The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
Increased p53 activity does not accelerate telomere‐driven ageing
Open accessAbstract
There is a great interest in determining the impact of p53 on ageing and, for this, it is important to discriminate among the known causes of ageing. Telomere loss is a well-established source of age-associated damage, which by itself can recapitulate ageing in mouse models. Here, we have used a genetic approach to interrogate whether p53 contributes to the elimination of telomere-damaged cells and its impact on telomere-driven ageing. We have generated compound mice carrying three functional copies of the p53 gene (super-p53) in a telomerase-deficient background and we have measured the presence of chromosomal abnormalities and DNA damage in several tissues. We have found that the in vivo load of telomere-derived chromosomal damage is significantly decreased in super-p53/telomerase-null mice compared with normal-p53/telomerase-null mice. Interestingly, the presence of extra p53 activity neither accelerates nor delays telomere-driven ageing. From these observations, we conclude that p53 has an active role in eliminating telomere-damaged cells, and we exclude the possibility of an age-promoting effect of p53 on telomere-driven ageing.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“recent evidence suggest that mouse telomeres suffer a dramatic shortening at old ages and that telomere length can be rate-limiting for mouse longevity (Flores et al, 2008; Garcia-Cao et al, 2006).”
From Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer (2012) · cites this paper as Garcia-Cao et al, 2006
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Telomerase also acts as a longevity gene in the context of the organism by preventing premature telomere attrition, as illustrated by both telomerase-deficient mice and by human diseases due to mutations in telomerase components, which suffer from premature adult stem cell dysfunction and decreased longevity due to accelerated rates of telomere shortening even at the first generation (Armanios et”
From Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer (2012) · cites this paper as Garcia-Cao et al, 2006
The cited source says what the claim attributes to it.
In the citing paper
“recent evidence suggest that mouse telomeres suffer a dramatic shortening at old ages and that telomere length can be rate-limiting for mouse longevity (Flores et al, 2008; Garcia-Cao et al, 2006).”
From Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer (2012) · cites this paper as Garcia-Cao et al, 2006
In the citing paper
“First generation mice lacking the telomerase RNA component Terc show a decrease in both their median and maximum lifespan, and these effects become more pronounced with each subsequent generation 65 .”
From The common biology of cancer and ageing (2007) · cites this paper as [65]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
A DNA damage checkpoint response in telomere-initiated senescence
Fagagna, F. D. D., Reaper, P. M., Clay-Farrace, L., Fiegler, H., Carr, P., von Zglinicki, T., Saretzki, G., Carter, N. P., & Jackson, S. P. (2003) · Nature · doi:10.1038/nature02118 · Cited by 2,917 · cited 2×
“Previous investigators have shown that dysfunctional telomeres trigger the formation of g-H2AX foci (d’Adda di Fagagna et al, 2003; Takai et al, 2003; Hao et al, 2004) and, moreover, that there is an age-dependent increase in the number of cells containing g-H2AX foci (Sedelnikova et al, 2004).”
Backgroundp53 is required for radiation-induced apoptosis in mouse thymocytes
Lowe, S. W., Schmitt, E. M., Smith, S. W., Osborne, B. A., & Jacks, T. (1993) · Nature · doi:10.1038/362847a0 · Cited by 2,864
Switching and Signaling at the Telomere
Blackburn, E. H. (2001) · Cell · doi:10.1016/s0092-8674(01)00492-5 · Cited by 2,139
Telomere 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
Self-citationAssociation between telomere length in blood and mortality in people aged 60 years or older
Cawthon, R. M., Smith, K. R., O'Brien, E., Sivatchenko, A., & Kerber, R. A. (2003) · The Lancet · doi:10.1016/s0140-6736(03)12384-7 · Cited by 1,761
p53 mutant mice that display early ageing-associated phenotypes
Tyner, S. D., Venkatachalam, S., Choi, J., Jones, S., Ghebranious, N., Igelmann, H., Lu, X., Soron, G., Cooper, B., Brayton, C., et al. (2002) · Nature · doi:10.1038/415045a · Cited by 1,459
DNA Damage Foci at Dysfunctional Telomeres
Takai, H., Smogorzewska, A., & de Lange, T. (2003) · Current Biology · doi:10.1016/s0960-9822(03)00542-6 · Cited by 1,409
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 · cited 2×
“…of telomere dysfunction in somatic cells is a generalized proliferative defect culminating in diverse symptoms of tissue atrophy that become particularly evident in highly proliferative tissues such as the intestine, spleen and testis (Lee et al, 1998; Herrera et al, 1999; Rudolph et al, 1999).”
