Evidence for a mitotic clock in human hematopoietic stem cells: loss of telomeric DNA with age.
Open accessAbstract
The proliferative life-span of the stem cells that sustain hematopoiesis throughout life is not known. It has been proposed that the sequential loss of telomeric DNA from the ends of human chromosomes with each somatic cell division eventually reaches a critical point that triggers cellular senescence. We now show that candidate human stem cells with a CD34+CD38lo phenotype that were purified from adult bone marrow have shorter telomeres than cells from fetal liver or umbilical cord blood. We also found that cells produced in cytokine-supplemented cultures of purified precursor cells show a proliferation-associated loss of telomeric DNA. These findings strongly suggest that the proliferative potential of most, if not all, hematopoietic stem cells is limited and decreases with age, a concept that has widespread implications for models of normal and abnormal hematopoiesis as well as gene therapy.
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Telomeres shorten progressively in human HSCs from fetal liver, cord blood, or adult bone marrow, and this is linked to a strongly reduced proliferative potential.
“telomeres progressively shorten in human HSCs isolated from fetal liver, cord blood, or adult bone marrow, which is associated with a strongly reduced proliferative potential.”
From Aging of hematopoietic stem cells (2018) · cites this paper as [26]
In human somatic cells with high telomerase activity, such as haematopoietic stem cells, telomeres usually shorten with each division and with age.
“Even in somatic human cells that are naturally enriched for telomerase activity, such as haematopoietic stem cells (HSCs), telomeres typically become shorter with each cell division and with age42,43.”
From The telomere syndromes (2012) · cites this paper as [43]
Cites
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
Self-citationStructure and function of telomeres
Blackburn, E. H. (1991) · Nature · doi:10.1038/350569a0 · Cited by 3,596 · 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
Moyzis, R. K., Buckingham, J. M., Cram, L. S., Dani, M. A. C., Deaven, L. L., Jones, M. D., Meyne, J., Ratliff, R. L., & Wu, J. R. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.18.6622 · Cited by 2,326 · 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-citationCounter, 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 · see citing works
Self-citationOlovnikov (1973) · doi:10.1016/0022-5193(73)90198-7 · Cited by 1,847 · 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
Civin, C., Strauss, L. C., Brovall, C., Fackler, M., Schwartz, J. F., & Shaper, J. H. (1984) · The Journal of Immunology · doi:10.4049/jimmunol.133.1.157 · Cited by 1,200 · 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
Self-citationIsolation of a candidate human hematopoietic stem-cell population.
Baum, C. M., Weissman, I. L., Tsukamoto, A. S., Buckle, A., & Péault, B. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.7.2804 · Cited by 1,084 · see citing works
A mutant with a defect in telomere elongation leads to senescence in yeast
Lundblad, V., & Szostak, J. W. (1989) · Cell · doi:10.1016/0092-8674(89)90132-3 · Cited by 909 · see citing works
Developmental potential and dynamic behavior of hematopoietic stem cells
Lemischka, I. R., Raulet, D. H., & Mulligan, R. C. (1986) · Cell · doi:10.1016/0092-8674(86)90566-0 · Cited by 880 · see citing works
Terstappen, L. W. M. M., Huang, S., Safford, M., Lansdorp, P., & Loken, M. R. (1991) · Blood · doi:10.1182/blood.v77.6.1218.1218 · Cited by 845 · see citing works
Self-citationLoss of a yeast telomere: Arrest, recovery, and chromosome loss
Sandell, L. J. (1993) · Cell · doi:10.1016/0092-8674(93)90493-a · Cited by 787 · 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-citationTelomerase activity in human ovarian carcinoma.
Counter, C. M., Hirte, H. W., Bacchetti, S., & Harley, C. B. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.8.2900 · Cited by 677 · see citing works
Self-citationAbramson, S. B., Miller, R. G., & Phillips, R. A. (1977) · The Journal of Experimental Medicine · doi:10.1084/jem.145.6.1567 · Cited by 568 · see citing works
[Principle of marginotomy in template synthesis of polynucleotides].
