Five dysfunctional telomeres predict onset of senescence in human cells
Open accessAbstract
Replicative senescence is accompanied by a telomere-specific DNA damage response (DDR). We found that DDR+ telomeres occur spontaneously in early-passage normal human cells and increase in number with increasing cumulative cell divisions. DDR+ telomeres at replicative senescence retain TRF2 and RAP1 proteins, are not associated with end-to-end fusions and mostly result from strand-independent, postreplicative dysfunction. On the basis of the calculated number of DDR+ telomeres in G1-phase cells just before senescence and after bypassing senescence by inactivation of wild-type p53 function, we conclude that the accrual of five telomeres in G1 that are DDR+ but nonfusogenic is associated with p53-dependent senescence.
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In replicative senescent cells, TRF2 and RAP1 are still present in some telomeres positive for DDR proteins, suggesting that DDR activation at telomeres is not always a consequence of loss of shelterin components.
“length-independent telomere dysfunction has also been shown to occur in replicative senescent cells, where TRF2 and RAP1 were still present in some telomeres positive for DDR proteins, suggesting that DDR activation at telomeres is not always a consequence of loss of shelterin components (Kaul et al., 2012).”
From Telomeres and cell senescence—size matters not (2017) · cites this paper as Kaul et al., 2012
Cells approaching senescence may proceed to mitosis despite the presence of residual (4 to 5) γH2AX-marked unstable telomere structures.
“Alternatively, cells approaching senescence may proceed to mitosis despite the presence of residual (4 to 5) γH2AX-marked unstable telomere structures [102].”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [102]
Many studies have shown a dependence of telomere length on age: average telomere lengths are shorter in senescent cells than in cells of younger age groups and are also shorter for male than for female.
“Conversely, many studies have shown a dependence of telomere length on age: average telomere lengths are shorter in senescent cells than in cells of younger age groups and are also shorter for male than for female [12-17].”
From Markers of cellular senescence. Telomere shortening as a marker of cellular senescence (2016) · cites this paper as [17]
The single strand tail length at the 3′ end of telomeres varies between approximately 100 and 280 nucleotides in humans.
“The single strand tail length varies between approximately 100 and 280 nucleotides in humans [12-17].”
From Markers of cellular senescence. Telomere shortening as a marker of cellular senescence (2016) · cites this paper as [17]
γ-H2AX foci have a robust correlation with replicative telomere shortening.
“Indeed, γ-H2AX foci have a robust correlation with replicative telomere shortening.”
From Markers of cellular senescence. Telomere shortening as a marker of cellular senescence (2016) · cites this paper as [17]
Formation of telomere dysfunction-induced foci accompanied by γ-H2AX is reversible and the number of telomere dysfunction-induced foci can be reduced during the early G1 phase of the cell cycle.
“Indeed, it was reported that the formation of telomere dysfunction-induced foci accompanied by γ-H2AX is reversible and the number of telomere dysfunction-induced foci can be reduced during the early G1 phase of the cell cycle [17].”
From Markers of cellular senescence. Telomere shortening as a marker of cellular senescence (2016) · cites this paper as [17]
When multiple telomere dysfunction-induced foci are expressed in a cell (observed on fibroblasts and epithelial cells), cellular p53-dependent replicative arrest has been induced.
“When multiple foci of this type are expressed in a cell (observed on fibroblasts and epithelial cells), cellular p53-dependent replicative arrest has been induced [17].”
From Markers of cellular senescence. Telomere shortening as a marker of cellular senescence (2016) · cites this paper as [17]
In cultured human fibroblasts, about five dysfunctional short telomeres are required to trigger senescence.
“For human fibroblasts, a threshold of five dysfunctional short telomeres seems to be needed to trigger a senescence response in vitro50.”
From The telomere syndromes (2012) · cites this paper as [50]
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BackgroundInfluentialShort Telomeres in Key Tissues Initiate Local and Systemic Aging in Zebrafish
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BackgroundTelomeres: Implications for Cancer Development
Bernal, A., & Tusell, L. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19010294 · Cited by 86 · see citing works
“The resulting daughter cells containing the inherited TIFs will continue cycling until they reach the threshold of 4–5 TIFs that will direct cells to replicative senescence (Figure 2) [97].”
