Telomere length predicts replicative capacity of human fibroblasts.
Open accessAbstract
When human fibroblasts from different donors are grown in vitro, only a small fraction of the variation in their finite replicative capacity is explained by the chronological age of the donor. Because we had previously shown that telomeres, the terminal guanine-rich sequences of chromosomes, shorten throughout the life-span of cultured cells, we wished to determine whether variation in initial telomere length would account for the unexplained variation in replicative capacity. Analysis of cells from 31 donors (aged 0-93 yr) indicated relatively weak correlations between proliferative ability and donor age (m = -0.2 doubling per yr; r = -0.42; P = 0.02) and between telomeric DNA and donor age (m = -15 base pairs per yr; r = -0.43; P = 0.02). However, there was a striking correlation, valid over the entire age range of the donors, between replicative capacity and initial telomere length (m = 10 doublings per kilobase pair; r = 0.76; P = 0.004), indicating that cell strains with shorter telomeres underwent significantly fewer doublings than those with longer telomeres. These observations suggest that telomere length is a biomarker of somatic cell aging in humans and are consistent with a causal role for telomere loss in this process. We also found that fibroblasts from Hutchinson-Gilford progeria donors had short telomeres, consistent with their reduced division potential in vitro. In contrast, telomeres from sperm DNA did not decrease with age of the donor, suggesting that a mechanism for maintaining telomere length, such as telomerase expression, may be active in germ-line tissue.
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Human male germ cells maintain stable telomere lengths or even lengthen them with age.
“In human male germ cells, telomere lengths remain stable or even elongate with age3.”
From The telomere syndromes (2012) · cites this paper as [3]
A total lifetime loss of approximately 2-4 kb in average telomere length has been observed in human cells.
“A total lifetime loss of ~2-4 kb in average telomere length has been observed in human cells8-10.”
From Telomere dysfunction and tumour suppression: the senescence connection (2008) · cites this paper as [9]
Telomere attrition gradually appears with increasing number of cell divisions, triggering replicative senescence.
“As a consequence, telomere attrition gradually appears with increasing number of cell divisions, triggering replicative senescence [2, 48].”
From Senescence-related impairment of autophagy induces toxic intraneuronal amyloid-β accumulation in a mouse model of amyloid pathology (2023) · cites this paper as [2]
Telomere length has been shown to predict the replicative capacity of human cells and the appearance of certain age-associated pathologies in humans.
“telomere length has been shown to predict the replicative capacity of human cells and the appearance of certain age-associated pathologies in humans 54, 55”
From The common biology of cancer and ageing (2007) · cites this paper as [54]
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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
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
Self-citationMoyzis, 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
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 · 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
WATSON, J. D. (1972) · Nature New Biology · doi:10.1038/newbio239197a0 · Cited by 1,632 · see citing works
THE STABILITY OF BROKEN ENDS OF CHROMOSOMES IN ZEA MAYS
McClintock, B. (1941) · Genetics · doi:10.1093/genetics/26.2.234 · Cited by 1,610 · see citing works
Yeast transformation: a model system for the study of recombination.
Orr‐Weaver, T. L., Szostak, J. W., & Rothstein, R. J. (1981) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.78.10.6354 · Cited by 1,501 · see citing works
Morin, G. B. (1989) · Cell · doi:10.1016/0092-8674(89)90035-4 · Cited by 1,495 · 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-citationTelomere end-replication problem and cell aging
Levy, M. Z., Allsopp, R. C., Futcher, A. B., Greider, C. W., & Harley, C. B. (1992) · Journal of Molecular Biology · doi:10.1016/0022-2836(92)90096-3 · Cited by 1,069 · see citing works
Self-citationReplicative life-span of cultivated human cells. Effects of donor's age, tissue, and genotype.
