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Disease states associated with telomerase deficiency appear earlier in mice with short telomeres
Open accessAbstract
Mice deficient for the mouse telomerase RNA (mTR-/-) and lacking telomerase activity can only be bred for approximately six generations due to decreased male and female fertility and to an increased embryonic lethality associated with a neural tube closure defect. Although late generation mTR-/- mice show defects in the hematopoietic system, they are viable to adulthood, only showing a decrease in viability in old age. To assess the contribution of genetic background to the effect of telomerase deficiency on viability, we generated mTR-/- mutants on a C57BL6 background, which showed shorter telomeres than the original mixed genetic background C57BL6/129Sv. Interestingly, these mice could be bred for only four generations and the survival of late generation mTR-/- mice decreased dramatically with age as compared with their wild-type counterparts. Fifty percent of the generation 4 mice die at only 5 months of age. This decreased viability with age in the late generation mice is coincident with telomere shortening, sterility, splenic atrophy, reduced proliferative capacity of B and T cells, abnormal hematology and atrophy of the small intestine. These results indicate that telomere shortening in mTR-/- mice leads to progressive loss of organismal viability.
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“However, the cyclin-dependent kinase inhibitor p21 has been shown to participate in the p53-dependent telomere checkpoint response in both human fibroblasts and in TERCÀ/À mice (66,76).”
From Telomeres and telomerase in cancer (2010) · cites this paper as [76]
In the citing paper
“Although it was initially clear that high-turnover tissues are particularly sensitive to telomere length85,101,112”
From The telomere syndromes (2012) · cites this paper as [112]
In the citing paper
“In particular, mice carrying a homozygous germline deletion of the telomerase RNA component gene (Terc−/−) exhibit critically short telomeres and a premature development of age-related pathologies from the second or third generation [8, 18–20, 51, 70, 72, 101, 103]”
From Senescence-related impairment of autophagy induces toxic intraneuronal amyloid-β accumulation in a mouse model of amyloid pathology (2023) · cites this paper as [51]
In the citing paper
“the generation and characterization of the telomerase knockout mouse model has been instrumental in demonstrating that short telomeres result in multiple organismal defects caused by defective tissue regeneration 57, 58, 59”
From The common biology of cancer and ageing (2007) · cites this paper as [59]
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“Telomere FISH and quantification were performed as described previously (Herrera et al., 1999; Poon et al., 1999), except for fluorescein isothiocyanate (FITC)-labeled (CCCTAA) peptide nucleic acid (PNA) probe (Panagene) used in this study.”
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Espejel, S., Franco, S., Sgura, A., Gae, D., Bailey, S. M., Taccioli, G. E., & Blasco, M. A. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf593 · Cited by 130
Self-citationRAP1 Protects from Obesity through Its Extratelomeric Role Regulating Gene Expression
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BackgroundSelf-citationShorter telomeres, accelerated ageing and increased lymphoma in DNA‐PKcs‐deficient mice
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“Metaphase cells were prepared using colcemide treatment and dropped onto slides wetted with 45% acetic acid before hybridization with the telomeric PNA-Cy3 probe (PE Biosystems), and analysed by Q-FISH as described previously (Herrera et al, 1999).”
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“This mTert null allele was backcrossed onto the C57Bl6 background to generate genetically homogeneous mTert mutant mice and to generate average shorter telomeres, which is typical of the C57Bl6 strain ( 30 ).”
