Activation of telomerase in human lymphocytes and hematopoietic progenitor cells
Abstract
This is the first report describing up-regulation of telomerase activity in human normal cells. Telomerase, a ribonucleoprotein enzyme, has been thought to be involved in maintaining telomere length stability in germline and most cancer cells, but not in normal cells. However, in the present study, we demonstrate that telomerase activity is detectable at low levels in normal human T and B cells, increases by in vitro mitogenic stimulation, increases in hematopoietic progenitor cells upon their proliferation and differentiation, and decreases with aging. Understanding the regulation of telomerase activity in normal cells may provide important insights not only into the mechanisms of normal cellular senescence but also into the mechanisms of telomerase activity deregulation as part of cancer development.
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No significant adverse effects on normal tissues have been reported so far, even in hematopoietic cells, which may be highly susceptible to Telomelysin due to telomerase-positive stem cells.
“Although we have to wait for the final report of the clinical trial, no significant adverse effects on normal tissues have been reported so far, even in hematopoietic cells, which may be highly susceptible to Telomelysin due to the presence of telomerase-positive stem cells. (35)”
From Understanding and exploiting <i>hTERT</i> promoter regulation for diagnosis and treatment of human cancers (2008) · cites this paper as [35]
Some normal cells, including some tissue stem cells, express relatively high levels of telomerase.
“We should consider the fact that some normal cells, including some tissue stem cells, express relatively high levels of telomerase, (35,36,117) raising questions regarding the safety of Telomelysin.”
From Understanding and exploiting <i>hTERT</i> promoter regulation for diagnosis and treatment of human cancers (2008) · cites this paper as [35]
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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
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BackgroundSelf-citationHeterogeneity in telomere length of human chromosomes
Lansdorp, P. M. (1996) · Human Molecular Genetics · doi:10.1093/hmg/5.5.685 · Cited by 879 · see citing works
Telomerase maintains telomere structure in normal human cells
Kenichi, M., Yu, E. Y., Shilagardi, K., Ben‐Porath, I., Currier, J. L., Metz, G. B., Brooks, M. W., Kaneko, S., Seishi, M., DeCaprio, J. A., et al. (2006) · Kanazawa University Repository for Academic Resources (DSpace) (Kanazawa University) · Cited by 738 · see citing works
Telomerase in the human organism
Collins, K., & Mitchell, J. R. (2002) · Oncogene · doi:10.1038/sj.onc.1205083 · Cited by 600 · see citing works
Cdc13p: A Single-Strand Telomeric DNA-Binding Protein with a Dual Role in Yeast Telomere Maintenance
Nugent, C. I., Hughes, T., Lue, N. F., & Lundblad, V. (1996) · Science · doi:10.1126/science.274.5285.249 · Cited by 601 · see citing works
Kilian, A., Bowtell, D. D. L., Abud, H. E., Hime, G. R., Venter, D. J., Keese, P., Duncan, E. L., Reddel, R. R., & Jefferson, R. (1997) · Human Molecular Genetics · doi:10.1093/hmg/6.12.2011 · Cited by 586 · see citing works
Telomere and telomerase in stem cells
Hiyama, E., & Hiyama, K. (2007) · British Journal of Cancer · doi:10.1038/sj.bjc.6603671 · Cited by 550 · see citing works
“TELOMERES AND TELOMERASE IN HEMATOPOIETIC STEM CELLS In the hematopoietic system, telomerase-expressing cells are stem cells with self-renewal potential and their early descendants (Hiyama et al., 1995; Morrison et al., 1996).”
