized by Limiting Amounts of Telomerase
Ouellette, M. M., Liao, M., Herbert, B., Johnson, M. D. D., Holt, S. E., Liss, H. S., Shay, J. W., & Wright, W. E. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.14.10072 · Cited by 272 · see citing works
Adriamycin-induced Senescence in Breast Tumor Cells Involves Functional p53 and Telomere Dysfunction
Elmore, L. W., Rehder, C. W., Di, X. M., McChesney, P. A., Jackson‐Cook, C. K., Gewirtz, D. A., & Holt, S. E. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m205477200 · Cited by 271 · see citing works
Johnson, F. B., Marciniak, R. A., McVey, M., Stewart, S. A., Hahn, W. C., & Guarente, L. (2001) · The EMBO Journal · doi:10.1093/emboj/20.4.905 · Cited by 269 · see citing works
From cells to organisms: can we learn about aging from cells in culture?
Campisi, J. (2001) · Experimental Gerontology · doi:10.1016/s0531-5565(00)00230-8 · Cited by 263 · see citing works
Accumulation of Short Telomeres in Human Fibroblasts Prior to Replicative Senescence
Martens, U. M., Chavez, E. A., Poon, S. S. S., Schmoor, C., & Lansdorp, P. M. (2000) · Experimental Cell Research · doi:10.1006/excr.2000.4823 · Cited by 263 · see citing works
Mitochondrial hTERT exacerbates free‐radical‐mediated mtDNA damage
Santos, J. H., Meyer, J. N., Škorvaga, M., Annab, L. A., & Houten, B. V. (2004) · Aging Cell · doi:10.1111/j.1474-9728.2004.00124.x · Cited by 264 · see citing works
A critical role for telomeres in suppressing and facilitating carcinogenesis
Artandi, S. E., & DePinho, R. A. (2000) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(99)00047-7 · Cited by 318 · see citing works
The aging process and potential interventions to extend life expectancy.
Tosato, M., Zamboni, V., Ferrini, A., & Cesari, M. (2007) · PubMed Central · Cited by 260 · see citing works
Akagi, T., Sasai, K., & Hanafusa, H. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1834876100 · Cited by 259 · see citing works
Xu, D., Wang, Q., Gruber, A., Björkholm, M., Chen, Z., Zaid, A., Selivanova, G., Peterson, C., Wiman, K. G., & Pisa, P. (2000) · Oncogene · doi:10.1038/sj.onc.1203890 · Cited by 257 · see citing works
Immortalization and transformation of primary human airway epithelial cells by gene transfer
Lundberg, A., Randell, S., Stewart, S. A., Elenbaas, B., Hartwell, K. A., Brooks, M., Fleming, M., Olsen, J., Miller, S., Weinberg, R., et al. (2002) · Oncogene · doi:10.1038/sj.onc.1205550 · Cited by 267 · see citing works
Induction of hTERT Expression and Telomerase Activity by Estrogens in Human Ovary Epithelium Cells
Misiti, S., Nanni, S., Fontemaggi, G., Cong, Y.-S., Wen, J., Hirte, H. W., Piaggio, G., Sacchi, A., Pontecorvi, A., Bacchetti, S., et al. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.11.3764-3771.2000 · Cited by 254 · see citing works
hTERT associates with human telomeres and enhances genomic stability and DNA repair
Sharma, G. G., Gupta, A. K. D., Wang, H., Scherthan, H., Dhar, S., Gandhi, V. V., Iliakis, G. E., Shay, J. W., Young, C. S. H., & Pandita, T. K. (2003) · Oncogene · doi:10.1038/sj.onc.1206063 · Cited by 254 · see citing works
Studies of the molecular mechanisms in the regulation of telomerase activity
Liu, J. (1999) · The FASEB Journal · doi:10.1096/fasebj.13.15.2091 · Cited by 253 · see citing works
Andrew, T., Aviv, A., Falchi, M., Surdulescu, G. L., Gardner, J. P., Lu, X., Kimura, M., Kato, B. S., Valdes, A. M., & Spector, T. D. (2006) · The American Journal of Human Genetics · doi:10.1086/500052 · Cited by 252 · see citing works
Stable Association of hsp90 and p23, but Not hsp70, with Active Human Telomerase
Forsythe, H. L., Jarvis, J. L., Turner, J. W., Elmore, L. W., & Holt, S. E. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.c100055200 · Cited by 245 · see citing works
Veldman, T., Liu, X., Yuan, H., & Schlegel, R. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1435900100 · Cited by 246 · see citing works
Chavez, S. L., Abrahams, V. M., Alvero, A. B., Aldo, P. B., Ma, Y., Guller, S. M., Romero, R. J., & Mor, G. (2009) · Placenta · doi:10.1016/j.placenta.2009.08.007 · Cited by 245 · see citing works
- 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
- 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 › 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