Gm, M., Sprague, C. A., & Cj, E. (1970) · PubMed · Cited by 1,003 · 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
Deininger, P. L. (1991) · Analytical Biochemistry · doi:10.1016/0003-2697(91)90283-y · Cited by 893 · see citing works
Replicative Senescence: the Human Fibroblast Comes of Age
Goldstein, S. (1990) · Science · doi:10.1126/science.2204114 · Cited by 651 · see citing works
Self-citationHypervariable ultra-long telomeres in mice
Kipling, D., & Cooke, H. J. (1990) · Nature · doi:10.1038/347400a0 · Cited by 614 · see citing works
Wright, W. E., Pereira‐Smith, O. M., & Shay, J. W. (1989) · Molecular and Cellular Biology · doi:10.1128/mcb.9.7.3088 · Cited by 478 · see citing works
In 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
Three-dimensional architecture of a polytene nucleus
Agard, D. A., & Sedat, J. W. (1983) · Nature · doi:10.1038/302676a0 · Cited by 443 · see citing works
Human telomeres contain at least three types of G–rich repeat distributed non-randomly
Allshire, R. C., Dempster, M., & Hastie, N. D. (1989) · Nucleic Acids Research · doi:10.1093/nar/17.12.4611 · Cited by 372 · see citing works
Pereira‐Smith, O. M., & Smith, J. R. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.16.6042 · Cited by 355 · see citing works
Röhme, D. (1981) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.78.8.5009 · Cited by 351 · see citing works
Human telomeres are attached to the nuclear matrix.
de Lange, T. (1992) · The EMBO Journal · doi:10.1002/j.1460-2075.1992.tb05104.x · Cited by 333 · see citing works
Evidence for the Recessive Nature of Cellular Immortality
Pereira‐Smith, O. M., & Smith, J. R. (1983) · Science · doi:10.1126/science.6879195 · Cited by 286 · see citing works
Telomeres, telomerase and senescence
Greider, C. W. (1990) · BioEssays · doi:10.1002/bies.950120803 · Cited by 262 · see citing works
Self-citationVariability at the Telomeres of the Human X/Y Pseudoautosomal Region
Cooke, H. J., & Smith, B. A. (1986) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.1986.051.01.026 · Cited by 233 · see citing works
Defining cellular senescence in IMR-90 cells: a flow cytometric analysis.
Sherwood, S. W., Rush, D. F., Ellsworth, J. L., & SCHIMKE, R. T. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.23.9086 · Cited by 200 · see citing works
ANEUPLOIDY IN THE DEGENERATIVE PHASE OF SERIAL CULTIVATION OF HUMAN CELL STRAINS
SAKSELA, E., & Moorhead, P. S. (1963) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.50.2.390 · Cited by 192 · see citing works
Goldstein, S., Moerman, E. J., Soeldner, J. S., Gleason, R. E., & Barnett, D. M. (1978) · Science · doi:10.1126/science.622567 · Cited by 190 · see citing works
Self-citationExtensive telomere repeat arrays in mouse are hypervariable
Starling, J., Maule, J., Hastie, N. D., & Allshire, R. C. (1990) · Nucleic Acids Research · doi:10.1093/nar/18.23.6881 · Cited by 173 · see citing works
Cellular Senescence revisited: a review
Stanulis-Praeger, B. (1987) · Mechanisms of Ageing and Development · doi:10.1016/0047-6374(87)90109-6 · Cited by 171 · see citing works
Specific chromosome aberrations in senescent fibroblast cell lines derived from human embryos.
Pa, B. (1976) · PubMed · Cited by 168 · see citing works
Viable deletions of a telomere from a Drosophila chromosome
Levis, R. W. (1989) · Cell · doi:10.1016/0092-8674(89)90112-8 · Cited by 167 · see citing works
Chromosome ends in Drosophila without telomeric DNA sequences.
Biessmann, H., Carter, S. B., & Mason, J. M. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.5.1758 · Cited by 137 · see citing works
Reversible Cellular Senescence: Implications for Immortalization of Normal Human Diploid Fibroblasts
Wright, W. E., Pereira‐Smith, O. M., & Shay, J. W. (1989) · Molecular and Cellular Biology · doi:10.1128/mcb.9.7.3088-3092.1989 · Cited by 136 · see citing works
HEALING OF BROKEN LINEAR DICENTRIC CHROMOSOMES IN YEAST
Haber, J. E., & Thorburn, P. C. (1984) · Genetics · doi:10.1093/genetics/106.2.207 · Cited by 124 · see citing works
Progressive loss of DNA sequences from terminal chromosome deficiencies in Drosophila melanogaster.