BackgroundInfluentialSelf-citationThe biology of replicative senescence
Campisi, J. (1997) · European Journal of Cancer · doi:10.1016/s0959-8049(96)00058-5 · Cited by 538 · see citing works
Härle-Bachor, C., & Boukamp, P. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.13.6476 · Cited by 492 · see citing works
Kyo, S. (2000) · Nucleic Acids Research · doi:10.1093/nar/28.3.669 · Cited by 494 · see citing works
Disease states associated with telomerase deficiency appear earlier in mice with short telomeres
Herrera, E., Samper, E., Martín‐Caballero, J., Flores, J. M., Lee, H., & Blasco, M. A. (1999) · The EMBO Journal · doi:10.1093/emboj/18.11.2950 · Cited by 471 · see citing works
“…express telomerase, such as those of the hematopietic system, has been proposed to be due to down-regulation of telomerase activity with age (Hiyama et al., 1995) and/or to the possibility that the levels of telomerase activity present in those tissues are not sufficient to prevent telomere…”
BackgroundBeerman, I., Seita, J., Inlay, M. A., Weissman, I. L., & Rossi, D. J. (2014) · Cell Stem Cell · doi:10.1016/j.stem.2014.04.016 · Cited by 445 · see citing works
“…of HSCs (Cheshier et al., 1999; Foudi et al., 2009; Wilson et al., 2008), combined with the expression of telomerase in HSCs (Broccoli et al., 1995; Hiyama et al., 1995; Morrison et al., 1996), minimizes the introduction of replicationbased errors and uncapping of telomeres during replication…”
BackgroundLin, J., Epel, E., Cheon, J., Kroenke, C., Sinclair, E., Bigos, M., Wolkowitz, O., Mellon, S., & Blackburn, E. (2010) · Journal of Immunological Methods · doi:10.1016/j.jim.2009.09.012 · Cited by 426 · see citing works
“Hiyama et al. (1995) further examined telomerase activity in restingPBMCs from124 Japanese individuals ranging from 0 to 86 years.”
BackgroundRegulated expression of telomerase activity in human T lymphocyte development and activation.
Weng, N., Levine, B. L., June, C. H., & Hodes, R. J. (1996) · The Journal of Experimental Medicine · doi:10.1084/jem.183.6.2471 · Cited by 403 · see citing works
“These results are consistent with two recent reports of telomerase expression in human peripheral blood T lymphocytes (22, 23 ), and with the demonstration that telomerase activity is inducible in unfractionated PBMC with mitogen stimulation (23).'Telomerase may thus have a broad role in the process of lymphocyte deve…”
BackgroundResultInfluentialTelomerase activity, cell proliferation, and cancer
Greider, C. W. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.1.90 · Cited by 401 · see citing works
Chiu, C., Dragowska, W., Kim, N. W., Vaziri, H., Yui, J., Thomas, T. E., Harley, C. B., & Lansdorp, P. M. (1996) · STEM CELLS · doi:10.1002/stem.140239 · Cited by 388 · see citing works
Telomerase Activity in Hematopoietic Cells Is Associated with Self-Renewal Potential
Morrison, S. J., Prowse, K. R., Ho, P., & Weissman, I. L. (1996) · Immunity · doi:10.1016/s1074-7613(00)80316-7 · Cited by 394 · see citing works
Ex vivo enrichment of mesenchymal cell progenitors by fibroblast growth factor 2
Bianchi, G., Banfi, A., Mastrogiacomo, M., Notaro, R., Luzzatto, L., Cancedda, R., & Quarto, R. (2003) · Experimental Cell Research · doi:10.1016/s0014-4827(03)00138-1 · Cited by 374 · 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 Telomerase Activity in Immortal Cell Lines
Holt, S. E., Wright, W. E., & Shay, J. W. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.6.2932 · Cited by 361 · see citing works
“CD34(1) CD38 hematopoietic stem cells have very low levels of telomerase activity, while their dividing CD34(1) CD38(1) progeny have increased levels of telomerase activity (5, 14).”
Self-citationPawelec, G. (1998) · Frontiers in bioscience · doi:10.2741/a266 · Cited by 357 · see citing works
“(188) have shown that telomerase activity is detectable at very low levels in normal human T and B cells and that it increases greatly after mitogenic stimulation.”
Nair, S. K., Heiser, A., Boczkowski, D., Majumdar, A. S., Naoe, M., LEBKOWSKI, J. S., Vieweg, J., & Gilboa, E. (2000) · Nature Medicine · doi:10.1038/79519 · Cited by 348 · see citing works
“Telomerase activity is, however, present in proliferating tissues such as activated T and B cells, hematopoietic progenitors, germ cells and cells within intestinal and liver tissu”
BackgroundKyo, S., Takakura, M., Fujiwara, T., & Inoue, M. (2008) · Cancer Science · doi:10.1111/j.1349-7006.2008.00878.x · Cited by 347 · see citing works
Forsyth, N. R., Wright, W. E., & Shay, J. W. (2002) · Differentiation · doi:10.1046/j.1432-0436.2002.690412.x · Cited by 345 · see citing works
Self-citationStem cells and aging: expanding the possibilities
Rao, M. S. R. (2001) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(01)00224-x · Cited by 346 · see citing works
“Studies have shown that levels of telomerase activity increase in hematopoietic progenitor cells upon their proliferation and differentiation, and decrease with aging (Hiyama et al., 1995).”