BackgroundInfluentialHuang, Y. Y., Hidalgo‐Bravo, A., Zhang, E., Cotton, V. E., Méndez-Bermúdez, A., Wig, G., Medina-Calzada, Z., Neumann, R., Jeffreys, A. J., WINNEY, B. J., et al. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt840 · Cited by 84 · see citing works
Length-dependent processing of telomeres in the absence of telomerase
Fallet, E., Jolivet, P., Soudet, J., Lisby, M., Gilson, É., & Teixeira, M. T. (2014) · Nucleic Acids Research · doi:10.1093/nar/gkt1328 · Cited by 79 · see citing works
Role of Telomeres and Telomeric Proteins in Human Malignancies and Their Therapeutic Potential
Fernandes, S. G., Dsouza, R., Pandya, G., Kirtonia, A., Tergaonkar, V., Lee, S. Y., Garg, M., & Khattar, E. (2020) · Cancers · doi:10.3390/cancers12071901 · Cited by 79 · see citing works
“Critically short telomeres have been shown to activate DNA damage response (DDR) and it has been shown that the presence of approximately five DDR+ telomeres increased the probability of p53 driven senescence [19].”
BackgroundTelomere Maintenance Mechanisms in Cancer: Clinical Implications
Reddel, R. R. (2014) · Current Pharmaceutical Design · doi:10.2174/1381612820666140630101047 · Cited by 78 · see citing works
“The cells finally arrest in G1 phase of the cell cycle and become senescent when the number of telomeric DDR foci reaches 4 or 5 [26].”
BackgroundInfluentialSelf-citationHuman RAP1 specifically protects telomeres of senescent cells from DNA damage
Lototska, L., Yue, J., Li, J., Giraud-Panis, M.-J. E., Songyang, Z., Royle, N. J., Liti, G., Ye, J., Gilson, É., & Méndez-Bermúdez, A. (2020) · EMBO Reports · doi:10.15252/embr.201949076 · Cited by 74 · see citing works
Teyssier, J.-R., Chauvet-Gelinier, J.-C., Ragot, S., & Bonin, B. (2012) · PLoS ONE · doi:10.1371/journal.pone.0049677 · Cited by 73 · see citing works
Martínez, P., & Blasco, M. A. (2018) · Circulation Research · doi:10.1161/circresaha.118.312202 · Cited by 71 · see citing works
“tive senescence or apoptosis and the consequent downstream deleterious effects within tissues.(101) In addition, these findings”
BackgroundNguyen, P. T., Kanno, K., Phạm, Q. T., Kikuchi, Y. S., Kakimoto, M., Kobayashi, T., Otani, Y., Kishikawa, N., Miyauchi, M., Arihiro, K., et al. (2020) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-020-03374-9 · Cited by 69 · see citing works
Role of arterial telomere dysfunction in hypertension
Morgan, R. G., Ives, S. J., Walker, A. E., Cawthon, R., Andtbacka, R. H. I., Noyes, D. R., Lesniewski, L. A., Richardson, R. S., & Donato, A. J. (2014) · Journal of Hypertension · doi:10.1097/hjh.0000000000000157 · Cited by 67 · see citing works
“Interestingly, some studies have suggested that arterial telomere uncapping is more closely linked to P53/P21-induced senescence than telomere shortening in human cells [18,19], including arterial tissues [20].”
BackgroundThe end protection problem—an unexpected twist in the tail
Ruis, P., & Boulton, S. J. (2021) · Genes & Development · doi:10.1101/gad.344044.120 · Cited by 57 · see citing works
“2018); critically short telomeres produced through aging activate ATMbut very rarely undergoNHEJ (Hewitt et al. 2012; Kaul et al. 2012; Hayashi et al. 2015); cells expressing Top-less or TRFcT mutants (which lack t-loops) robustly activate telomeric ATMbut not NHEJ (Okamoto et al.”