Biessmann, H., & Mason, J. M. (1988) · The EMBO Journal · doi:10.1002/j.1460-2075.1988.tb02916.x · Cited by 116 · see citing works
Goldstein, S. (1974) · Experimental Cell Research · doi:10.1016/0014-4827(74)90342-5 · Cited by 91 · see citing works
Self-citationMather, M. W. (1988) · PubMed · Cited by 28 · see citing works
The role of limited cell replicative capacity in pathological age change. A review
Walton, J. R. (1982) · Mechanisms of Ageing and Development · doi:10.1016/0047-6374(82)90056-2 · Cited by 22 · see citing works
Does Progeria Provide the Best Model of Accelerated Ageing in Humans?
Mills, R. G., & Weiss, A. S. (2009) · Gerontology · doi:10.1159/000213181 · Cited by 13 · see citing works
Flagged first, then by citations
Research works printed but not linked: 9
- [5]Rohme, D. (1981) Proc. Natl. Acad. Sci. USA 78, 5009–5013.
- [15]Orr-Weaver, T. L., Szostak, & Rothstein, R. J. (1981) Proc. Natl. Acad. Sci. USA 78, 6354–6358.
- [18]Moyzis, R. K., Buckingham, J. M., Cram, L. S., Dani, M., Deaven, L. L., Jones, M. D., Meyne, J., Ratliff, R. L. & Wu, J.-R. (1988) Proc. Natl. Acad. Sci. USA 85, 6622–6626.
- [27]Saksela, E. & Moorhead, P. S. (1963) Proc. Natl. Acad. Sci. USA 50, 390–395.
- [29]Sherwood, S. W., Rush, D., Ellsworth, J. L. & Schimke, R. T. (1989) Proc. Natl. Acad. Sci. USA 85, 9086–9090.
- [34]Goldstein, S. (1978) in Genetics of Aging, ed. Schneider, E. L. (Plenum, New York), pp. 171–224.
- [43]Biessmann, H., Carter, S. B. & Mason, J. M. (1990) Proc. Natl. Acad. Sci. USA 87, 1758–1761.
- [45]Norwood, T., Smith, J. R. & Stein, G. H. (1990) in Handbook of the Biology of Aging, eds. Schneider, E. L. & Rowe, J. W. (Academic, San Diego), pp. 131–156.
- [47]Pereira-Smith, O. M. & Smith, J. R. (1988) Proc. Natl. Acad. Sci. USA 85, 6042–6046.
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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-citationExtension 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
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-citationTelomere Shortening and Tumor Formation by Mouse Cells Lacking Telomerase RNA
Blasco, M. A., Lee, H.-W., Hande, M. P., Samper, E., Lansdorp, P. M., DePinho, R. A., & Greider, C. W. (1997) · Cell · doi:10.1016/s0092-8674(01)80006-4 · Cited by 2,108 · see citing works
Self-citationTRF2 Protects Human Telomeres from End-to-End Fusions
van Steensel, B., Smogorzewska, A., & de Lange, T. (1998) · Cell · doi:10.1016/s0092-8674(00)80932-0 · Cited by 1,709 · 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
Self-citationTelomere elongation in immortal human cells without detectable telomerase activity
Bryan, T. M., Englezou, A., Gupta, J., Bacchetti, S., & Reddel, R. R. (1995) · The EMBO Journal · doi:10.1002/j.1460-2075.1995.tb00098.x · Cited by 1,279 · see citing works
Hemann, M. T., Strong, M. A., Hao, L.-Y., & Greider, C. W. (2001) · Cell · doi:10.1016/s0092-8674(01)00504-9 · Cited by 1,219 · see citing works
Self-citationDi Leonardo, A., Linke, S. P., Clarkin, K., & Wahl, G. M. (1994) · Genes & Development · doi:10.1101/gad.8.21.2540 · Cited by 1,215 · see citing works
Kiyono, T., Foster, S. A., Koop, J. I., McDougall, J. K., Galloway, D. A., & Klingelhutz, A. J. (1998) · Nature · doi:10.1038/23962 · Cited by 1,206 · see citing works
Aubert, G., & Lansdorp, P. M. (2008) · Physiological Reviews · doi:10.1152/physrev.00026.2007 · Cited by 1,188 · see citing works
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Vaziri, H., Dragowska, W., Allsopp, R. C., Thomas, T. E., Harley, C. B., & Lansdorp, P. M. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.21.9857 · Cited by 1,132 · see citing works