BackgroundTelomere 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
Hodes, R. J., Hathcock, K. S., & Weng, N. (2002) · Nature reviews. Immunology · doi:10.1038/nri890 · Cited by 315 · see citing works
“This has been shown most extensively for lymphocyte”
BackgroundExpression of human telomerase subunits and correlation with telomerase activity in cervical cancer.
Takakura, M., Kyo, S., Kanaya, T., Tanaka, M., & Inoue, M. (1998) · PubMed · Cited by 296 · see citing works
Telomerase Regulation, Cell Cycle, and Telomere Stability in Primitive Hematopoietic Cells
Engelhardt, M. M., Kumar, R., Albanell, J., Pettengell, R., Han, W., & Moore, M. A. S. (1997) · Blood · doi:10.1182/blood.v90.1.182 · Cited by 297 · see citing works
Differential regulation of telomerase activity and telomerase RNA during multi-stage tumorigenesis
Blasco, M. A., Rizen, M., Greider, C. W., & Hanahan, D. (1996) · Nature Genetics · doi:10.1038/ng0296-200 · Cited by 284 · see citing works
Wolthers, K. C., Bea, G., Wisman, A., Otto, S. A., de Roda Husman, A.-M., Schaft, N., de Wolf, F., Goudsmit, J., Coutinho, R. A., van der Zee, A. G. J., et al. (1996) · Science · doi:10.1126/science.274.5292.1543 · Cited by 286 · see citing works
Progressive Telomere Shortening in Aplastic Anemia
Ball, S. E., Gibson, F. M., Rizzo, S., Tooze, J. A., Marsh, J. C. W., & Gordon‐Smith, E. C. (1998) · Blood · doi:10.1182/blood.v91.10.3582 · Cited by 288 · 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
Detection of Telomerase Activity in Malignant and Nonmalignant Skin Conditions
Taylor, R. S., Ramirez, R. D., Ogoshi, M., Chaffins, M. L., Piatyszek, M. A., & Shay, J. W. (1996) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12345811 · Cited by 267 · see citing works
Self-citationTelomere lengthening and telomerase activation during human B cell differentiation
Weng, N., Granger, L., & Hodes, R. J. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.20.10827 · Cited by 271 · see citing works
Mechanisms of human telomerase reverse transcriptase (hTERT) regulation: clinical impacts in cancer
Leao, R. R. N., Apolónio, J. D., Lee, D., Figueiredo, A., Tabori, U. Y., & Castelo‐Branco, P. (2018) · Journal of Biomedical Science · doi:10.1186/s12929-018-0422-8 · Cited by 266 · see citing works
Iwama, H., Ohyashiki, K., Ohyashiki, J. H., Hayashi, S., Yahata, N., Ando, K., Toyama, K., Hoshika, A., Takasaki, M., Mori, M., et al. (1998) · Human Genetics · doi:10.1007/s004390050711 · Cited by 264 · see citing works
“Circulating T (Hiyama et al. 1995; Pan et al. 1997) and B lymphocytes (Broccoli et al.”