BackgroundInfluentialTelomeres and Cancer: Resolving the Paradox
Nassour, J., Schmidt, T. T., & Karlseder, J. (2021) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-050420-023410 · Cited by 64 · see citing works
“After a certain number of cell divisions, however, telomeres become too short to adopt a looped conformation, resulting in their linearization and the exposure of chromosome termini as substrates to the DDR pathway (d’Adda di Fagagna et al. 2003, Herbig et al. 2004, Kaul et al. 2012).”
BackgroundShim, G., Ricoul, M., Hempel, W. M., Azzam, E. I., & Sabatier, L. (2014) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2014.01.001 · Cited by 64 · see citing works
“Proper signaling of approximately 5 dysfunctional telomeres has been proposed [31] to trigger senescence and arrested proliferation.”
BackgroundInfluentialCesare, A. J., Heaphy, C. M., & O’Sullivan, R. J. (2015) · Current Protocols in Cytometry · doi:10.1002/0471142956.cy1240s73 · Cited by 59 · see citing works
Self-citationMechanisms of telomerase inhibition by oxidized and therapeutic dNTPs
Sanford, S. L., Welfer, G. A., Freudenthal, B., & Opresko, P. L. (2020) · Nature Communications · doi:10.1038/s41467-020-19115-y · Cited by 62 · see citing works
Telomeres and Telomerase in the Control of Stem Cells
Lupatov, A. Y., & Yarygin, K. N. (2022) · Biomedicines · doi:10.3390/biomedicines10102335 · Cited by 61 · see citing works
“Dysfunctional telomeres can be found even in early passages, resulting in irreversible cell cycle arrest in some cells [86].”
BackgroundTelomere Length Measurement by Molecular Combing
Kahl, V. F. S., Allen, J. A. M., Nelson, C. B., Sobinoff, A. P., Lee, M., Kilo, T., Vasireddy, R. S., & Pickett, H. A. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00493 · Cited by 59 · see citing works
The role of telomere trimming in normal telomere length dynamics
Pickett, H. A., & Reddel, R. R. (2012) · Cell Cycle · doi:10.4161/cc.19632 · Cited by 59 · see citing works
“This induces a p53-dependent cell cycle arrest known as senescence,(2) when a threshold level of DNA damage response is reached.(3) Despite inducing a DNA damage response, the telomeres of senescent cells appear to be in a functional state that is intermediate between”
BackgroundSelf-citationTelomeres in Plants and Humans: Not So Different, Not So Similar
Schrumpfová, P. P., Fojtová, M., & Fajkus, J. (2019) · Cells · doi:10.3390/cells8010058 · Cited by 57 · see citing works
“In humans, five short telomeres were reported to predict the onset of cell senescence [15].”
BackgroundKannan, N., Huda, N., Tu, L., Droumeva, R., Aubert, G., Chavez, E. A., Brinkman, R. R., Lansdorp, P. M., Emerman, J. T., Abe, S., et al. (2013) · Stem Cell Reports · doi:10.1016/j.stemcr.2013.04.003 · Cited by 56 · see citing works
Yu, Y., Katiyar, S. P., Sundar, D., Kaul, Z., Miyako, E., Zhang, Z., Kaul, S. C., Reddel, R. R., & Wadhwa, R. (2017) · Cell Death and Disease · doi:10.1038/cddis.2017.33 · Cited by 57 · see citing works
“The TIF assay based on the co-localization detection of DNA damage markers (γH2AX) and a telomeric protein (TRF1 or TRF2) was performed as described earlier.(46) Detection of APBs (by double staining of telomeric proteins, such as TRF2, and a PML nuclear body-associated protein, such as PML) was performed as described.”