Self-citationVaziri, H., & Benchimol, S. (1998) · Current Biology · doi:10.1016/s0960-9822(98)70109-5 · Cited by 1,003 · see citing works
Self-citationThe common biology of cancer and ageing
Finkel, T., Serrano, M., & Blasco, M. A. (2007) · Nature · doi:10.1038/nature05985 · Cited by 988 · see citing works
Armanios, M., & Blackburn, E. H. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3246 · Cited by 982 · see citing works
DePinho, R. A. (2000) · Nature · doi:10.1038/35041694 · Cited by 951 · see citing works
Identification of seven loci affecting mean telomere length and their association with disease
CARDIoGRAM consortium, Codd, V., Nelson, C. P., Albrecht, E., Mangino, M., Deelen, J., Buxton, J. L., Hottenga, J. J., Fischer, K., Esko, T., et al. (2013) · Nature Genetics · doi:10.1038/ng.2528 · Cited by 933 · see citing works
Unmasking senescence: context-dependent effects of SASP in cancer
Faget, D. V., Ren, Q., & Stewart, S. A. (2019) · Nature Reviews Cancer · doi:10.1038/s41568-019-0156-2 · Cited by 863 · see citing works
Measuring biological aging in humans: a quest
Ferrucci, L., Gonzalez‐Freire, M., Fabbri, E., Simonsick, E., Tanaka, T., Moore, Z., Salimi, S., Sierra, F., & de Cabo, R. (2020) · Aging Cell · doi:10.1111/acel.13080 · Cited by 781 · see citing works
<i>TLC1</i> : Template RNA Component of <i>Saccharomyces cerevisiae</i> Telomerase
Singer, M. S., & Gottschling, D. E. (1994) · Science · doi:10.1126/science.7545955 · Cited by 736 · 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
Telomerase 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-citationBiologic properties of mesenchymal stem cells derived from bone marrow and adipose tissue
Izadpanah, R., Trygg, C., Patel, B., Kriedt, C., Dufour, J., Gimble, J. M., & Bunnell, B. A. (2006) · Journal of Cellular Biochemistry · doi:10.1002/jcb.20904 · Cited by 670 · see citing works
Correlating telomerase activity levels with human neuroblastoma outcomes
Hiyama, E., Hiyama, K., Yokoyama, T., Matsuura, Y., Piatyszek, M. A., & Shay, J. W. (1995) · Nature Medicine · doi:10.1038/nm0395-249 · Cited by 611 · 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
Extensive allelic variation and ultrashort telomeres in senescent human cells
Baird, D. M., Rowson, J., Wynford-Thomas, D., & Kipling, D. (2003) · Nature Genetics · doi:10.1038/ng1084 · Cited by 570 · see citing works
Accumulation of senescent cells in Mitotic tissue of aging primates
Jeyapalan, J. C., Ferreira, M., Sedivy, J. M., & Herbig, U. (2007) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2006.11.008 · Cited by 571 · see citing works
Replicative Senescence: Implications for in Vivo Aging and Tumor Suppression
Smith, J. R., & Pereira-Smith, O. M. (1996) · Science · doi:10.1126/science.273.5271.63 · Cited by 547 · see citing works
Markers of cellular senescence. Telomere shortening as a marker of cellular senescence
Bernadotte, A., Mikhelson, V. M., & Spivak, I. M. (2016) · Aging · doi:10.18632/aging.100871 · Cited by 466 · 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
Armanios, M., Chen, J.-L., Chang, Y.-P. C., Brodsky, R. A., Hawkins, A., Griffin, C. A., Eshleman, J. R., Cohen, A. R., Chakravarti, A., Hamosh, A., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0508124102 · Cited by 452 · see citing works
Self-citationBroer, L., Codd, V., Nyholt, D. R., Deelen, J., Mangino, M., Willemsen, G., Albrecht, E., Amin, N., Beekman, M., de Geus, E. J. C., et al. (2013) · European Journal of Human Genetics · doi:10.1038/ejhg.2012.303 · Cited by 450 · see citing works