MethodBär, C., Povedano, J. M., Serrano, R., Benitez-Buelga, C., Popkes, M., Formentini, I., Bobadilla, M., Bosch, F., & Blasco, M. A. (2016) · Blood · doi:10.1182/blood-2015-08-667485 · Cited by 116
“This result is likely due to the fact that in contrast to the Trf1-deletion model, which shows a very severe and rapid induction of aplastic anemia,(19,20) Tert deficiency leads to a variable penetrance of aplastic anemia with increasing mouse generations.(40,41) Similarly to the Trf1-deficient mouse model, Tert gene…”
ResultSelf-citationVariation at theTERTlocus and predisposition for cancer
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Premature aging in telomerase-deficient zebrafish
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“Only when the telomeres become critically short in later generations (G5 and G6) do telomerasedeficient mice show prominent premature aging symptoms, including impaired spermatogenesis and loss of fertility, bone marrow failure, atrophy of the small intestine, and immunosenescence-related disease (Herrera et al., 1999…”
InfluentialAging, telomeres, and atherosclerosis
EDO, M., & ANDRES, V (2005) · Cardiovascular Research · doi:10.1016/j.cardiores.2004.09.007 · Cited by 112
“The Terc-deficient mouse model has been a valuable tool to investigate the impact of telomere ablation at the organismal level [41–48].”
MethodVera, E., Bernardes de Jesus, B., Foronda, M., Flores, J. M., & Blasco, M. A. (2013) · PLoS ONE · doi:10.1371/journal.pone.0053760 · Cited by 111
“Both telomerase-deficient mice and human diseases involving mutations in telomerase components result in accelerated-aging phenotypes probably due to the depletion of the pools of stem cells followed by organ failure [16,22,23].”
BackgroundSelf-citationTelomeres, Telomerase and Ageing
Saretzki, G. C. (2018) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-981-13-2835-0_9 · Cited by 120
Shorter telomere lengths in patients with severe COVID-19 disease
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“Importantly, by using mouse models that lack telomerase activity, we and others have shown that short telomeres impair the regenerative capacity of tissues leading to loss of tissue homeostasis and degenerative diseases [40].”
BackgroundSelf-citationTelomerase activity in the subventricular zone of adult mice
Caporaso, G. (2003) · Molecular and Cellular Neuroscience · doi:10.1016/s1044-7431(03)00103-9 · Cited by 113
Antagonistic effects of telomerase on cancer and aging in K5-mTert transgenic mice
González-Suárez, E., Geserick, C., Flores, J. M., & Blasco, M. A. (2005) · Oncogene · doi:10.1038/sj.onc.1208413 · Cited by 109
“In particular, telomerase-deficient mice with short telomeres show defects in all highly proliferative tissues (Herrera et al., 1999a, b; Rudolph et al., 1999), as well as in vital organs such as the heart and the kidney (RuizTorres et al., 2002; Leri et al., 2003), resulting in decreased survival…”
BackgroundSelf-citationTelomere Length, Aging, and Somatic Cell Turnover
Hodes, R. J. (1999) · The Journal of Experimental Medicine · doi:10.1084/jem.190.2.153 · Cited by 108
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BackgroundMethodResultInfluentialMammalian telomeres and telomerase: why they matter for cancer and aging
Blasco, M. A. (2003) · European Journal of Cell Biology · doi:10.1078/0171-9335-00335 · Cited by 106
Self-citationThe effect of TERC haploinsufficiency on the inheritance of telomere length
Goldman, F., Bouarich, R., Kulkarni, S., FREEMAN, S., Du, H., Harrington, L. A., Mason, P. J., Londoño‐Vallejo, A., & Bessler, M. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0505318102 · Cited by 105
Increased p53 activity does not accelerate telomere‐driven ageing
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“Observation of telomerase-null cohorts for more than two and half years confirmed, as described in previous work (Herrera et al, 1999; Espejel et al, 2002a,b), that progressive telomere shortening along successive generations (G1–G3) was paralleled by a corresponding progressive decrease in…”
BackgroundMethodSelf-citationLiu, L., Blasco, M. A., & Keefe, D. L. (2002) · EMBO Reports · doi:10.1093/embo-reports/kvf055 · Cited by 102
“The G1 TR–/– mice showed no obvious changes in telomere length and appeared to be normal in development, growth and fertility (Blasco et al., 1997; Lee et al., 1998; Herrera et al., 1999a,b; Rudolph et al., 1999).”