BackgroundInfluentialSelf-citationThe genetics and clinical manifestations of telomere biology disorders
Savage, S. A., & Bertuch, A. A. (2010) · Genetics in Medicine · doi:10.1097/gim.0b013e3181f415b5 · Cited by 257 · see citing works
Cytotoxic T cell immunity against telomerase reverse transcriptase in humans
Minev, B., Hipp, J., Firat, H., Schmidt, J. D., Langlade‐Demoyen, P., & Zanetti, M. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.070560797 · Cited by 255 · see citing works
Valenzuela, H. (2002) · Clinical Immunology · doi:10.1006/clim.2002.5271 · Cited by 254 · see citing works
Telomere Biology and Cardiovascular Disease
Fuster, J. J., & Andrés, V. (2006) · Circulation Research · doi:10.1161/01.res.0000251281.00845.18 · Cited by 237 · see citing works
Telomerase activity: A biomarker of cell proliferation, not malignant transformation
Belair, C. D., Yeager, T. R., Lopez, P. M., & Reznikoff, C. A. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.25.13677 · Cited by 237 · see citing works
Liu, K., Schoonmaker, M. M., Levine, B. L., June, C. H., Hodes, R. J., & Weng, N.-P. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.9.5147 · Cited by 233 · see citing works
Liu, K., Hodes, R. J., & Weng, N. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.166.8.4826 · Cited by 234 · see citing works
“Stimulation of peripheral blood T cells through the TCR/CD3 complex alone or in combination with costimulatory receptor results in induction of telomerase activity (7, 17, 18).”
BackgroundRelationship between Physical Activity Level, Telomere Length, and Telomerase Activity
Ludlow, A. T., Zimmerman, J. B., Witkowski, S., Hearn, J. W., Hatfield, B. D., & Roth, S. M. (2008) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0b013e31817c92aa · Cited by 226 · see citing works
Diet, nutrition and telomere length
Paul, L. (2011) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2010.12.001 · Cited by 227 · see citing works
“Telomerase activity is also present in activated T-lymphocytes [8,9], although this does not result in maintenance of telomere length in T-lymphocytes but may partially compensate for loss of telomere repeats during cell division [10].”
BackgroundReplicative Aging and Gene Expression in Long-Term Cultures of Human Bone Marrow Stromal Cells
Banfi, A., Bianchi, G., Notaro, R., Luzzatto, L., Cancedda, R., & Quarto, R. (2002) · Tissue Engineering · doi:10.1089/107632702320934001 · Cited by 227 · see citing works
“21,35,36 Telomerase activity has also been detected in human hematopoietic progenitors 37,38 and in other progenitor cells obtained from different tissues.”
Kanaya, T., Kyo, S., Hamada, K., Takakura, M., Kitagawa, Y., Harada, H., & Inoue, M. (2000) · PubMed · Cited by 222 · see citing works
IL-7-Dependent Extrathymic Expansion of CD45RA+ T Cells Enables Preservation of a Naive Repertoire
Soares, M. V. D., Soares, D., Borthwick, N., Maini, M. K., Janossy, G., Salmon, M., & Akbar, A. N. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.161.11.5909 · Cited by 216 · see citing works
Ballew, B. J., & Savage, S. A. (2013) · Expert Review of Hematology · doi:10.1586/ehm.13.23 · Cited by 212 · see citing works
Selection and Extended Growth of Murine Epidermal Stem Cells in Culture
Bickenbach, J. R., & Chism, E. (1998) · Experimental Cell Research · doi:10.1006/excr.1998.4163 · Cited by 208 · see citing works
Telomerase Activity in Candidate Stem Cells From Fetal Liver and Adult Bone Marrow
Yui, J., Chiu, C.-P., & Lansdorp, P. M. (1998) · Blood · doi:10.1182/blood.v91.9.3255 · Cited by 216 · see citing works
Reassessing target antigens for adoptive T-cell therapy
Hinrichs, C. S., & Restifo, N. P. (2013) · Nature Biotechnology · doi:10.1038/nbt.2725 · Cited by 209 · see citing works
Role of Telomerase in Normal and Cancer Cells
Meyerson, M. M. (2000) · Journal of Clinical Oncology · doi:10.1200/jco.2000.18.13.2626 · Cited by 202 · see citing works
Telomerase activity is detected in pancreatic cancer but not in benign tumors.
Hiyama, E., Kodama, T. S., Shinbara, K., Iwao, T., Itoh, M., Hiyama, K., Shay, J. W., Matsuura, Y., & Yokoyama, T. (1997) · PubMed · Cited by 207 · see citing works
Self-citationWeng, N., Palmer, L. D., Levine, B. L., Lane, H. C., June, C. H., & Hodes, R. J. (1997) · Immunological Reviews · doi:10.1111/j.1600-065x.1997.tb01026.x · Cited by 203 · see citing works
Clinical utility of telomerase in cancer
Hiyama, E., & Hiyama, K. (2002) · Oncogene · doi:10.1038/sj.onc.1205070 · Cited by 202 · see citing works
Self-citationSon, N. H., Murray, S., Yanovski, J., Hodes, R. J., & Weng, N.-P. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.165.3.1191 · Cited by 200 · see citing works
Telomerase regulation during entry into the cell cycle in normal human T cells.