Olovnikov, A. M. (1971) · PubMed · Cited by 567 · see citing works
Yudkin, J. S. (1972) · Nature · doi:10.1038/239197a0 · Cited by 543 · see citing works
Broxmeyer, H. E., Hangoc, G., Cooper, S. H., Ribeiro, R. C., Graves, V. L., Yöder, M. C., Wagner, J. E., Vadhan‐Raj, S., Benninger, L., & Rubinstein, P. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.9.4109 · Cited by 490 · see citing works
Expression of Thy-1 on human hematopoietic progenitor cells.
Craig, W., Kay, R., Cutler, R. L., & Lansdorp, P. M. (1993) · The Journal of Experimental Medicine · doi:10.1084/jem.177.5.1331 · Cited by 464 · see citing works
Self-citationIn vivo loss of telomeric repeats with age in humans
Lindsey, J., McGill, N. I., Lindsey, L. A., Green, D. K., & Cooke, H. J. (1991) · Mutation Research/DNAging · doi:10.1016/0921-8734(91)90032-7 · Cited by 463 · see citing works
Ontogeny-related changes in proliferative potential of human hematopoietic cells.
Lansdorp, P. M., Dragowska, W. H., & Mayani, H. (1993) · The Journal of Experimental Medicine · doi:10.1084/jem.178.3.787 · Cited by 384 · see citing works
Self-citationActivation of telomerase in a human tumor.
de Lange, T. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.8.2882 · Cited by 282 · see citing works
Harrison, D. E., & Astle, C. M. (1982) · The Journal of Experimental Medicine · doi:10.1084/jem.156.6.1767 · Cited by 281 · see citing works
Lansdorp, P., & Dragowska, W. H. (1992) · The Journal of Experimental Medicine · doi:10.1084/jem.175.6.1501 · Cited by 223 · see citing works
Self-citationLife span of multipotential hematopoietic stem cells in vivo.
Keller, G. M., & Snodgrass, R. (1990) · The Journal of Experimental Medicine · doi:10.1084/jem.171.5.1407 · Cited by 216 · see citing works
ORGANIZATION OF HAEMOPOIETIC STEM CELLS: THE GENERATION‐AGE HYPOTHESIS
Rosendaal, M., HODGSON, G. S., & Bradley, T. R. (1979) · Cell Proliferation · doi:10.1111/j.1365-2184.1979.tb00110.x · Cited by 176 · see citing works
Snodgrass, R., & Keller, G. M. (1987) · The EMBO Journal · doi:10.1002/j.1460-2075.1987.tb02737.x · Cited by 165 · see citing works
Ross, E., Anderson, N., & Micklem, H. S. (1982) · The Journal of Experimental Medicine · doi:10.1084/jem.155.2.432 · Cited by 137 · see citing works
Mayani, H., Dragowska, W. H., & Lansdorp, P. (1993) · Blood · doi:10.1182/blood.v81.12.3252.3252 · Cited by 110 · see citing works
Self-citationMintz, B., Anthony, K., & Litwin, S. (1984) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.81.24.7835 · Cited by 110 · see citing works
Capel, B., Hawley, R. G., Covarrubias, L., Hawley, T. S., & Mintz, B. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.12.4564 · Cited by 107 · see citing works
Expansion in vitro of retrovirally marked totipotent hematopoietic stem cells
Fraser, C., Eaves, C. J., Szilvassy, S. J., & Humphries, R. K. (1990) · Blood · doi:10.1182/blood.v76.6.1071.1071 · Cited by 101 · see citing works
Hornung, R., & Longo, D. (1992) · Blood · doi:10.1182/blood.v80.1.77.77 · Cited by 94 · see citing works
Significant telomere shortening in childhood leukemia
Adamson, D. J. A., King, D. J., & Kingsbury, N. (1992) · Cancer Genetics and Cytogenetics · doi:10.1016/0165-4608(92)90088-p · Cited by 68 · see citing works
Development of adult bone marrow stem cells in H-2-compatible and -incompatible mouse fetuses.
Fleischman, R. A., & Mintz, B. (1984) · The Journal of Experimental Medicine · doi:10.1084/jem.159.3.731 · Cited by 68 · see citing works
Mauch, P., Down, J. D., WARHOL, M., & HELLMEN, S. (1988) · Transplantation · doi:10.1097/00007890-198808000-00004 · Cited by 41 · see citing works
Aging, healing, and the metabolism of telomeres.