Geronimus, A. T., Hicken, M. T., Pearson, J. A., Seashols, S. J., Brown, K. L., & Cruz, T. D. (2010) · Human Nature · doi:10.1007/s12110-010-9078-0 · Cited by 447 · see citing works
Choudhury, A. R., Ju, Z., Djojosubroto, M. W., Schienke, A., Lechel, A., Schaetzlein, S., Jiang, H., Stepczynska, A., Wang, C., Buer, J., et al. (2007) · Nature Genetics · doi:10.1038/ng1937 · Cited by 426 · see citing works
Biomarkers of cellular senescence and skin aging
Wang, A. S., & Dreesen, O. (2018) · Frontiers in Genetics · doi:10.3389/fgene.2018.00247 · Cited by 404 · 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
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-citationTelomerase 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
Telomere length is paternally inherited and is associated with parental lifespan
Njajou, O. T., Cawthon, R. M., Damcott, C. M., Wu, S.-H., Ott, S., Garant, M. J., Blackburn, E. H., Mitchell, B. D., Shuldiner, A. R., & Hsueh, W.-C. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0702703104 · Cited by 387 · see citing works
Progeria syndromes and ageing: what is the connection?
Burtner, C. R., & Kennedy, B. K. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2944 · Cited by 386 · see citing works
Huang, L. C., Clarkin, K. C., & Wahl, G. M. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.10.4827 · Cited by 384 · see citing works
Kennedy, B. K., Gotta, M., Sinclair, D. A., Mills, K., McNabb, D. S., Murthy, M., Pak, S. M., Laroche, T., Gasser, S. M., & Guarente, L. (1997) · Cell · doi:10.1016/s0092-8674(00)80219-6 · Cited by 375 · see citing works
Shortened Telomere Length Is Associated with Increased Risk of Cancer: A Meta-Analysis
Ma, H., Zhou, Z., Wei, S., Liu, Z., Pooley, K. A., Dunning, A. M., Svenson, U., Roos, G., Hosgood, H. D., Shen, M., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0020466 · Cited by 376 · see citing works
“Thus, telomere length has been suggested as a ‘‘cellular mitotic clock’’ that defines the number of cell divisions and cellular life span [1,5].”
Is β-Galactosidase Staining a Marker of Senescence in Vitro and in Vivo?
Severino, J., Allen, R. G., Balin, S., Balin, A., & Cristofalo, V. J. (2000) · Experimental Cell Research · doi:10.1006/excr.2000.4875 · Cited by 370 · see citing works
In situ analyses of genome instability in breast cancer
Chin, K., de Solorzano, C. O., Knowles, D., Jones, A., Chou, W., Rodriguez, E. G., Kuo, W.-L., Ljung, B.-M., Chew, K., Myambo, K., et al. (2004) · Nature Genetics · doi:10.1038/ng1409 · Cited by 361 · see citing works
Counter, C. M., Botelho, F. M., Wang, P., Harley, C. B., & Bacchetti, S. (1994) · Journal of Virology · doi:10.1128/jvi.68.5.3410-3414.1994 · Cited by 355 · see citing works
Self-citationAubert, G., Hills, M., & Lansdorp, P. M. (2012) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2011.04.003 · Cited by 342 · see citing works
Clinical aspects and molecular diagnostics of skin aging
Zouboulis, C. C., & Makrantonaki, E. (2011) · Clinics in Dermatology · doi:10.1016/j.clindermatol.2010.07.001 · Cited by 341 · see citing works
Rheinwald, J. G., Hahn, W. C., Ramsey, M. R., Wu, J. Y., Guo, Z., Tsao, H., De Luca, M., Catricalà, C., & O'Toole, K. M. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.14.5157-5172.2002 · Cited by 338 · see citing works
Stress, cell senescence and organismal ageing
de Magalhães, J. P., & Passos, J. F. (2018) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2017.07.001 · Cited by 316 · see citing works
DNA damage and repair in telomeres: relation to aging