Buchkovich, K. J., & Greider, C. W. (1996) · Molecular Biology of the Cell · doi:10.1091/mbc.7.9.1443 · Cited by 198 · see citing works
In vivo telomere dynamics of human hematopoietic stem cells
Notaro, R., Cimmino, A., Tabarini, D., Rotoli, B., & Luzzatto, L. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.25.13782 · Cited by 196 · see citing works
Albanell, J., Engelhardt, M., Han, W., Moore, M. A. S., Lonardo, F., Rusch, V., Langenfeld, J., Klimstra, D., Venkatraman, E., & Dmitrovsky, E. (1997) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/89.21.1609 · Cited by 193 · see citing works
Resistance of mature T cells to oncogene transformation.
Newrzela, S., Cornils, K., Li, Z.-X., Baum, C., Brugman, M., Hartmann, M., Meyer, J., Hartmann, S., Hansmann, M., Fehse, B., et al. (2008) · Blood · doi:10.1182/blood-2007-12-128751 · Cited by 196 · see citing works
Harley, C. B. (2002) · Oncogene · doi:10.1038/sj.onc.1205076 · Cited by 193 · see citing works
The fetal programming of telomere biology hypothesis: an update
Entringer, S., de Punder, K., Buß, C., & Wadhwa, P. D. (2018) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2017.0151 · Cited by 189 · see citing works
Immunosenescence: Role and measurement in influenza vaccine response among the elderly
Targonski, P. V., Jacobson, R. M., & Poland, G. A. (2007) · Vaccine · doi:10.1016/j.vaccine.2007.01.025 · Cited by 186 · see citing works
Wiseman, D. H. (2010) · Transplantation and Cellular Therapy · doi:10.1016/j.bbmt.2010.10.010 · Cited by 183 · see citing works
“Telomerase expression is variably high in cells endowed with self-renewal capacity, including HSCs [150], and correlates strongly with histologic evidence of malignant cells in many tissues [151].”
BackgroundAlternative lengthening of telomeres is associated with chromosomal instability in osteosarcomas
Scheel, C., Schaefer, K., Jauch, A. S., Keller, M., Wai, D., Brinkschmidt, C., van Valen, F., Boecker, W., Dockhorn‐Dworniczak, B., & Poremba, C. (2001) · Oncogene · doi:10.1038/sj.onc.1204493 · Cited by 181 · see citing works
Clinical implications of telomerase in cancer
Kim, N. W. (1997) · European Journal of Cancer · doi:10.1016/s0959-8049(97)00057-9 · Cited by 180 · see citing works
Hou, M., Xu, D., Björkholm, M., & Gruber, A. (2001) · Clinical Chemistry · doi:10.1093/clinchem/47.3.519 · Cited by 175 · see citing works
Hiyama, E., & Hiyama, K. (2003) · Cancer Letters · doi:10.1016/s0304-3835(02)00709-7 · Cited by 191 · see citing works
Self-citationIn vivo imaging of lymph node metastasis with telomerase-specific replication-selective adenovirus
Kishimoto, H., Kojima, T., Watanabe, Y., Kagawa, S., Fujiwara, T., Uno, F., Teraishi, F., Kyo, S., Mizuguchi, H., Hashimoto, Y., et al. (2006) · Nature Medicine · doi:10.1038/nm1404 · Cited by 179 · see citing works
“Other possible explanations of false-positive detection include either that GFP protein itself was produced in the primary tumor spread into regional lymph nodes or that high doses of OBP-401 entered nodes and incidentally replicated in normal lymphocytes in that they have low telomerase activit”
BackgroundHypoxia Extends the Life Span of Vascular Smooth Muscle Cells through Telomerase Activation
Minamino, T., Mitsialis, S. A., & Kourembanas, S. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.10.3336-3342.2001 · Cited by 178 · see citing works
“Recent studies indicate that telomerase activity is also present in highly proliferative somatic cell types, such as activated lymphocytes (7).”