MethodSelf-citationNo DDRama at chromosome ends: TRF2 takes centre stage
Feuerhahn, S., Chen, L., Luke, B., & Porro, A. (2015) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2015.03.003 · Cited by 52 · see citing works
McCaffrey, J., Sibert, J. G., Zhang, B., Zhang, Y., Hu, W., Riethman, H. C., & Xiao, M. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv878 · Cited by 53 · see citing works
“It has been suggested that the shortest telomere or a small subset of the shortest telomeres in a cell determines the onset of senescence, apoptosis or genome instability (26,27), the ability to systematically measure individual dysfunctionally short (TTAGGG)n tracts (rather than average telomere tract lengths in a sa…”
Aubert, G. (2014) · Progress in molecular biology and translational science · doi:10.1016/b978-0-12-397898-1.00004-9 · Cited by 54 · see citing works
A genomics approach identifies senescence‐specific gene expression regulation
Lackner, D. H., Hayashi, M. T., Cesare, A. J., & Karlseder, J. (2014) · Aging Cell · doi:10.1111/acel.12234 · Cited by 47 · see citing works
“1C,D), which is in agreement with previous reports (Kaul et al., 2012).”
ResultSelf-citationSaccharomyces cerevisiae as a Model to Study Replicative Senescence Triggered by Telomere Shortening
Teixeira, M. T. (2013) · Frontiers in Oncology · doi:10.3389/fonc.2013.00101 · Cited by 47 · see citing works
“This contrasts to the situation in cultured cells where several short telomeres could be required to trigger senescence (Jeyapalan et al., 2007; Kaul et al., 2011).”
ResultResearch progress on sirtuins family members and cell senescence
Wang, T., Wang, Y., Liu, L., Jiang, Z., Li, X., Tong, R., He, J., & Shi, J. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112207 · Cited by 48 · see citing works
High-throughput single-molecule telomere characterizationPreprint
McCaffrey, J., YOUNG, E. A., Lassahn, K. A., Sibert, J. G., Pastor, S. J., Riethman, H. C., & Xiao, M. (2017) · Genome Research · doi:10.1101/gr.222422.117 · Cited by 46 · see citing works
“…using standard culture conditions, such as those we have used here, have different global expression profiles than those propagated under low oxygen conditions (Lackner et al. 2014), suggesting that oxidative stress may impact the clonal subpopulations contributing to the bulk senescing cultures.”
TRF1 and TRF2 binding to telomeres is modulated by nucleosomal organization
Galati, A., Micheli, E., Alicata, C., Ingegnere, T., Cicconi, A., Pusch, M. C., Giraud-Panis, M.-J. E., Gilson, É., & Cacchione, S. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv507 · Cited by 46 · see citing works
“Deprotection of a single telomere is a stochastic event (29) that activates a peculiar DDR signaling that does not contribute to G2/M checkpoint (30) and whose frequency increases with telomere shortening (31).”
Mechanisms driving the ageing heart
Anderson, R., Richardson, G. D., & Passos, J. F. (2017) · Experimental Gerontology · doi:10.1016/j.exger.2017.10.015 · Cited by 46 · see citing works
“has been proposed that a threshold of 5 telomeric DNA damage foci can predict the onset of senescence in human fibroblast cells (Kaul et al., 2012).”
Killedar, A., Stutz, M. D., Sobinoff, A. P., Tomlinson, C. G., Bryan, T. M., Beesley, J., Chenevix‐Trench, G., Reddel, R. R., & Pickett, H. A. (2015) · PLoS Genetics · doi:10.1371/journal.pgen.1005286 · Cited by 44 · see citing works
“Normal human somatic cells replicate until their telomeres diminish to a critical threshold, at which point they enter permanent cell cycle arrest and are constrained to a senescent state [2].”
BackgroundSelf-citationBiomarkers of ageing of humans and non-human primates
Wu, Z., Qu, J. T., Zhang, W., Bao, Z., Bi, Y., Cai, J.-P., Cai, S.-Q., Cao, C.-M., Cao, F., Cao, Z., et al. (2025) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-025-00883-8 · Cited by 49 · see citing works
“For example, the shortening of telomeres has been widely detected to predict senescence in various types of human cells such as skin fibroblasts, stromal fibroblasts, epithelial cells, vascular endothelial cells and mesenchymal stem cells 68–70 .”