BackgroundSelf-citationEssential role of mouse telomerase in highly proliferative organs
Lee, H.-W., Blasco, M. A., Gottlieb, G. J., Horner, J. W., Greider, C. W., & DePinho, R. A. (1998) · Nature · doi:10.1038/33345 · Cited by 1,270 · cited 1×
“…of telomere dysfunction in somatic cells is a generalized proliferative defect culminating in diverse symptoms of tissue atrophy that become particularly evident in highly proliferative tissues such as the intestine, spleen and testis (Lee et al, 1998; Herrera et al, 1999; Rudolph et al, 1999).”
BackgroundSelf-citationTelomere dysfunction promotes non-reciprocal translocations and epithelial cancers in mice
Artandi, S. E., Chang, S., Lee, S.-L., Alson, S., Gottlieb, G. J., Chin, L., & DePinho, R. A. (2000) · Nature · doi:10.1038/35020592 · Cited by 1,085
Chin, L., Artandi, S. E., Shen, Q., Tam, A., Lee, S.-L., Gottlieb, G. J., Greider, C. W., & DePinho, R. A. (1999) · Cell · doi:10.1016/s0092-8674(00)80762-x · Cited by 979 · cited 3×
“The tumour suppressor p53 is an important sensor of dysfunctional telomeres (Chin et al, 1999; Gonzalez-Suarez et al, 2000; Smogorzewska & de Lange, 2002; Leri et al, 2003; Sharpless & DePinho, 2004).”
The RNA component of telomerase is mutated in autosomal dominant dyskeratosis congenita
Vulliamy, T., Marrone, A., Goldman, F., Dearlove, A., Bessler, M., Mason, P. J., & Dokal, I. (2001) · Nature · doi:10.1038/35096585 · Cited by 960
Protection of mammalian telomeres
de Lange, T. (2002) · Oncogene · doi:10.1038/sj.onc.1205080 · Cited by 942
Senescing human cells and ageing mice accumulate DNA lesions with unrepairable double-strand breaks
Sedelnikova, O. A., Horikawa, I., Zimonjic, D. B., Popescu, N. C., Bonner, W. M., & Barrett, J. C. (2004) · Nature Cell Biology · doi:10.1038/ncb1095 · Cited by 790
Modulation of mammalian life span by the short isoform of p53
Maier, B., Gluba, W., Bernier, B., Turner, T., Mohammad, K., Guise, T., Sutherland, A., Thorner, M., & Scrable, H. (2004) · Genes & Development · doi:10.1101/gad.1162404 · Cited by 586
Aging and Genome Maintenance: Lessons from the Mouse?
Hasty, P., Campisi, J., Hoeijmakers, J., van Steeg, H., & Vijg, J. (2003) · Science · doi:10.1126/science.1079161 · Cited by 553 · cited 1×
“Ageing is produced by the accumulation of cellular damage that eventually results in tissue dysfunction (Hasty et al, 2003).”