InfluentialSelf-citationTelomere dysfunction in genome instability syndromes
Callén, E., & Surrallés, J. (2004) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2004.06.003 · Cited by 106
“It is common knowledge that telomeres are involved in proliferation capacity [229], and telomere integrity is essential for the normal functionality of haematological system as late-generation telomerase knock-out mice show a diminished haematopoietic production [220,230].”
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“Telomere integrity is also crucial for organismal viability, and in particular for the normal functionality of the hematopoietic system (10,11).”
Telomeres and telomerasePreprint
Blasco, M. A., Gasser, S. M., & Lingner, J. (1999) · Genes & Development · doi:10.1101/gad.13.18.2353 · Cited by 99
“Marı́a Blasco (National Centre of Biotechnology, Spain) further reported that the telomerase deficiency has an even stronger impact on life span if the mTER-null mutation is in a genetic background with shorter telomeres (Herrera et al. 1999).”
Self-citationSpreading of mammalian DNA‐damage response factors studied by ChIP‐chip at damaged telomeres
Meier, A., Fiegler, H., Muñoz, P., Ellis, P., Rigler, D., Langford, C., Blasco, M. A., Carter, N., & Jackson, S. P. (2007) · The EMBO Journal · doi:10.1038/sj.emboj.7601719 · Cited by 100
“Telomere length measurements by Q-FISH and spectral karyotyping Metaphases from pre-senescent BJ and MRC5 cells were prepared for Q-FISH, hybridised with a telomeric probe and analysed as described previously (Herrera et al, 1999; Samper et al, 2000; McIlrath et al, 2001).”
MethodSelf-citationTelomeres and telomerase in cancer stem cells
Ju, Z., & Rudolph, K. L. (2006) · European Journal of Cancer · doi:10.1016/j.ejca.2006.01.040 · Cited by 96
Many ways to telomere dysfunction: in vivo studies using mouse models
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“…partial embryonic mortality due to a defective closure of the neural tube (Herrera et al., 1999a); (ii) small size and severe intestinal atrophy (Herrera et al., 1999b; Rudolph et al., 1999); (iii) spleen atrophy and reduced proliferation of B and T lymphocytes upon mitogenic stimulation…”
BackgroundInfluentialSelf-citationWang, F., Yin, Y., Ye, X., Liu, K., Zhu, H., Wang, L., Chiourea, M., Okuka, M., Ji, G., Dan, J., et al. (2011) · Cell Research · doi:10.1038/cr.2011.201 · Cited by 95
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“…of the loci; ND, not described in detail or ineffective effect by locus alone. been identified to show shorter life spans if continuous cellular proliferation is inhibited by DNA damage (11), DNA repair defects (10, 64, 70), enhanced apoptosis (62), or decreased telomere length (17, 66) (Table 3).”
Gizard, F., Heywood, E. B., Findeisen, H. M., Zhao, Y., Jones, K. L., Cudejko, C., Post, G. R., Staels, B., & Bruemmer, D. (2010) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.110.219808 · Cited by 98
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Telomere maintenance in human B lymphocytes
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“E-mail: martens@ukl.uni-freiburg.de British Journal of Haematology, 2002, 119, 810–818 810 2002 Blackwell Publishing Ltd instability with successive generations coincides with a decreased reactivity of the immune system (Lee et al, 1998; Herrera et al, 1999, 2000).”
BackgroundShort telomeres protect from diet‐induced atherosclerosis in apolipoprotein E‐null mice
Poch, E., Carbonell, P., Franco, S., Díez‐Juan, A., Blasco, M. A., & Andrés, V. (2003) · The FASEB Journal · doi:10.1096/fj.03-0710fje · Cited by 94
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“Progressive loss of organismal viability, including atrophy of the small intestine, was described by Herrera et al. (1999).”
