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.
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First generation mice lacking the telomerase RNA component Terc show decreased median and maximum lifespan, and these effects become more pronounced with each subsequent generation.
“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]
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Cites
p53 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 · see citing works
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 2,855 · cited 2× · see citing works
“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).”
BackgroundTelomere 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-citationSwitching and Signaling at the Telomere
Blackburn, E. H. (2001) · Cell · doi:10.1016/s0092-8674(01)00492-5 · Cited by 2,097 · see citing works
Association 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 · see citing works
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 · see citing works
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 · 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 · cited 2× · see citing works
“…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× · see citing works
“…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 · see citing works
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× · see citing works
“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 · see citing works
Protection of mammalian telomeres
de Lange, T. (2002) · Oncogene · doi:10.1038/sj.onc.1205080 · Cited by 942 · see citing works
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 · see citing works
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 · see citing works
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× · see citing works
“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 · see citing works
Self-citationDifferent 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 · see citing works
Telomeres, stem cells, senescence, and cancer
Sharpless, N. E., & DePinho, R. A. (2004) · Journal of Clinical Investigation · doi:10.1172/jci20761 · Cited by 479 · see citing works
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× · see citing works
“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 384 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 215 · see citing works
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 · see citing works
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 137 · see citing works
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 · see citing works
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 128 · see citing works
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 119 · see citing works
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 94 · see citing works
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 · see citing works
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 75 · see citing works
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 · see citing works
Replicative senescence and the art of counting
von Zglinicki, T. (2003) · Experimental Gerontology · doi:10.1016/j.exger.2003.09.015 · Cited by 68 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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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 · see citing works
“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 · see citing works
Self-citationTelomere length, stem cells and aging
Blasco, M. A. (2007) · Nature Chemical Biology · doi:10.1038/nchembio.2007.38 · Cited by 747 · see citing works
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 · see citing works
“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 · see citing works
“…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-citationCoping with stress: multiple ways to activate p53
Horn, H. F., & Vousden, K. H. (2007) · Oncogene · doi:10.1038/sj.onc.1210263 · Cited by 522 · see citing works
“Increasing potential p53 activity, by adding an extra copy of p53 or reducing (but not eliminating) expression of Mdm2, resulted in apparently normal mice that were resistant to tumour development (Garcia-Cao et al., 2002, 2006; Mendrysa et al., 2006).”
BackgroundTelomerase Reverse Transcriptase Delays Aging in Cancer-Resistant Mice
Tomás-Loba, A., Flores, I., Fernández-Marcos, P. J., Cayuela, M. L., Maraver, A., Tejera, A., Borrás, C., Matheu, A., Klatt, P., Flores, J. M., et al. (2008) · Cell · doi:10.1016/j.cell.2008.09.034 · Cited by 484 · see citing works
“Longevity is progressively shortened upon successive intercrossing of telomerase-deficient mice (Blasco, 2005), an effect already noticeable at the first generation of Terc null mice where both the median and maximum life span are reduced (Garcia-Cao et al., 2006).”
BackgroundSelf-citationDelayed ageing through damage protection by the Arf/p53 pathway
Matheu, A., Maraver, A., Klatt, P., Flores, I., Garcia-Cao, I., Borras, C., Flores, J. M., Viña, J., Blasco, M. A., & Serrano, M. (2007) · Nature · doi:10.1038/nature05949 · Cited by 466 · see citing works
Self-citationDNA damage checkpoints in stem cells, ageing and cancer
Sperka, T., Wang, J., & Rudolph, K. L. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3420 · Cited by 393 · see citing works
Two faces of p53: aging and tumor suppression
Rodier, F., Campisi, J., & Bhaumik, D. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm744 · Cited by 399 · see citing works
“However, the accelerated aging shown by telomerase-null mice was not further accelerated when these mice were crossed with super-53 mice (90).”