Wadhwa, R., Ryu, J., Ahn, H. M., Saxena, N., Chaudhary, A., Yun, C., & Kaul, S. C. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.627463 · Cited by 43 · see citing works
“One likely candidate is DNA damage, particularly at chromosome ends, that is generated spontaneously with each cell division in the form of attrition of the telomeres (5, 6).”
BackgroundConsequences of telomere shortening during lifespan
Henriques, C. M., & Ferreira, M. G. (2012) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2012.09.007 · Cited by 42 · see citing works
“com crucially short telomeres that determine replicative senescence [2], simply knowing the average telomere length is not enough.”
BackgroundLi, X., Li, X., Xie, C., Cai, S., Li, M., Jin, H., Wu, S., Cui, J., Liu, H., & Zhao, Y. B. (2021) · Protein & Cell · doi:10.1007/s13238-021-00879-y · Cited by 42 · see citing works
Dysfunctional telomeres in primary cells from Fanconi anemia FANCD2 patients
Joksić, I., Vujić, D., Guć‐Šćekić, M., Leskovac, A. R., Petrović, S. Ž., Ojani, M., Trujillo‐Quintero, J. P., Surrallés, J., Živković, M., Stanković, A., et al. (2012) · Genome Integrity · doi:10.1186/2041-9414-3-6 · Cited by 40 · see citing works
“[34] have shown that normal human cells can tolerate small number of TIFs, so called “intermediate-state” telomeres.”
BackgroundNoncoding RNAs Controlling Telomere Homeostasis in Senescence and Aging
Rossi, M. S., & Gorospe, M. (2020) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2020.01.010 · Cited by 41 · see citing works
G Protein-Coupled Receptor Systems as Crucial Regulators of DNA Damage Response Processes
Leysen, H., van Gastel, J., Hendrickx, J. O., Santos‐Otte, P., Martin, B., & Maudsley, S. R. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19102919 · Cited by 37 · see citing works
Telomeres as hotspots for innate immunity and inflammation
Nassour, J., Przetocka, S., & Karlseder, J. (2023) · DNA repair · doi:10.1016/j.dnarep.2023.103591 · Cited by 40 · see citing works
Twenty years of t-loops: A case study for the importance of collaboration in molecular biology
Tomáška, Ľ., Cesare, A. J., Al-Turki, T. M., & Griffith, J. D. (2020) · DNA repair · doi:10.1016/j.dnarep.2020.102901 · Cited by 38 · see citing works
“DDR without inducing end-to-end chromosome fusions [108, 109].”
Self-citationMetabolic Alterations in Cellular Senescence: The Role of Citrate in Ageing and Age-Related Disease
Mycielska, M. E., James, E. N., & Parkinson, E. K. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23073652 · Cited by 38 · see citing works
“In telomerase-deficient cells in vitro telomeres shorten until at least five of them are short enough to trigger cellular senescence [23].”
BackgroundMitotic Dysfunction Associated with Aging Hallmarks.