Background'Super p53' mice exhibit enhanced DNA damage response, are tumor resistant and age normally
García‐Cao, I., García‐Cao, M., Martín‐Caballero, J., Criado, L. M., Klatt, P., Flores, J. M., Weill, J., Blasco, M. A., & Serrano, M. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf595 · Cited by 529
Self-citationTelomeres, stem cells, senescence, and cancer
Sharpless, N. E., & DePinho, R. A. (2004) · Journal of Clinical Investigation · doi:10.1172/jci20761 · Cited by 488
Different telomere damage signaling pathways in human and mouse cells
Smogorzewska, A., & de Lange, T. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf433 · Cited by 482
Disease states associated with telomerase deficiency appear earlier in mice with short telomeres
Herrera, E., Samper, E., Martín‐Caballero, J., Flores, J. M., Lee, H., & Blasco, M. A. (1999) · The EMBO Journal · doi:10.1093/emboj/18.11.2950 · Cited by 471 · cited 3×
“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-citationTAT-Mediated Protein Transduction into Mammalian Cells
Becker‐Hapak, M., McAllister, S. S., & Dowdy, S. F. (2001) · Methods · doi:10.1006/meth.2001.1186 · Cited by 390
Telomerase-deficient mice with short telomeres are resistant to skin tumorigenesis
González-Suárez, E., Samper, E., Flores, J. M., & Blasco, M. A. (2000) · Nature Genetics · doi:10.1038/79089 · Cited by 347
Self-citationSamper, E., Goytisolo, F. A., Slijepčević, P., van Buul, P. P. W., & Blasco, M. A. (2000) · EMBO Reports · doi:10.1093/embo-reports/kvd051 · Cited by 317
Self-citationLeri, A., Franco, S., Zacheo, A., Barlucchi, L., Chimenti, S., Limana, F., Nadal‐Ginard, B., Kajstura, J., Anversa, P., & Blasco, M. A. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg013 · Cited by 313
Self-citationMidgley, C., Owens, B. M., Briscoe, C. V., Thomas, D. B., Lane, D. P., & Hall, P. A. (1995) · Journal of Cell Science · doi:10.1242/jcs.108.5.1843 · Cited by 233
Mammalian Ku86 mediates chromosomal fusions and apoptosis caused by critically short telomeres
Espejel, S., Franco, S., Rodríguez, S., Bouffler, S. D., Cigudosa, J. C., & Blasco, M. A. (2002) · The EMBO Journal · doi:10.1093/emboj/21.9.2207 · Cited by 222
Self-citationTumor suppression and normal aging in mice with constitutively high p53 activity
Mendrysa, S. M., O'Leary, K. A., McElwee, M. K., Michalowski, J., Eisenman, R. N., Powell, D. A., & Perry, M. E. (2006) · Genes & Development · doi:10.1101/gad.1378506 · Cited by 210
Increased gene dosage of Ink4a/Arf results in cancer resistance and normal agingPreprint
Matheu, A., Pantoja, C., Efeyan, A., Criado, L. M., Martín‐Caballero, J., Flores, J. M., Klatt, P., & Serrano, M. (2004) · Genes & Development · doi:10.1101/gad.310304 · Cited by 140
Self-citationLong lifespan in worms with long telomeric DNA
Joeng, K. S., Song, E. J., Lee, K., & Lee, J. (2004) · Nature Genetics · doi:10.1038/ng1356 · Cited by 131
Functional interaction between DNA‐PKcs and telomerase in telomere length maintenance
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-citationGodley, L. A., Kopp, J. B., Eckhaus, M., Paglino, J. J., Owens, J., & VARMUS, H. E. (1996) · Genes & Development · doi:10.1101/gad.10.7.836 · Cited by 120
Many ways to telomere dysfunction: in vivo studies using mouse models
Goytisolo, F. A., & Blasco, M. A. (2002) · Oncogene · doi:10.1038/sj.onc.1205085 · Cited by 96
Self-citationAge-dependent silencing of globin transgenes in the mouse
Robertson, G. (1996) · Nucleic Acids Research · doi:10.1093/nar/24.8.1465 · Cited by 93
Phosphorylation of H2AX at Short Telomeres in T Cells and Fibroblasts
Hao, L.-Y., Strong, M. A., & Greider, C. W. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m403924200 · Cited by 71
A Globin Enhancer Acts by Increasing the Proportion of Erythrocytes Expressing a Linked Transgene
Sutherland, H. G. E., Martin, D. I. K., & Whitelaw, E. (1997) · Molecular and Cellular Biology · doi:10.1128/mcb.17.3.1607 · Cited by 70
Replicative senescence and the art of counting
von Zglinicki, T. (2003) · Experimental Gerontology · doi:10.1016/j.exger.2003.09.015 · Cited by 69
Induction of senescence by oncogenic ras
Palmero, I., & Serrano, M. (2001) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(01)33060-4 · Cited by 67
Self-citationAn apoptotic defect in lens differentiation caused by human p53 is rescued by a mutant allele.