BackgroundPreferential maintenance of critically short telomeres in mammalian cells heterozygous for mTert
Liu, Y., Kha, H. T., Ungrin, M., Robinson, M. O., & Harrington, L. A. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.062549199 · Cited by 94
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Muñoz, P., Blanco, R., de Cárcer, G., Schoeftner, S., Benetti, R., Flores, J. M., Malumbres, M., & Blasco, M. A. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.01339-08 · Cited by 92
“To address whether telomere shortening in K5TRF1 mice triggered chromosomal instability in these mice, we studied chromosomal aberrations involving telomeres by using conventional telomere Q-FISH on metaphase spreads (see Materials and Methods).”
BackgroundInfluentialSelf-citationLocalization-Dependent and -Independent Roles of SLX4 in Regulating Telomeres
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“Q-FISH onmetaphases fromprimaryMEFwas performed as described previously (Herrera et al., 1999).”
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“Terc mice, without detectable telomerase activity, exhibit short telomeres and age-related phenotypes—splenic and intestinal atrophy, reduced body weight, haematological abnormalities, reduced proliferative potential, hair loss and tumour formation [105–107].”
BackgroundUsing naturally occurring tumours in dogs and cats to study telomerase and cancer stem cell biology
Pang, L. Y., & Argyle, D. J. (2009) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2009.02.010 · Cited by 92
“Studies in Terc-/- mice have shown that telomere shortening reduces stem cell function and is associated with impaired organ homeostasis of high turn-over organs, reduced lifespan, impaired organ regeneration and impaired stress responses during ageing [98-101].”
BackgroundSebastián, C., Herrero, C., Serra, M., Lloberas, J., Blasco, M. A., & Celada, A. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0901131 · Cited by 94
“Telomere length differences were not significant between controls and G1 Terc / macrophages, but a significant difference was found when we compared the controls and the G3 Terc / mice, as reported in other cell types (23).”
BackgroundResultSelf-citationLiu, Y., Snow, B. E., Hande, M. P., Baerlocher, G. M., Kickhoefer, V. A., Yeung, D., Wakeham, A. C., Itié, A., Siderovski, D. P., Lansdorp, P. M., et al. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.21.8178-8184.2000 · Cited by 90
“Mice and ES cells disrupted in the telomerase RNA component lack telomerase activity and undergo telomere attrition in vivo (2, 16, 29, 39).”
BackgroundChromatin regulation and non-coding RNAs at mammalian telomeres
Schoeftner, S., & Blasco, M. A. (2009) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2009.09.015 · Cited by 96
Self-citation‘Accelerated aging’: a primrose path to insight?
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Self-citationEspejel, S., Klatt, P., Murcia, J. M., Martín‐Caballero, J., Flores, J. M., Taccioli, G. E., de MURCIA, G., & Blasco, M. A. (2004) · The Journal of Cell Biology · doi:10.1083/jcb.200407178 · Cited by 90
“This may be particularly relevant in the case of telomerase deficiency because the survival of telomerase knockout mice is known to be extremely dependent on the genetic background, due in part to initial differences in telomere length (Herrera et al., 1999).”
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Self-citationRole of Mammalian Rad54 in Telomere Length Maintenance
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“The calibration-corrected telomere fluorescence intensity was calculated as described previously ( 18 ).”
MethodInfluentialSelf-citationPostnatal telomere dysfunction induces cardiomyocyte cell-cycle arrest through p21 activation
Aix, E., Gutiérrez‐Gutiérrez, Ó., Sánchez-Ferrer, C., Aguado, T., & Flores, I. (2016) · The Journal of Cell Biology · doi:10.1083/jcb.201510091 · Cited by 87
“Slides were then fixed in 4% formaldehyde for 20 min and hybridized with a Cy3-labeled peptide nucleic acid probe targeting the telomere repeat sequence (Zijlmans et al., 1997; Herrera et al., 1999; González-Suárez et al., 2000; Flores et al., 2008).”
Flores, I., & Blasco, M. A. (2009) · PLoS ONE · doi:10.1371/journal.pone.0004934 · Cited by 83
“, all mice were dead with in the first 40 weeks of life; not shown) prevented the analysis of the role of p53 in additional skin defects associated to critically short telomeres, such as hair graying and alopecia [27,28].”