Broccoli, D., & Cooke, H. J. (1993) · Europe PMC (PubMed Central) · Cited by 19 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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 · see citing works
Self-citationThe RNA Component of Human Telomerase
Feng, J., Funk, W. D., Wang, S.-S., Weinrich, S. L., Avilion, A. A., Chiu, C.-P., Adams, R. R., Chang, E., Allsopp, R. C., Yu, J., et al. (1995) · Science · doi:10.1126/science.7544491 · Cited by 2,227 · see citing works
Self-citationWeissman, I. L. (2000) · Cell · doi:10.1016/s0092-8674(00)81692-x · Cited by 1,827 · see citing works
Amit, M., Carpenter, M. K., Inokuma, M. S., Chiu, C., Harris, C. P., Waknitz, M. A., Itskovitz‐Eldor, J., & Thomson, J. A. (2000) · Developmental Biology · doi:10.1006/dbio.2000.9912 · Cited by 1,471 · see citing works
Telomerase Mutations in Families with Idiopathic Pulmonary Fibrosis
Armanios, M. Y., Chen, J. J.-L., Cogan, J. D., Alder, J. K., Ingersoll, R. G., Markin, C., Lawson, W. E., Xie, M., Vulto, I., Phillips, J. A., et al. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa066157 · Cited by 1,357 · see citing works
Self-citationLongevity, 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
Outcome of Cord-Blood Transplantation from Related and Unrelated Donors
Gluckman, É., Rocha, V., Boyer-Chammard, A., Locatelli, F., Arcese, W., Pasqüini, R., Ortega, J., Souillet, G., Ferreira, E., Laporte, J. P., et al. (1997) · New England Journal of Medicine · doi:10.1056/nejm199708073370602 · Cited by 1,247 · see citing works
Aubert, G., & Lansdorp, P. M. (2008) · Physiological Reviews · doi:10.1152/physrev.00026.2007 · Cited by 1,188 · see citing works
Self-citationRegulatory Mechanisms in Stem Cell Biology
Morrison, S. J., Shah, N. M., & Anderson, D. J. (1997) · Cell · doi:10.1016/s0092-8674(00)81867-x · Cited by 1,040 · see citing works
Kögler, G., Sensken, S., Airey, J. A., Trapp, T., Müschen, M., Feldhahn, N., Liedtke, S., Sorg, R. V., Fischer, J., Rosenbaum, C., et al. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20040440 · Cited by 1,029 · see citing works
Armanios, M., & Blackburn, E. H. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3246 · Cited by 982 · see citing works
Stems Cells and the Pathways to Aging and Cancer
Rossi, D. J., Jamieson, C. H. M., & Weissman, I. L. (2008) · Cell · doi:10.1016/j.cell.2008.01.036 · Cited by 895 · see citing works
The aging of the immune system
Weiskopf, D., Weinberger, B., & Grubeck-Loebenstein, B. (2009) · Transplant International · doi:10.1111/j.1432-2277.2009.00927.x · Cited by 908 · see citing works
Transplanted cord blood–derived endothelial precursor cells augment postnatal neovascularization
Murohara, T., Ikeda, H., Duan, J., Shintani, S., Sasaki, K., Eguchi, H., Onitsuka, I., Matsui, K., & Imaizumi, T. (2000) · Journal of Clinical Investigation · doi:10.1172/jci8296 · Cited by 892 · see citing works
Heterogeneity 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
Self-citationThe aging of hematopoietic stem cells
Morrison, S. J., Wandycz, A. M., Akashi, K., Globerson, A., & Weissman, I. L. (1996) · Nature Medicine · doi:10.1038/nm0996-1011 · Cited by 853 · see citing works
Calado, R. T., & Young, N. S. (2009) · New England Journal of Medicine · doi:10.1056/nejmra0903373 · Cited by 783 · see citing works
The Biology of Hematopoietic Stem Cells
Morrison, S. J., Uchida, N., & Weissman, I. L. (1995) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cb.11.110195.000343 · Cited by 774 · see citing works
Telomerase activity in normal and malignant hematopoietic cells.