BackgroundThe role of DNA damage and repair in aging through the prism of Koch-like criteria
Moskalev, A. A., Shaposhnikov, M. V., Plyusnina, E. N., Zhavoronkov, A., Budovsky, A., Yanai, H., & Fraifeld, V. E. (2013) · Ageing Research Reviews · doi:10.1016/j.arr.2012.02.001 · Cited by 387 · see citing works
The longest telomeres: a general signature of adult stem cell compartments
Flores, I., Canela, A., Vera, E., Tejera, A., Cotsarelis, G., & Blasco, M. A. (2008) · Genes & Development · doi:10.1101/gad.451008 · Cited by 352 · see citing works
“A role for telomere shortening in mouse aging and stem cell aging was suggested previously by the reduction in both median and maximum life span (García-Cao et al. 2006) as well as in 660 GENES & DEVELOPMENT stem cell functionality (Flores et al. 2005) found in earlygeneration Terc−/− mice, which…”
BackgroundInfluentialSelf-citationCellular senescence and organismal aging
Jeyapalan, J. C., & Sedivy, J. M. (2008) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2008.04.001 · Cited by 347 · see citing works
Sulak, M. A., Fong, L., Mika, K. M., Chigurupati, S., Yon, L., Mongan, N. P., Emes, R. D., & Lynch, V. J. (2016) · eLife · doi:10.7554/elife.11994 · Cited by 342 · see citing works
Cancer and Aging: Two Tightly Interconnected Biological Processes
Berben, L., Floris, G., Wildiers, H. P. M. W., & Hatse, S. (2021) · Cancers · doi:10.3390/cancers13061400 · Cited by 241 · see citing works
“[36] studied the impact of P53 on the elimination of telomeredamaged cells and/or on telomere-driven aging.”
BackgroundInfluentialThe Rate of Increase of Short Telomeres Predicts Longevity in Mammals
Vera, E., de Jesus, B. B., Foronda, M., Flores, J. M., & Blasco, M. A. (2012) · Cell Reports · doi:10.1016/j.celrep.2012.08.023 · Cited by 220 · see citing works
“Evidence from telomerase loss-of-expression and gain-ofexpression transgenic mouse models suggests that telomere length may be rate limiting for mouse longevity (Garcı́a-Cao et al., 2006; Tomás-Lobaet al., 2008).”
BackgroundSelf-citationA ‘higher order’ of telomere regulation: telomere heterochromatin and telomeric RNAs
Schoeftner, S., & Blasco, M. A. (2009) · The EMBO Journal · doi:10.1038/emboj.2009.197 · Cited by 214 · see citing works
“…in stem cell dysfunction, premature loss of tissue regeneration, and reduced life span, as shown in the context of telomerase-deficient mice (Blasco et al, 1997; Herrera et al, 1999; Rudolph et al, 1999; Gonzalez-Suarez et al, 2000; Collins and Mitchell, 2002; Blasco, 2005; Garcia-Cao et al, 2006).”
BackgroundSelf-citationTargeting the p53 signaling pathway in cancer therapy – the promises, challenges and perils
Stegh, A. H. (2012) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2011.643299 · Cited by 192 · see citing works
Telomeres in cancer and ageing
Donate, L. E., & Blasco, M. A. (2010) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2010.0291 · Cited by 189 · see citing works
Self-citationCancer and ageing: convergent and divergent mechanisms
Serrano, M., & Blasco, M. A. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2242 · Cited by 182 · see citing works
Self-citationLe, O. N. L., Rodier, F., Fontaine, F., Coppe, J., Campisi, J., DeGregori, J., Laverdière, C., Kokta, V., Haddad, E., & Beauséjour, C. M. (2010) · Aging Cell · doi:10.1111/j.1474-9726.2010.00567.x · Cited by 168 · see citing works
MicroRNAs in cancer cell death pathways: Apoptosis and necroptosis
Shirjang, S., Mansoori, B., Asghari, S., Duijf, P. H. G., Mohammadi, A., Gjerstorff, M. F., & Baradaran, B. (2019) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2019.05.017 · Cited by 169 · see citing works
The evolution of senescence from a comparative perspective
Ricklefs, R. E. (2008) · Functional Ecology · doi:10.1111/j.1365-2435.2008.01420.x · Cited by 165 · see citing works
The Role of Telomere Biology in Cancer
Xu, L., Li, S., & Stohr, B. A. (2013) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-020712-164030 · Cited by 160 · see citing works
Role of shelterin in cancer and aging
Martínez, P., & Blasco, M. A. (2010) · Aging Cell · doi:10.1111/j.1474-9726.2010.00596.x · Cited by 162 · see citing works
“aplasia, kidney dysfunction, defective bone marrow and proliferative defects of neural stem cells (Lee et al., 1998; Herrera et al., 1999; Samper et al., 2002; Leri et al., 2003; Ferron et al., 2004; Blasco, 2005; Garcia-Cao et al., 2006).”