Kruk, P. A., Rampino, N. J., & Bohr, V. A. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.1.258 · Cited by 333 · see citing works
Telomere 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
Loss of transcriptional silencing causes sterility in old mother cells of S. cerevisiae
Smeal, T., Claus, J., Kennedy, B., Cole, F., & Guarente, L. (1996) · Cell · doi:10.1016/s0092-8674(00)81038-7 · Cited by 308 · 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
Cao, L., Li, W., Kim, S., Brodie, S. G., & Deng, C.-X. (2003) · Genes & Development · doi:10.1101/gad.1050003 · Cited by 293 · 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
Ogryzko, V. V., Hirai, T. H., Russanova, V. R., Barbie, D. A., & Howard, B. H. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.9.5210 · Cited by 268 · see citing works
Colonna-Romano, G., Bulati, M., Aquino, A., Pellicanò, M., Vitello, S., Lio, D., Candore, G., & Caruso, C. (2009) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2009.08.003 · Cited by 270 · 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
Mapping of a Major Locus that Determines Telomere Length in Humans
Vasa-Nicotera, M., Brouilette, S., Mangino, M., Thompson, J. R., Braund, P., Clemitson, J.-R., Mason, A., Bodycote, C. L., Raleigh, S. M., Louis, E., et al. (2005) · The American Journal of Human Genetics · doi:10.1086/426734 · Cited by 257 · see citing works
Zhu, Y., Liu, X., Ding, X., Wang, F., & Geng, X. (2019) · Biogerontology · doi:10.1007/s10522-018-9769-1 · Cited by 255 · see citing works
Cellular senescence in vivo: Its relevance in ageing and cardiovascular disease
Erusalimsky, J. D., & Kurz, D. J. (2005) · Experimental Gerontology · doi:10.1016/j.exger.2005.04.010 · Cited by 252 · 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
Yaar, M., Eller, M. S., & Gilchrest, B. A. (2002) · Journal of Investigative Dermatology Symposium Proceedings · doi:10.1046/j.1523-1747.2002.19636.x · Cited by 233 · see citing works
Schnabl, B., Purbeck, C. A., Choi, Y. H., Hagedorn, C. H., & Brenner, D. (2003) · Hepatology · doi:10.1053/jhep.2003.50097 · Cited by 224 · see citing works
McEachern, M. J., & Blackburn, E. H. (1996) · Genes & Development · doi:10.1101/gad.10.14.1822 · Cited by 224 · see citing works
Schulz, V. P., Zakian, V. A., Ogburn, C. E., McKay, J., Jarzebowicz, A. A., Martin, G. M., & Edland, S. D. (1996) · Human Genetics · doi:10.1007/bf02346184 · Cited by 221 · see citing works
Shortened telomere length in white blood cells of patients with IDDM.
Jeanclos, E., Krolewski, A., Skurnick, J., Kimura, M., Aviv, H., Warram, J. H., & Aviv, A. (1998) · Diabetes · doi:10.2337/diabetes.47.3.482 · Cited by 217 · see citing works
Schönland, S. O., Lopez, C., Widmann, T., Zimmer, J., Bryl, E., Goronzy, J. J., & Weyand, C. M. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2233561100 · Cited by 216 · 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
Dynamic Changes in Mouse Hematopoietic Stem Cell Numbers During Aging
de Haan, G., & Van Zant, G. (1999) · Blood · doi:10.1182/blood.v93.10.3294.410k07_3294_3301 · Cited by 208 · see citing works
Fibroblasts cultured from venous ulcers display cellular characteristics of senescence
Mendez, M. V., Stanley, A., Park, H.-Y., Shon, K., Phillips, T., & Menzoian, J. O. (1998) · Journal of Vascular Surgery · doi:10.1016/s0741-5214(98)70064-3 · Cited by 202 · see citing works
Telomeres and human aging: facts and fibs
Aviv, A. (2004) · Science of Aging Knowledge Environment · doi:10.1126/sageke.2004.51.pe43 · Cited by 198 · see citing works
Senescent cells: a therapeutic target for cardiovascular disease