Broccoli, D., Young, J. W., & de Lange, T. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.20.9082 · Cited by 752 · see citing works
Telomere length, stem cells and aging
Blasco, M. A. (2007) · Nature Chemical Biology · doi:10.1038/nchembio.2007.38 · Cited by 747 · see citing works
Brouilette, S., Moore, J. S., McMahon, A. D., Thompson, J. R., Ford, I., Shepherd, J., Packard, C. J., & Samani, N. J. (2007) · The Lancet · doi:10.1016/s0140-6736(07)60071-3 · Cited by 744 · see citing works
Telomere length in early life predicts lifespan
Heidinger, B. J., Blount, J. D., Boner, W., Griffiths, K., Metcalfe, N. B., & Monaghan, P. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1113306109 · Cited by 713 · see citing works
Transcription Factors, Normal Myeloid Development, and Leukemia
Tenen, D. G., Hromas, R., Licht, J. D., & Zhang, D.-E. (1997) · Blood · doi:10.1182/blood.v90.2.489 · Cited by 735 · see citing works
Telomerase and cancer therapeutics
Harley, C. B. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2275 · Cited by 728 · see citing works
Self-citationAge-Associated Characteristics of Murine Hematopoietic Stem Cells
Sudo, K., Ema, H., Morita, Y., & Nakauchi, H. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.192.9.1273 · Cited by 722 · see citing works
Rufer, N., Brümmendorf, T. H., Kolvraa, S., Bischoff, C., Christensen, K., Wadsworth, L., Schulzer, M., & Lansdorp, P. M. (1999) · The Journal of Experimental Medicine · doi:10.1084/jem.190.2.157 · Cited by 709 · see citing works
Self-citationPassegue, E. A., Jamieson, C. H. M., Ailles, L., & Weissman, I. L. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2034201100 · Cited by 685 · see citing works
Telomere shortening in atherosclerosis
Samani, N. J., Boultby, R., Butler, R., Thompson, J. R., & Goodall, A. H. (2001) · The Lancet · doi:10.1016/s0140-6736(01)05633-1 · Cited by 609 · see citing works
Mechanisms of Stem Cell Self-Renewal
He, S., Nakada, D., & Morrison, S. J. (2009) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.042308.113248 · Cited by 607 · see citing works
Telomerase activity in normal leukocytes and in hematologic malignancies
Counter, C. M., Gupta, J., Harley, C., Leber, B. F., & Bacchetti, S. (1995) · Blood · doi:10.1182/blood.v85.9.2315.bloodjournal8592315 · Cited by 604 · see citing works
Self-citationTelomerase in the human organism
Collins, K., & Mitchell, J. R. (2002) · Oncogene · doi:10.1038/sj.onc.1205083 · Cited by 600 · see citing works
White Cell Telomere Length and Risk of Premature Myocardial Infarction
Brouilette, S., Singh, R. K., Thompson, J. R., Goodall, A. H., & Samani, N. J. (2003) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.0000067426.96344.32 · Cited by 590 · see citing works
Telomere length assessment: Biomarker of chronic oxidative stress?
Houben, J. M. J., Moonen, H. J. J., van Schooten, F., & Hageman, G. J. (2007) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2007.10.001 · Cited by 562 · 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
Self-citationTelomere Length in Epidemiology: A Biomarker of Aging, Age-Related Disease, Both, or Neither?