Macedo, J. C., Vaz, S., & Logarinho, E. (2017) · Advances in Experimental Medicine and Biology · doi:10.1007/978-3-319-57127-0_7 · Cited by 33 · see citing works
Telomerase promotes formation of a telomere protective complex in cancer cells
Perera, O. N., Sobinoff, A. P., Teber, E., Harman, A., Maritz, M. F., Yang, S. F., Pickett, H. A., Cesare, A. J., Arthur, J. W., MacKenzie, K. L., et al. (2019) · Science Advances · doi:10.1126/sciadv.aav4409 · Cited by 36 · see citing works
“The DNA-protective effects of hTERT may not be restricted to telomeres, but since telomeric DNA damage is not as efficiently repaired as damage at other sites in the genome (53, 54), and normal somatic cells only need to acquire five TIFs to initiate p53-dependent senescence (55), cancer cells must overcome the telome…”
BackgroundSelf-citationConsequences of telomere replication failure: the other end-replication problem
Brenner, K. A., & Nandakumar, J. (2022) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2022.03.013 · Cited by 37 · see citing works
Regulation of telomere addition at DNA double-strand breaks
Ribeyre, C., & Shore, D. (2013) · Chromosoma · doi:10.1007/s00412-013-0404-2 · Cited by 35 · see citing works
“This somewhat paradoxical behaviour of short de novo telomeres in yeast (abundant accumulation of DNA damage response factors in the absence of checkpoint activation or end fusion) is reminiscent of observations reported recently in which many different mammalian cell lines, usually those possessing relatively low tel…”
BackgroundResultPersistent telomere cohesion protects aged cells from premature senescence
Azarm, K., Bhardwaj, A., Kim, E., & Smith, S. H. (2020) · Nature Communications · doi:10.1038/s41467-020-17133-4 · Cited by 36 · see citing works
Evaluating biomarkers to model cancer risk post cosmic ray exposure
Sridharan, D. M., Asaithamby, A., Blattnig, S. R., Costes, S. V., Doetsch, P. W., Dynan, W. S., Hahnfeldt, P., Hlatky, L., Kidane, Y., Kronenberg, A., et al. (2016) · Life Sciences in Space Research · doi:10.1016/j.lssr.2016.05.004 · Cited by 46 · see citing works
Breaking new ground: Digging into TERRA function
Maicher, A., Lockhart, A., & Luke, B. (2014) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2014.03.012 · Cited by 34 · see citing works
Rnr1, but not Rnr3, facilitates the sustained telomerase-dependent elongation of telomeres
Maicher, A., Gazy, I., Sharma, S., Marjavaara, L., Grinberg, G., Shemesh, K., Chabes, A., & Kupiec, M. (2017) · PLoS Genetics · doi:10.1371/journal.pgen.1007082 · Cited by 32 · see citing works
Telomeres: beacons of autocrine and paracrine DNA damage during skin aging
Victorelli, S. G., & Passos, J. F. (2020) · Cell Cycle · doi:10.1080/15384101.2020.1728016 · Cited by 32 · see citing works
“Furthermore, length-independent telomeric damage has also been observed in cells undergoing replicative senescence [35] and in melanocytic nevi, which are a model of oncogene-induced senescence [36], demonstrating that telomeres that are not critically short can also contribute to persistent DDR signaling in senescenc…”
BackgroundInfluentialLiu, C. C., Ma, D., Yan, T., Fan, X., Poon, Z., Poon, L.-F., Goh, S.-A., Rozen, S., Hwang, W. Y. K., Tergaonkar, V., et al. (2016) · Stem Cells · doi:10.1002/stem.2431 · Cited by 31 · see citing works
NQO1 Stabilizes p53 in Response to Oncogene-Induced Senescence
Liu, K., Jin, B., Wu, C., Yang, J., Zhan, X., Wang, L., Shen, X., Chen, J., Chen, H., & Mao, Z. (2015) · International Journal of Biological Sciences · doi:10.7150/ijbs.11978 · Cited by 28 · see citing works
“Several lines of evidence have implicated that the Arf/p53/p21, p16/pRB and the DNA-damage response (DDR) pathway regulates cellular senescence [6-12].”
BackgroundMason, J. M. O., & McEachern, M. J. (2018) · Current Genetics · doi:10.1007/s00294-018-0822-z · Cited by 28 · see citing works
Targeting Cancer through the Epigenetic Features of Telomeric Regions
Vaquero-Sedas, M. I., & Vega-Palas, M. A. (2019) · Trends in Cell Biology · doi:10.1016/j.tcb.2018.12.006 · Cited by 28 · see citing works
The many types of heterogeneity in replicative senescence
Xu, Z., & Teixeira, M. T. (2019) · Yeast · doi:10.1002/yea.3433 · Cited by 26 · see citing works
Telomere biology: Rationale for diagnostics and therapeutics in cancer
Rousseau, P., & Autexier, C. (2015) · RNA Biology · doi:10.1080/15476286.2015.1081329 · Cited by 27 · see citing works
“e by one or more checkpoints triggered by the presence of at least 5 uncapped or dysfunctional telomeres, preventing the cell to re-enter in the cell cycle and provoking p53-mediated senescence.(15) Thus, affecting a cell’s perception of its telomere length by manipulating the checkpoint signaling could induce senesce…”
BackgroundKrajewska–Włodarczyk, M., Owczarczyk-Saczonek, A. B., Placek, W. J., Osowski, A., & Wojtkiewicz, J. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19020623 · Cited by 27 · see citing works
“When telomeres are shortened down to half of their original length on five chromosomes, phenotypic cell senescence occurs [16].”