BackgroundSelf-citationA metabolic signature predicts biological age in mice
Tomás‐Loba, A., de Jesus, B. B., Mato, J. M., & Blasco, M. A. (2012) · Aging Cell · doi:10.1111/acel.12025 · Cited by 83
“Furthermore, we reasoned that analysis of this age-related metabolomic signature in short-lived, telomerase-deficient (Terc / ), and long-lived TERT transgenics mice could serve to assess the contribution of telomere shortening and telomerase status to the metabolomic changes associated with natural mouse aging (Blasc…”
Self-citationKang, Y., Zhang, H., Zhao, Y., Wang, Y., Wang, W. T., He, Y., Zhang, W. K., Zhang, W., Zhu, X., Zhou, Y., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.02.071 · Cited by 83
Lidzbarsky, G. A., Gutman, D., Shekhidem, H. A., Sharvit, L. E., & Atzmon, G. (2018) · Frontiers in Medicine · doi:10.3389/fmed.2018.00104 · Cited by 85
Tet Enzymes Regulate Telomere Maintenance and Chromosomal Stability of Mouse ESCs
Yang, J., Guo, R., Wang, H., Ye, X., Zhou, Z., Dan, J., Wang, H., Gong, P., Deng, W. W., Yin, Y., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.04.058 · Cited by 83
“Mouse telomeres are quite long, and telomerase Terc- deficient mice following several generations of breeding acquire striking phenotypes associated with telomere dysfunction, including developmental defects, aging, and cancer (Blasco et al., 1997; Herrera et al., 1999; Rudolph et al., 1999).”
MethodInfluentialAnde, S., Greenberg, R. A., Schaetzlein, S., Buer, J., Masutomi, K., Hahn, W. C., Zimmermann, S., Martens, U. M., Manns, M. P., & Rudolph, K. L. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.12.5459-5474.2004 · Cited by 81
“Late-generation telomerase-deficient mice (mTERC (cid:8) / (cid:8) ) have been used as a model system to study the impact of telomere shortening in vivo (6, 24, 28, 42, 43).”
Maser, R. S., Wong, K., Sahin, E., Xia, H., Naylor, M. L., Hedberg, H. M., Artandi, S. E., & DePinho, R. A. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.01354-06 · Cited by 84
“To assess the impact of DNA-PKcs deficiency on classical tissue phenotypes associated with telomere dysfunction in our cohort, we carefully audited anaphase bridging, apoptosis, and tissue integrity in the gastrointestinal and male germ cell compartments—organ systems that are known to display prominent progressive de…”
BackgroundResultEpithelial stem cell exhaustion in the pathogenesis of idiopathic pulmonary fibrosis.
Chilosi, M., Doglioni, C., Murer, B., & Poletti, V. E. (2010) · Sarcoidosis vasculitis and diffuse lung diseases · Cited by 78
Increased life span of human osteoarthritic chondrocytes by exogenous expression of telomerase
Piera-Velázquez, S., Jiménez, S. A., & Stokes, D. G. (2002) · Arthritis & Rheumatism · doi:10.1002/art.10116 · Cited by 79
Hillmer, A. M., Flaquer, A., Hanneken, S., et al. (2008) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2007.11.014 · Cited by 78
Antiaging effects of bioactive molecules isolated from plants and fungi
Martel, J., Ojcius, D. M., Ko, Y., Chang, C., & Young, J. D. (2019) · Medicinal Research Reviews · doi:10.1002/med.21559 · Cited by 79
“Mice that lack telomerase have short telomeres and show premature tissue degeneration associated with reduced stem cells in the bone marrow and skin.(207,208) Telomere length is predictive of mortality from age‐associated pathologies in humans, including heart disease and infections.”