Sanders, J. L., & Newman, A. B. (2013) · Epidemiologic Reviews · doi:10.1093/epirev/mxs008 · Cited by 541 · see citing works
Clonal dynamics of haematopoiesis across the human lifespan
Mitchell, E., Chapman, M. S., Williams, N., Dawson, K. J., Mende, N., Calderbank, E. F., Jung, H., Mitchell, T. J., Coorens, T. H. H., Spencer, D. H., et al. (2022) · Nature · doi:10.1038/s41586-022-04786-y · Cited by 500 · see citing works
Telomeres in the mouse have large inter-chromosomal variations in the number of T 2 AG 3 repeats
Zijlmans, J. M. J. M., Martens, U. M., Poon, S. S. S., Raap, A. K., Tanke, H. J., Ward, R. K., & Lansdorp, P. M. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.14.7423 · Cited by 501 · see citing works
Self-citationAging and Replicative Senescence Have Related Effects on Human Stem and Progenitor Cells
Wagner, W., Bork, S., Horn, P., Krunic, D., Walenda, T., Diehlmann, A., Beneš, V., Blake, J., Huber, F.-X., Eckstein, V., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0005846 · Cited by 480 · see citing works
Human telomerase contains evolutionarily conserved catalytic and structural subunits
Harrington, L., Zhou, W., McPhail, T., Oulton, R., Yeung, D. S. K., Mar, V., Bass, M. B., & Robinson, M. O. (1997) · Genes & Development · doi:10.1101/gad.11.23.3109 · Cited by 465 · see citing works
Myocyte renewal and ventricular remodelling
Anversa, P., & Nadal‐Ginard, B. (2002) · Nature · doi:10.1038/415240a · Cited by 464 · see citing works
The immune system and aging: A review
Castelo-Branco, C., & Soveral, I. (2014) · Gynecological Endocrinology · doi:10.3109/09513590.2013.852531 · Cited by 449 · see citing works
Aging of hematopoietic stem cells
de Haan, G., & Lazare, S. S. (2018) · Blood · doi:10.1182/blood-2017-06-746412 · Cited by 432 · see citing works
Human naive and memory T lymphocytes differ in telomeric length and replicative potential.
Weng, N., Levine, B. L., June, C. H., & Hodes, R. J. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.24.11091 · Cited by 418 · see citing works
Regulated 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
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
Self-citationChimenti, C., Kajstura, J., Torella, D., Urbanek, K., Heleniak, H., Colussi, C., Di Meglio, F., Nadal-Ginard, B., Frustaci, A., Leri, A., et al. (2003) · Circulation Research · doi:10.1161/01.res.0000093985.76901.af · Cited by 386 · 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
Short telomeres on human chromosome 17p
Martens, U. M., Zijlmans, J. M. J. M., Poon, S. S. S., Dragowska, W., Yui, J., Chavez, E. A., Ward, R. K., & Lansdorp, P. M. (1998) · Nature Genetics · doi:10.1038/ng0198-018 · Cited by 393 · 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-citationT cells and aging january 2002 update
Pawelec, G. (2002) · Frontiers in bioscience · doi:10.2741/a831 · Cited by 368 · see citing works
Alter, B. P., Baerlocher, G. M., Savage, S. A., Chanock, S. J., Weksler, B. B., Willner, J. P., Peters, J. A., Giri, N., & Lansdorp, P. M. (2007) · Blood · doi:10.1182/blood-2007-02-075598 · Cited by 356 · see citing works
Self-citationPawelec, G. (1998) · Frontiers in bioscience · doi:10.2741/a266 · Cited by 357 · 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
Telomeres and age-related disease: how telomere biology informs clinical paradigms
Armanios, M. Y. (2013) · Journal of Clinical Investigation · doi:10.1172/jci66370 · Cited by 346 · see citing works
Stem 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
The power of exercise: buffering the effect of chronic stress on telomere length
Puterman, E., Lin, J., Blackburn, E., O'Donovan, A., Adler, N., & Epel, E. (2010) · PLoS ONE · doi:10.1371/journal.pone.0010837 · Cited by 339 · see citing works
Allsopp, R. C., Morin, G. B., DePinho, R., Harley, C. B., & Weissman, I. L. (2003) · Blood · doi:10.1182/blood-2002-07-2334 · Cited by 324 · see citing works
Self-citationTelomere length in different tissues of elderly patients
Friedrich, U., Griese, E.-U., Schwab, M., Fritz, P., Thon, K.-P., & Klotz, U. (2000) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(00)00173-1 · Cited by 325 · see citing works