Childs, B. G., Li, H., & van Deursen, J. M. (2018) · Journal of Clinical Investigation · doi:10.1172/jci95146 · Cited by 192 · 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
Shorter telomeres in dystrophic muscle consistent with extensive regeneration in young children
Decary, S., Ben Hamida, C., Mouly, V., Barbet, J. P., Hentati, F., & Butler-Browne, G. S. (2000) · Neuromuscular Disorders · doi:10.1016/s0960-8966(99)00093-0 · Cited by 195 · see citing works
Telomere Shortening in Kidneys with Age
MELK, A., RAMASSAR, V., HELMS, L. M. H., MOORE, R., RAYNER, D., SOLEZ, K., & HALLORAN, P. F. (2000) · Journal of the American Society of Nephrology · doi:10.1681/asn.v113444 · Cited by 189 · see citing works
Telomere reduction in human liver tissues with age and chronic inflammation
Aikata, H., Takaishi, H., Kawakami, Y., Takahashi, S., Kitamoto, M., Nakanishi, T., Nakamura, Y., Shimamoto, F., Kajiyama, G., & Ide, T. (2000) · Experimental Cell Research · doi:10.1006/excr.2000.4862 · Cited by 174 · see citing works
Progressive telomere shortening and telomerase reactivation during hepatocellular carcinogenesis
Miura, N., Horikawa, I., Nishimoto, A., Ohmura, H., Ito, H., Hirohashi, S., Shay, J. W., & Oshimura, M. (1997) · Cancer Genetics and Cytogenetics · doi:10.1016/s0165-4608(96)00329-9 · Cited by 174 · see citing works
Telomere shortening in neurological disorders: an abundance of unanswered questions
Eitan, E., Hutchison, E. R., & Mattson, M. P. (2014) · Trends in Neurosciences · doi:10.1016/j.tins.2014.02.010 · Cited by 158 · see citing works
Du, H.-Y., Pumbo, E., Ivanovich, J., An, P., Maziarz, R. T., Reiss, U. M., Chirnomas, D., Shimamura, A., Vlachos, A., Lipton, J. M., et al. (2009) · Blood · doi:10.1182/blood-2008-07-166421 · Cited by 158 · see citing works
Djojosubroto, M. W., Chin, A. C., Go, N., Schaetzlein, S., Manns, M. P., Gryaznov, S., Harley, C. B., & Rudolph, L. K. (2005) · Hepatology · doi:10.1002/hep.20822 · Cited by 151 · see citing works
Self-citationThe association between telomere length and cancer risk in population studies
Zhu, X., Han, W., Xue, W., Zou, Y., Xie, C., Du, J., & Jin, G. (2016) · Scientific Reports · doi:10.1038/srep22243 · Cited by 146 · see citing works
Genetics of leukocyte telomere length and its role in atherosclerosis
Aviv, A. (2012) · Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis · doi:10.1016/j.mrfmmm.2011.05.001 · Cited by 143 · see citing works
T-cell homeostasis in humans with thymic hypoplasia due to chromosome 22q11.2 deletion syndrome
Piliero, L. M., Sanford, A. N., McDonald-McGinn, D. M., Zackai, E. H., & Sullivan, K. E. (2004) · Blood · doi:10.1182/blood-2003-08-2824 · Cited by 144 · see citing works
Telomeres, sex, reactive oxygen species, and human cardiovascular aging
Aviv, A. (2002) · Journal of Molecular Medicine · doi:10.1007/s00109-002-0377-8 · Cited by 138 · see citing works
Aguado, J., Sola-Carvajal, A., Cancila, V., Revêchon, G., Ong, P. F., Jones-Weinert, C. W., Wallén Arzt, E., Lattanzi, G., Dreesen, O., Tripodo, C., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-13018-3 · Cited by 133 · see citing works
Davy, P., Nagata, M., Bullard, P., Fogelson, N. S., & Allsopp, R. (2009) · Placenta · doi:10.1016/j.placenta.2009.03.005 · Cited by 137 · see citing works
Self-citationHolt, S. E., Norton, J. C., Wright, W. E., & Shay, J. W. (1996) · Methods in Cell Science · doi:10.1007/bf00132889 · Cited by 131 · see citing works
Synchrony in telomere length of the human fetus