BackgroundSingh, R., Kalra, R. S., Hasan, M. K., Kaul, Z., Cheung, C., Huschtscha, L. I., Reddel, R. R., Kaul, S. C., & Wadhwa, R. (2014) · Experimental Cell Research · doi:10.1016/j.yexcr.2014.01.022 · Cited by 26 · see citing works
“Replicative senescence in human fibroblasts was shown to be proportional to the accumulation of DDRþ telomeres [7,8].”
BackgroundSelf-citationStephens, Z. D., & Kocher, J. (2024) · BMC Bioinformatics · doi:10.1186/s12859-024-05807-5 · Cited by 25 · see citing works
“…of ATL, beyond the limited number of arms that are usually studied in detail, using long reads and Telogator2 may be able to corroborate previous observations that the onset of cellular senescence is associated with the shortening a subset of telomeres beyond a critical length [41].”
BackgroundWu, X., & Tanaka, H. (2015) · Oncotarget · doi:10.18632/oncotarget.5083 · Cited by 25 · see citing works
Npl3 stabilizes R‐loops at telomeres to prevent accelerated replicative senescence
Pérez‐Martínez, L., Öztürk, M., Butter, F., & Luke, B. (2020) · EMBO Reports · doi:10.15252/embr.201949087 · Cited by 24 · see citing works
“In telomerase-negative budding yeast, one critically short telomere is sufficient to trigger replicative senescence [11] while approximately five short telomeres are required in human cells [12].”
Nuclear organization in DNA end processing: Telomeres vs double-strand breaks
Marcomini, I., & Gasser, S. M. (2015) · DNA repair · doi:10.1016/j.dnarep.2015.04.024 · Cited by 23 · see citing works
TERRA and Telomere Maintenance in the Yeast Saccharomyces cerevisiae
Zeinoun, B., Teixeira, M. T., & Barascu, A. (2023) · Genes · doi:10.3390/genes14030618 · Cited by 25 · see citing works
“Consistent with this hypothesis of senescence being driven by the shortest telomeres, five dysfunctional telomeres were detected in human cells in culture at the onset of senescence [13].”
Background
- Authors
- Kaul, Z., Cesare, A. J., Huschtscha, L. I., Neumann, A. A., & Reddel, R. R.
- Affiliations
- The University of Sydney (AU)
- Corresponding author
- Reddel, Roger R
- Venue
- The EMBO Reports
- Published
- 2011-12-09
- Volume
- 13
- Issue
- 1
- Pages
- 52-59
- ISSN
- 1469-221X (ISSN-L)
- 1469-3178
- PMC
- PMC3246253
- OpenAlex
- W2109961065
- Cited by
- 225
- References
- 26
- Citations by year
- 2026: 11 · 2025: 11 · 2024: 17 · 2023: 16 · 2022: 10 · 2021: 13 · 2020: 23 · 2019: 12 · 2018: 18 · 2017: 16 · 2016: 21 · 2015: 20 · 2014: 15 · 2013: 8 · 2012: 13
- FWCI
- 8.07
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- EMBO Reports (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Science Foundation (0602009)
- Cancer Australia
- Cancer Institute NSW
- Cure Cancer Australia Foundation
- Cancer Council NSW
- 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 › DNA Repair Mechanisms
- Keywords
- replicative senescence, telomeres, TRF2, Rap1, telomere fusion, p53, senescence bypass, G1 phase, human cells
- MeSH terms
- Cells, Cultured, DNA Damage, Humans, Telomere, Cellular Senescence, Telomere Homeostasis
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