BackgroundA new pleiotropic effect of statins in elderly: modulation of telomerase activity
Boccardi, V., Barbieri, M., Rizzo, M. R., Marfella, R., Esposito, A., Marano, L., & Paolisso, G. (2013) · The FASEB Journal · doi:10.1096/fj.13-232066 · Cited by 75
Cell-Free Fetal DNA, Telomeres, and the Spontaneous Onset of Parturition
Phillippe, M. (2015) · Reproductive Sciences · doi:10.1177/1933719115592714 · Cited by 79
“In an effort to mitigate the effects of telomere sequence loss during cycles of DNA replication, specific cells in some tissues and organisms have been found to express the enzyme telomerase.(90,92,93) Telomerase is a ribonucleoprotein complex that contains a RNA template which allows the de novo addition of TTAGGG re…”
BackgroundTelomere regulation and function during meiosis
Siderakis, M., & Tarsounas, M. (2007) · Chromosome Research · doi:10.1007/s10577-007-1149-7 · Cited by 81
“showed normal fertility in spite of shorter than wildtype telomeres, in the late generations the telomereexhausted chromosomes and associated end-to-end fusions resulted in genomic instability and sterility (Lee et al. 1998, Herrera et al. 1999 ).”
BackgroundInfluentialLaye, M. J., Solomon, T. P. J., Karstoft, K., Pedersen, K. K., Nielsen, S. D., & Pedersen, B. K. (2011) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00997.2011 · Cited by 75
“Telomerase knockout mice have shortened lifespan and increased susceptibility to many age-related diseases (12, 17), which is prevented and also reversed following reactiviation of telomerase (19).”
BackgroundDyskeratosis congenita, telomeres and human ageing
Marciniak, R. A., Johnson, F. B., & Guarente, L. (2000) · Trends in Genetics · doi:10.1016/s0168-9525(00)01984-3 · Cited by 74
The mTOR pathway is necessary for survival of mice with short telomeres
Ferrara‐Romeo, I., Martínez, P., Saraswati, S., Whittemore, K., Graña‐Castro, O., Poluha, L. T., Serrano, R., Hernández-Encinas, E., Blanco‐Aparicio, C., Flores, J. M., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-14962-1 · Cited by 76
Self-citationHuman Genome and Diseases:�Dyskeratosis congenita
Marrone, A., & Mason, P. J. (2003) · Cellular and Molecular Life Sciences · doi:10.1007/s000180300042 · Cited by 76
Telomere regulation in pluripotent stem cells
Huang, Y. Y., Liang, P., Liu, D., Huang, J., & Songyang, Z. (2014) · Protein & Cell · doi:10.1007/s13238-014-0028-1 · Cited by 70
“Many pieces of evidence, including studies of telomerase null mouse models and diseases with premature aging phenotypes such as dyskeratosis congenita (DC), support the notion that telomere shortening is rate limiting for mammalian lifespan and age-related diseases (Blasco et al., 1997; Herrera et al., 1999; Mason et…”
BackgroundMcNees, C. J., Tejera, Á. M., Martínez, P., Murga, M., Mulero, F., Fernández-Capetillo, Ó., & Blasco, M. A. (2010) · The Journal of Cell Biology · doi:10.1083/jcb.200908136 · Cited by 71
“Curiously, we noticed that the mean length of chromosome 11q JCB • VOLUME 188 • NUMBER 5 • 2010 644 extent, q:q dicentrics and p:q fusions (Blasco et al., 1997; Herrera et al., 1999).”
BackgroundMethodInfluentialSelf-citationInfluences of inbreeding and genetics on telomere length in mice
Manning, E., Crossland, J. P., Dewey, M. J., & Zant, G. E. V. (2002) · Mammalian Genome · doi:10.1007/s003350020027 · Cited by 76
“…extends and thus stabilizes telomeres in the face of replicative stress, show few physiological consequences for several generations, but eventually fail to reproduce owing to decreased fertility, as well as increased embryonic lethality due to a neural tube closure defect (Herrera et al. 1999a).”