Youngren, K., Jeanclos, E., Aviv, H., Kimura, M., Stock, J., Hanna, M., Skurnick, J., Bardeguez, A., & Aviv, A. (1998) · Human Genetics · doi:10.1007/s004390050755 · Cited by 130 · see citing works
Palmer, L. D., Weng, N.-P., Levine, B. L., June, C. H., Lane, H. C., & Hodes, R. J. (1997) · The Journal of Experimental Medicine · doi:10.1084/jem.185.7.1381 · Cited by 129 · see citing works
The illusion of cell immortality
Hayflick, L. (2000) · British Journal of Cancer · doi:10.1054/bjoc.2000.1296 · Cited by 124 · see citing works
Burton, D. G. A., Matsubara, H., & Ikeda, K. (2010) · Experimental Gerontology · doi:10.1016/j.exger.2010.07.005 · Cited by 121 · see citing works
The role of estrogen deficiency in skin ageing and wound healing
Emmerson, E., & Hardman, M. J. (2012) · Biogerontology · doi:10.1007/s10522-011-9322-y · Cited by 118 · see citing works
High glucose-induced replicative senescence: point of no return and effect of telomerase
Blazer, S., Khankin, E., Segev, Y., Ofir, R., Yalon-Hacohen, M., Kra-Oz, Z., Gottfried, Y., Larisch, S., & Skorecki, K. L. (2002) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(02)00818-5 · Cited by 113 · see citing works
Telomere and adaptive immunity
Weng, N.-P. (2008) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2007.11.005 · Cited by 99 · see citing works
Kirwan, M., Vulliamy, T., Marrone, A., Walne, A. J., Beswick, R., Hillmen, P., Kelly, R., Stewart, A., Bowen, D., Schonland, S. O., et al. (2009) · Human Mutation · doi:10.1002/humu.21115 · Cited by 109 · see citing works
Telomere shortening reduces Alzheimer’s disease amyloid pathology in mice
Rolyan, H., Scheffold, A., Heinrich, A., Begus-Nahrmann, Y., Langkopf, B. H., Hölter, S. M., Vogt-Weisenhorn, D. M., Liss, B., Wurst, W., Lie, D. C., et al. (2011) · Brain · doi:10.1093/brain/awr133 · Cited by 106 · see citing works
Recovery of function in osteoarthritic chondrocytes induced by p16INK4a-specific siRNA in vitro
Zhou, H. W. (2004) · Rheumatology · doi:10.1093/rheumatology/keh127 · Cited by 108 · see citing works
Narala, S. R., Allsopp, R. C., Wells, T. B., Zhang, G., Prasad, P., Coussens, M. J., Rossi, D. J., Weissman, I. L., & Vaziri, H. (2008) · Molecular Biology of the Cell · doi:10.1091/mbc.e07-09-0965 · Cited by 106 · see citing works
Self-citation
- Authors
- Allsopp, R. C., Vaziri, H., Patterson, C., Goldstein, S., Younglai, E. V., Futcher, A. B., Greider, C. W., & Harley, C. B.
- Affiliations
- McMaster University (CA)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1992-11
- Volume
- 89
- Issue
- 21
- Pages
- 10114-10118
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC50288
- OpenAlex
- W1998663807
- Cited by
- 2,200
- References
- 44
- Citations by year
- 2026: 14 · 2025: 25 · 2024: 25 · 2023: 39 · 2022: 36 · 2021: 39 · 2020: 42 · 2019: 67 · 2018: 67 · 2017: 52 · 2016: 60 · 2015: 79 · 2014: 82 · 2013: 68 · 2012: 74
- FWCI
- 15.78
- 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)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
- Funders
- U.S. Department of Veterans Affairs
- McMaster University
- Medical Research Council Canada
- National Institutes of Health (5r01ag008708-05)
- Medical Research Council
- National Institute on Aging (AG09383, AG08708)
- 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
- telomere length, replicative capacity, human fibroblasts, telomere shortening, telomerase, chronological age
- MeSH terms
- Base Sequence, Cell Division, Cells, Cultured, DNA, Fibroblasts, Humans, Male, Progeria, Reference Values, Repetitive Sequences, Nucleic Acid, Skin, Skin Physiological Phenomena, Spermatozoa, Skin Aging, Telomere
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