Telomeres and telomerase in aging and cancer
Harley, C. (1995) · Current Opinion in Genetics & Development · doi:10.1016/0959-437x(95)80016-6 · Cited by 325 · see citing works
Self-citationMechanisms that Regulate Stem Cell Aging and Life Span
Signer, R. A. J., & Morrison, S. J. (2013) · Cell Stem Cell · doi:10.1016/j.stem.2013.01.001 · Cited by 320 · see citing works
Syndromes of Telomere Shortening
Armanios, M. (2009) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-082908-150046 · Cited by 317 · see citing works
Expansion of mesenchymal stem cells isolated from pediatric and adult donor bone marrow
Mareschi, K., Ferrero, I., Rustichelli, D., Aschero, S., Gammaitoni, L., Aglietta, M., Madon, E., & Fagioli, F. (2005) · Journal of Cellular Biochemistry · doi:10.1002/jcb.20681 · Cited by 319 · 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
Ageing of lymphocytes and lymphocytes in the aged
Globerson, A., & Effros, R. B. (2000) · Immunology Today · doi:10.1016/s0167-5699(00)01714-x · Cited by 309 · see citing works
The 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
de Haan, G., NIJHOF, W., & Zant, G. E. V. (1997) · Blood · doi:10.1182/blood.v89.5.1543 · Cited by 300 · 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
Changes in primary lymphoid organs with aging
Chinn, I. K., Blackburn, C. C., Manley, N. R., & Sempowski, G. D. (2012) · Seminars in Immunology · doi:10.1016/j.smim.2012.04.005 · Cited by 282 · see citing works
Telomeres shorten more slowly in long-lived birds and mammals than in short–lived ones
Haussmann, M. F., Winkler, D. W., O'Reilly, K. M., Huntington, C. E., Nisbet, I. C. T., & Vleck, C. M. (2003) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.2003.2385 · Cited by 290 · 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
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
Life histories of myeloproliferative neoplasms inferred from phylogenies
Williams, N., Lee, J., Mitchell, E., Moore, L., Baxter, E. J., Hewinson, J., Dawson, K. J., Menzies, A., Godfrey, A. L., Green, A. R., et al. (2022) · Nature · doi:10.1038/s41586-021-04312-6 · Cited by 285 · see citing works
Telomere Length of Circulating Leukocytes Is Decreased in Patients With Chronic Heart Failure
van der Harst, P., van der Steege, G., de Boer, R. A., Voors, A. A., Hall, A. S., Mulder, M. J., van Gilst, W. H., & van Veldhuisen, D. J. (2007) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2007.01.027 · Cited by 281 · see citing works
Branche, H. L., Dupuis, S., Ben‐David, Y., Bani, M. R., Wellinger, R. J., & Chabot, B. (1998) · Nature Genetics · doi:10.1038/575 · Cited by 280 · see citing works
Telomere biology in healthy aging and disease
Oeseburg, H., de Boer, R. A., van Gilst, W. H., & van der Harst, P. (2009) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-009-0728-1 · Cited by 273 · see citing works
Telomere 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
Clonal heterogeneity in differentiation potential of immortalized human mesenchymal stem cells
Okamoto, T., Aoyama, T., Nakayama, T., Nakamata, T., Hosaka, T., Nishijo, K., Nakamura, T., Kiyono, T., & Toguchida, J. (2002) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(02)00661-7 · Cited by 267 · 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
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
Self-citationThe heterochromatin loss model of aging
Villeponteau, B. (1997) · Experimental Gerontology · doi:10.1016/s0531-5565(96)00155-6 · Cited by 261 · see citing works
The replication rate of human hematopoietic stem cells in vivo
Catlin, S. N., Busque, L., Gale, R. E., Guttorp, P., & Abkowitz, J. L. (2011) · Blood · doi:10.1182/blood-2010-08-303537 · Cited by 259 · see citing works
Aubert, G., Baerlocher, G. M., Vulto, I. M., Poon, S. S. S., & Lansdorp, P. M. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1002696 · Cited by 257 · see citing works
Self-citationMarciniak-Czochra, A. K., Stiehl, T., Ho, A. D., Jäger, W., & Wagner, W. (2008) · Stem Cells and Development · doi:10.1089/scd.2008.0143 · Cited by 255 · 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