Telomere maintenance mechanisms and cellular immortalization
Colgin, L. M., & Reddel, R. R. (1999) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(99)80014-8 · Cited by 177 · see citing works
Yashima, K., Litzky, L. A., Kaiser, L. R., Rogers, T. E., Lam, S. C., Wistuba, I. I., Milchgrub, S., Srivastava, S., Piatyszek, M. A., Shay, J. W., et al. (1997) · PubMed · Cited by 175 · see citing works
Self-citationTelomerase Activity Concentrates in the Mitotically Active Segments of Human Hair Follicles
Ramirez, R. D., Wright, W. E., Shay, J. W., & Taylor, R. S. (1997) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12285654 · Cited by 174 · see citing works
Self-citationNiewisch, M. R., & Savage, S. A. (2019) · Expert Review of Hematology · doi:10.1080/17474086.2019.1662720 · Cited by 179 · see citing works
Kyo, S., & Inoue, M. (2002) · Oncogene · doi:10.1038/sj.onc.1205163 · Cited by 173 · see citing works
Hooijberg, E., Ruizendaal, J. J., Snijders, P. J. F., Taanman-Kueter, E. W., Walboomers, J. M. M., & Spits, H. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.165.8.4239 · Cited by 168 · see citing works
Telomerase-Based Pharmacologic Enhancement of Antiviral Function of Human CD8+ T Lymphocytes
Fauce, S. R., Jamieson, B. D., Chin, A. C., Mitsuyasu, R. T., Parish, S. T., Ng, H. L., Ramirez, C. M., Yang, O. O., Harley, C. B., & Effros, R. B. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.10.7400 · Cited by 170 · see citing works
Refining the telomere-telomerase hypothesis of aging and cancer
Holt, S. E., Shay, J. W., & Wright, W. E. (1996) · Nature Biotechnology · doi:10.1038/nbt0796-836 · Cited by 167 · see citing works
Self-citationLack of cell cycle regulation of telomerase activity in human cells
Holt, S. E., Aisner, D. L., Shay, J. W., & Wright, W. E. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.20.10687 · Cited by 166 · see citing works
Self-citationThe disparity between human cell senescence in vitro and lifelong replication in vivo
Rubin, H. (2002) · Nature Biotechnology · doi:10.1038/nbt0702-675 · Cited by 165 · see citing works
“For example, variable activities of telomerase occur in normal bone marrow and peripheral blood leukocyte”
BackgroundTelomerase and cancer: revisiting the telomere hypothesis
Autexier, C., & Greider, C. W. (1996) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(96)10042-6 · Cited by 166 · see citing works
Telomerase activity and telomere length in hepatocellular carcinoma and chronic liver disease
Kojima, H., Yokosuka, O., Imazeki, F., Saisho, H., & Omata, M. (1997) · Gastroenterology · doi:10.1053/gast.1997.v112.pm9024303 · Cited by 162 · see citing works
Telomerase in the early detection of cancer.
Shay, J. W., & Gazdar, A. F. (1997) · Journal of Clinical Pathology · doi:10.1136/jcp.50.2.106 · Cited by 160 · see citing works
Self-citationHiyama, E., Hiyama, K., Yokoyama, T., & Shay, J. W. (2001) · Neoplasia · doi:10.1038/sj.neo.7900134 · Cited by 162 · see citing works
Self-citationRegulation of the hTERT telomerase catalytic subunit by the c-Abl tyrosine kinase
Kharbanda, S. M., Kumar, V., Dhar, S., Pandey, P., Chen, C., Majumder, P. K., Yuan, Z.-M., Whang, Y. E., Strauss, W. M., Pandita, T. K., et al. (2000) · Current Biology · doi:10.1016/s0960-9822(00)00483-8 · Cited by 165 · see citing works
“Because telomerase activity is low in most somatic cells, telomeres shorten as cells progress through replicative cycles [9–13].”