Backgroundp53: at the crossroad between cancer and ageing
Papazoglu, C., & Mills, A. (2007) · The Journal of Pathology · doi:10.1002/path.2086 · Cited by 75
Telomeres, telomerase, and cancer: life on the edge of genomic stability
Oulton, R., & Harrington, L. A. (2000) · Current Opinion in Oncology · doi:10.1097/00001622-200001000-00013 · Cited by 71
Huang, J., Okuka, M., McLean, M. P., Keefe, D. L., & Liu, L. (2010) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2010.03.026 · Cited by 71
In vivo regulation of telomerase activity and telomere length
Hathcock, K. S., Chiang, Y. J., & Hodes, R. J. (2005) · Immunological Reviews · doi:10.1111/j.0105-2896.2005.00267.x · Cited by 71
Whittemore, K., Derevyanko, A., Martinez, P., Serrano, R., Pumarola, M., Bosch, F., & Blasco, M. A. (2019) · Aging · doi:10.18632/aging.101982 · Cited by 69
“Terc-deficient mice have shorter telomeres with increasing mouse generations and this results in a progressive decrease of both median and maximum longevity [20,21].”
BackgroundSelf-citationMartínez, P., & Blasco, M. A. (2018) · Circulation Research · doi:10.1161/circresaha.118.312202 · Cited by 74
“Telomerase-deficient mice show a worsening of phenotypes with increasing mouse generations owing to inherited progressively shorter telomeres, with the later generations showing severe phenotypes and premature death at prereproductive ages.(74,75,77) These observations indicated for the first time a genetic anticipati…”
BackgroundSelf-citationTaylor, H. A., & Delany, M. E. (2000) · Development Growth & Differentiation · doi:10.1046/j.1440-169x.2000.00540.x · Cited by 68
“Furthermore, recent studies using telomerase-null mice correlate progressive telomere shortening with a general loss of viability and indicate that telomere stability can play a significant role in control of in vivo lifespan, even in rodents with short lifespan (Herrera et al. 1999).”
BackgroundFibroblast growth factor 2 up regulates telomerase activity in neural precursor cells
Haı̈k, S., Gauthier, L., Granotier-Beckers, C., Peyrin, J., Lages, C. S., Dormont, D., & Boussin, F. D. (2000) · Oncogene · doi:10.1038/sj.onc.1203596 · Cited by 66
“…for the telomerase RNA (mTER null mice) present defects in germ cell growth, uterine and intestinal villus atrophy, impaired lymphocyte mitogenesis, diminished hematopoietic reserves, ulcerative dermatitis and alteration of nervous system development (Blasco et al., 1997; Herrera et al., 1999a,b).”
BackgroundControl of Cellular Aging, Tissue Function, and Cancer by p53 Downstream of TelomeresPreprint
Roake, C. M., & Artandi, S. E. (2017) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a026088 · Cited by 70
“Telomere shortening in G6 TERC p53þ/þ mice precipitated a premature aging phenotype, characterized by kyphosis, hair graying, hair loss, villous atrophy in the intestine, and impaired systemic stress responses (Herrera et al. 1999; Rudolph et al. 1999).”
BackgroundLinking Telomere Regulation to Stem Cell Pluripotency
Liu, L. (2016) · Trends in Genetics · doi:10.1016/j.tig.2016.10.007 · Cited by 66
Intrinsic ageing of gut epithelial stem cells
Kirkwood, T. B. L. (2004) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2004.09.004 · Cited by 65
Zhang, L., Zeng, H., & Cheng, W. (2018) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.05.067 · Cited by 67
Siegl-Cachedenier, I., Flores, I., Klatt, P., & Blasco, M. A. (2007) · The Journal of Cell Biology · doi:10.1083/jcb.200704141 · Cited by 64
“Q-FISH was performed as described in Herrera et al. (1999) and Samper et al. (2000).”