Kèlland, L. R. (2005) · European Journal of Cancer · doi:10.1016/j.ejca.2004.11.024 · Cited by 253 · see citing works
Telomere loss in relation to age and early environment in long-lived birds
Hall, M. E., Nasir, L., Daunt, F., Gault, E. A., Croxall, J. P., Wanless, S., & Monaghan, P. (2004) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.2004.2768 · Cited by 247 · see citing works
Biology of Human Umbilical Cord Blood‐Derived Hematopoietic Stem/Progenitor Cells
Mayani, H., & Lansdorp, P. M. (1998) · Stem Cells · doi:10.1002/stem.160153 · Cited by 246 · see citing works
Self-citationRegulation of Reactive Oxygen Species and Genomic Stability in Hematopoietic Stem Cells
Naka, K., Muraguchi, T., Hoshii, T., & Hirao, A. (2008) · Antioxidants and Redox Signaling · doi:10.1089/ars.2008.2114 · Cited by 244 · see citing works
Quantifying T lymphocyte turnover
de Boer, R. J., & Perelson, A. S. (2013) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2012.12.025 · Cited by 241 · see citing works
Cellular Senescence: Molecular Mechanisms, In Vivo Significance, and Redox Considerations
Müller, M. K. (2008) · Antioxidants and Redox Signaling · doi:10.1089/ars.2008.2104 · Cited by 237 · see citing works
Telomerase regulation and stem cell behaviour
Flores, I., Benetti, R., & Blasco, M. A. (2006) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2006.03.003 · Cited by 232 · see citing works
The aging of lympho-hematopoietic stem cells
Geiger, H., & Van Zant, G. (2002) · Nature Immunology · doi:10.1038/ni0402-329 · Cited by 233 · see citing works
Telomere length in leukocyte subpopulations of patients with aplastic anemia
Brümmendorf, T. H., Maciejewski, J. P., Mak, J., Young, N. S., & Lansdorp, P. M. (2001) · Blood · doi:10.1182/blood.v97.4.895 · Cited by 233 · see citing works
Self-citationEstrada, J. C., Torres, Y., Benguría, A., Dopazo, A., Roche, E., Carrera-Quintanar, L., Acín‐Pérez, R., Enrı́quez, J. A., Torres-Ruiz, R., Ramírez, J. C., et al. (2013) · Cell Death and Disease · doi:10.1038/cddis.2013.211 · Cited by 229 · see citing works
Paternal age is positively linked to telomere length of children
Unryn, B. M., Cook, L. S., & Riabowol, K. T. (2005) · Aging Cell · doi:10.1111/j.1474-9728.2005.00144.x · Cited by 224 · see citing works
Accelerated telomere shortening in young recipients of allogeneic bone-marrow transplants
Wynn, R. F., Cross, M. A., Hatton, C. E., Will, A., Lashford, L. S., Dexter, T. M., & Testa, N. G. (1998) · The Lancet · doi:10.1016/s0140-6736(97)08256-1 · Cited by 228 · see citing works
Vulliamy, T., Knight, S. W., Mason, P. J., & Dokal, I. S. (2001) · Blood Cells Molecules and Diseases · doi:10.1006/bcmd.2001.0389 · Cited by 224 · see citing works
Chance or necessity? Insertional Mutagenesis in Gene Therapy and Its Consequences
Baum, C., Kalle, C. V., Staal, F. J. T., Li, Z., Fehse, B., Schmidt, M., Weerkamp, F., Karlsson, S., Wagemaker, G., & Williams, D. A. (2004) · Molecular Therapy · doi:10.1016/j.ymthe.2003.10.013 · Cited by 225 · see citing works
- Authors
- Vaziri, H., Dragowska, W., Allsopp, R. C., Thomas, T. E., Harley, C. B., & Lansdorp, P. M.
- Affiliations
- Geron (United States) (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1994-10-11
- Volume
- 91
- Issue
- 21
- Pages
- 9857-9860
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC44916
- OpenAlex
- W2068409711
- Cited by
- 1,132
- References
- 41
- Citations by year
- 2026: 7 · 2025: 12 · 2024: 5 · 2023: 11 · 2022: 22 · 2021: 14 · 2020: 31 · 2019: 22 · 2018: 20 · 2017: 24 · 2016: 20 · 2015: 29 · 2014: 36 · 2013: 40 · 2012: 39
- FWCI
- 26.07
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG09383A)
- National Institute of Allergy and Infectious Diseases (AI 29524)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- hematopoietic stem cells, telomere length, cellular senescence, stem cell aging, bone marrow, fetal liver, umbilical cord blood, hematopoiesis, gene therapy
- MeSH terms
- Adolescent, Adult, Aging, Bone Marrow, DNA, Fetal Blood, Fetus, Hematopoietic Stem Cells, Humans, Liver, Middle Aged, Mitosis, Antigens, CD, Telomere
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