Nakamura, T., Pichel, J. G., Williams‐Simons, L., & Westphal, H. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.13.6142 · Cited by 64
Cohn, S. M., Roth, K. A., Birkenmeier, E. H., & Gordon, J. I. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.3.1034 · Cited by 47
Telomeres in cancer and aging: lessons from the mouse
Blasco, M. A. (2003) · Cancer Letters · doi:10.1016/s0304-3835(02)00705-x · Cited by 36
Self-citationInsulators to improve expression of a 3′IgH LCR-driven reporter gene in transgenic mouse models
Guglielmi, L., Bert, M. L., Truffinet, V., Cogné, M., & Denizot, Y. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(03)01185-9 · Cited by 33
Cited by
Sorted by citations
Cellular senescence in cancer and aging.
Collado, M., Blasco, M. A., & Serrano, M. (2007) · Cell · doi:10.1016/j.cell.2007.07.003 · Cited by 1,708
“Moreover, increased p53 activity in super-p53 mice decreases the amount of telomeredamaged cells in aged mice (Garcia-Cao et al., 2006).”
Self-citationThe common biology of cancer and ageing
Finkel, T., Serrano, M., & Blasco, M. A. (2007) · Nature · doi:10.1038/nature05985 · Cited by 988
Self-citationTelomere length, stem cells and aging
Blasco, M. A. (2007) · Nature Chemical Biology · doi:10.1038/nchembio.2007.38 · Cited by 747
Self-citationTissue damage and senescence provide critical signals for cellular reprogramming in vivo
Mosteiro, L., Pantoja, C., Alcazar, N., Marión, R. M., Chondronasiou, D., Rovira, M., Fernandez-Marcos, P. J., Muñoz-Martin, M., Blanco-Aparicio, C., Pastor, J., et al. (2016) · Science · doi:10.1126/science.aaf4445 · Cited by 589
“activity that leads to critically short telomere length (33, 34).”
BackgroundSelf-citationBernardes de Jesus, B., Vera, E., Schneeberger, K., Tejera, A. M., Ayuso, E., Bosch, F., & Blasco, M. A. (2012) · EMBO Molecular Medicine · doi:10.1002/emmm.201200245 · Cited by 548
“…stem cell dysfunction and decreased longevity due to accelerated rates of telomere shortening even at the first generation (Armanios et al, 2007; Blasco et al, 1997; Garcia-Cao et al, 2006; Herrera et al, 1999; Mitchell et al, 1999; Tsakiri et al, 2007; Vulliamy et al, 2001; Yamaguchi et al, 2005).”
Self-citation
Metadata
- Authors
- García‐Cao, I., García‐Cao, M., Tomás‐Loba, A., Martin‐Caballero, J., Flores, J. M., Klatt, P., Blasco, M. A., & Serrano, M.
- Affiliations
- Universidad Complutense de Madrid (ES)
- Corresponding author
- Serrano, Manuel
- Venue
- The EMBO Reports
- Published
- 2006-03-31
- Volume
- 7
- Issue
- 5
- Pages
- 546-552
- ISSN
- 1469-221X (ISSN-L)
- 1469-3178
- PMC
- PMC1479549
- OpenAlex
- W1979784082
- Cited by
- 102
- References
- 41
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 3 · 2022: 2 · 2021: 2 · 2020: 1 · 2019: 2 · 2018: 2 · 2017: 5 · 2016: 5 · 2015: 1 · 2014: 1 · 2013: 4 · 2012: 10
- FWCI
- 8.42
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- EMBO Reports (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Hispana (submittedVersion, cc-by)
- 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
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Keywords
- p53, telomere loss, chromosomal damage, DNA damage, p53 overexpression
- MeSH terms
- Aging, Animals, Kinetics, Mice, Inbred C57BL, Mice, Transgenic, Up-Regulation, Tumor Suppressor Protein p53, Telomere, Mice, Knockout, Gene Dosage, Telomerase, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