InfluentialSelf-citationSirtuin 1, stem cells, aging, and stem cell aging
Mantel, C., & Broxmeyer, H. E. (2008) · Current Opinion in Hematology · doi:10.1097/moh.0b013e3283043819 · Cited by 65
Raj, D. D. A., Moser, J., van der Pol, S. M. A., van Os, R. P., Holtman, I. R., Brouwer, N., Oeseburg, H., Schaafsma, W., Wesseling, E. M., den Dunnen, W. F. A., et al. (2015) · Aging Cell · doi:10.1111/acel.12370 · Cited by 65
“The telomerase knockout mice carry a homozygous deletion for the telomerase RNA component ( mTerc ) gene, which leads to complete loss of Terc expression and telomerase activity (reported in Herrera et al. , 1999 in a C57/BL6 background).”
BackgroundInfluentialSperka, T., Song, Z., Morita, Y., Nalapareddy, K., Guachalla, L. M., Lechel, A., Begus‐Nahrmann, Y., Burkhalter, M. D., Mach, M., Schlaudraff, F., et al. (2011) · Nature Cell Biology · doi:10.1038/ncb2388 · Cited by 63
“were backcrossed seven generations with C57BL/6 mice and crossed with m T e r c +/− mic”
MethodLiu, Y., Snow, B. E., Kickhoefer, V. A., Erdmann, N., Zhou, W., Wakeham, A. C., Gomez, M., Rome, L. H., & Harrington, L. A. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.12.5314-5323.2004 · Cited by 65
“In mice, the disruption of either component also abolishes telomerase activity, leading to telomere attrition, genetic instability, and eventual infertility (4, 15, 26, 44, 48, 61, 76).”
BackgroundTelomerase treatment prevents lung profibrotic pathologies associated with physiological aging
Piñeiro-Hermida, S., Autilio, C., Martínez, P., Bosch, F., Pérez-Gil, J., & Blasco, M. A. (2020) · Journal of Cell Biology · doi:10.1083/jcb.202002120 · Cited by 60
Self-citationTelomere rejuvenation during nuclear reprogramming
Marión, R. M., & Blasco, M. A. (2010) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2010.01.005 · Cited by 62
Self-citationWang, J., Morita, Y., Han, B., Niemann, S., Löffler, B., & Rudolph, K. L. (2016) · Nature Cell Biology · doi:10.1038/ncb3342 · Cited by 64
Telomere dysfunction in hypertension
Fuster, J. J., Dı́ez, J., & Andrés, V. (2007) · Journal of Hypertension · doi:10.1097/hjh.0b013e3282ef6196 · Cited by 63
Metadata
- Authors
- Herrera, E., Samper, E., Martín‐Caballero, J., Flores, J. M., Lee, H., & Blasco, M. A.
- Affiliations
- Consejo Superior de Investigaciones Científicas (ES)
- Universidad Complutense de Madrid (ES)
- Samsung Biomedical Research Institute (KR)
- Corresponding author
- Blasco, María A.
- Venue
- The EMBO Journal
- Published
- 1999-06-01
- Volume
- 18
- Issue
- 11
- Pages
- 2950-2960
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC1171377
- OpenAlex
- W2153094950
- Semantic Scholar
- 2fedd51810926e4acbca1ade7ab5eecd55623631
- Cited by
- 471
- References
- 45
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 8 · 2023: 15 · 2022: 14 · 2021: 13 · 2020: 11 · 2019: 15 · 2018: 15 · 2017: 15 · 2016: 14 · 2015: 9 · 2014: 18 · 2013: 20 · 2012: 20
- FWCI
- 14.72
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- European Molecular Biology Organization
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Keywords
- telomerase deficiency, telomere shortening, genetic background effects, age-related mortality, fertility, embryonic lethality, neural tube defects, hematopoietic defects, splenic atrophy, hematological abnormalities
- MeSH terms
- Aging, Animals, Atrophy, Body Weight, Cells, Cultured, Crosses, Genetic, Female, Genes, Lethal, Hematopoietic System, Infertility, Intestine, Small, Leukocyte Count, Longevity, Lymphocytes, Male, Mice, Inbred C57BL, Spleen, Testis, Time Factors, Telomere, Mice, Knockout, Telomerase, Mice
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