Broccoli, D., Godley, L. A., Donehower, L. A., Varmus, H. E., & de Lange, T. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.7.3765 · Cited by 157 · see citing works
“Telomerase activity is upregulated upon mitogenic stimulation of human peripheral blood lymphocytes (31), increased during in vitro culturing of primary mouse cells (12), and repressed during terminal differentiation of human and mouse cell lines (56).”
BackgroundHuman diseases of telomerase dysfunction: insights into tissue aging
Garcia, C. K., Wright, W. E., & Shay, J. W. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm644 · Cited by 156 · see citing works
Self-citationTelomere attrition as ageing biomarker.
Bekaert, S., Meyer, T. D., & Oostveldt, P. V. (2005) · PubMed · Cited by 158 · see citing works
Regulation of Telomere Length and Telomerase in T and B Cells
Weng, N., Hathcock, K. S., & Hodes, R. J. (1998) · Immunity · doi:10.1016/s1074-7613(00)80597-x · Cited by 155 · see citing works
Molecular mechanisms of age-related hearing loss
Seidman, M. D., Ahmad, N., & Bai, U. (2002) · Ageing Research Reviews · doi:10.1016/s1568-1637(02)00004-1 · Cited by 154 · see citing works
Roles for c-Myc in Self-renewal of Hematopoietic Stem Cells
Satoh, Y., Matsumura, I., Tanaka, H., Ezoe, S., Sugahara, H., Mizuki, M., Shibayama, H., Ishiko, E., Ishiko, J., Nakajima, K., et al. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m400407200 · Cited by 154 · see citing works
Telomerase activation in normal B lymphocytes and non-Hodgkin's lymphomas
Norrback, K.-F., Dahlenborg, K., Carlsson, R., & Roos, G. (1996) · Blood · doi:10.1182/blood.v88.1.222.222 · Cited by 156 · see citing works
Armstrong, L., Saretzki, G., Peters, H., Wappler, I., Evans, J., Hole, N., von Zglinicki, T., & Lako, M. (2005) · Stem Cells · doi:10.1634/stemcells.2004-0269 · Cited by 153 · see citing works
Tahara, H., Yasui, W., Tahara, E., Fujimoto, J., Ito, K., Tamai, K., Nakayama, J., Ishikawa, F., Tahara, E., & Ide, T. (1999) · Oncogene · doi:10.1038/sj.onc.1202458 · Cited by 152 · see citing works
Understanding immunosenescence and its impact on vaccination of older adults
Allen, J. C., Toapanta, F. R., Chen, W. H., & Tennant, S. M. (2020) · Vaccine · doi:10.1016/j.vaccine.2020.11.002 · Cited by 157 · see citing works
“Since B and T cells undergo extensive clonal expansion throughout the duration of an immune response, several studies illustrate an ageassociated progressive shortening of telomeres that occurs as a consequence of activation and differentiation of lymphocytes [41, 42].”
BackgroundTelomerase regulation: not just flipping the switch
Aisner, D. L. (2002) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(01)00268-4 · Cited by 151 · see citing works
- Authors
- Hiyama, K., Hirai, Y., Kyoizumi, S., Akiyama, M., Hiyama, E., Piatyszek, M. A., Shay, J. W., Ishioka, S., & Yamakido, M.
- Affiliations
- Hiroshima University (JP)
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 1995-10
- Volume
- 155
- Issue
- 8
- Pages
- 3711-3715
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1516272650
- Cited by
- 853
- References
- 0
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 2 · 2023: 10 · 2022: 6 · 2021: 11 · 2020: 9 · 2019: 13 · 2018: 11 · 2017: 8 · 2016: 13 · 2015: 15 · 2014: 17 · 2013: 20 · 2012: 17
- FWCI
- 38.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG07992, R01AG007992)
- 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, telomerase activity, lymphocytes, T cells, B cells, hematopoietic progenitor cells, mitogen stimulation, aging, cellular senescence, telomere length, carcinogenesis, normal cells
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Aging, Base Sequence, Bone Marrow Cells, Cell Separation, Child, Child, Preschool, Enzyme Activation, Hematopoietic Stem Cells, Humans, Infant, Infant, Newborn, Leukocytes, Mononuclear, Lymphocyte Activation, Lymphocytes, Male, Middle Aged, Molecular Sequence Data, Telomerase
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