BackgroundSelf-citationTelomerase, senescence and ageing
Shawi, M., & Autexier, C. (2008) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2007.11.007 · Cited by 156 · see citing works
The Senescence Markers p16INK4A, p14ARF/p19ARF, and p21 in Organ Development and Homeostasis
Wagner, K., & Wagner, N. (2022) · Cells · doi:10.3390/cells11121966 · Cited by 156 · see citing works
Aging by epigenetics—A consequence of chromatin damage?
Sedivy, J. M., Gowrishankar, B., & Adams, P. D. (2008) · Experimental Cell Research · doi:10.1016/j.yexcr.2008.02.023 · Cited by 153 · see citing works
“Moreover, manipulation of the cell signals that initiate senescence, such as telomere length and expression of the proliferation inhibitor p16INK4a [66–68,70,73–80], can modulate some aspects of organismal aging [70–72].”
BackgroundThe role of telomeres and telomerase in stem cell aging
Flores, I., & Blasco, M. A. (2010) · FEBS Letters · doi:10.1016/j.febslet.2010.07.042 · Cited by 145 · see citing works
“without Terc increases [22,31].”
Self-citationTelomere Shortening Reduces Regenerative Capacity after Acute Kidney Injury
Westhoff, J. H., Schildhorn, C., Jacobi, C., Hömme, M., Hartner, A., Braun, H., Kryzer, C., Wang, C., von Zglinicki, T., Kränzlin, B., et al. (2010) · Journal of the American Society of Nephrology · doi:10.1681/asn.2009010072 · Cited by 139 · see citing works
Telomerase abrogation dramatically accelerates TRF2-induced epithelial carcinogenesis
Blanco, R., Muñoz, P., Flores, J. M., Klatt, P., & Blasco, M. A. (2007) · Genes & Development · doi:10.1101/gad.406207 · Cited by 135 · see citing works
“The fact that K5TRF2 mice show increased cancer in spite of having critically short telomeres is in marked contrast to telomerase-deficient mice with short telomeres, which are resistant to skin carcinogenic treatments (González-Suárez et al. 2000).”
BackgroundSelf-citationRegulation of glucose metabolism by p53: Emerging new roles for the tumor suppressor
Madan, E., Gogna, R., Bhatt, M. L. B., Pati, U., Kuppusamy, P., & Mahdi, A. A. (2011) · Oncotarget · doi:10.18632/oncotarget.389 · Cited by 130 · see citing works
“Remarkably, even the first generation of telomerasedeficient mice already has a shortened lifespan, which becomes shorter and shorter in subsequent generations [62].”
BackgroundThe Arf/p53 Pathway in Cancer and Aging
Matheu, A., Maraver, A., & Serrano, M. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-6851 · Cited by 129 · see citing works
“Moreover, the presence ofthe transgenic p53 allele in mice deficient in telomerase does not aggravate the accelerated aging of telomerase-deficient mice ( 20 ).”
BackgroundSelf-citationClassic and novel roles of p53: prospects for anticancer therapy
Fuster, J. J., Sanz-Gonzalez, S. M., Moll, U. M., & Andrés, V. (2007) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2007.03.002 · Cited by 126 · see citing works
“telomere shortening [40].”
Telomeres and telomerase as therapeutic targets to prevent and treat age-related diseases
Bär, C., & Blasco, M. A. (2016) · F1000Research · doi:10.12688/f1000research.7020.1 · Cited by 115 · see citing works
Self-citationmiR-33-mediated downregulation of p53 controls hematopoietic stem cell self-renewal
Herrera-Merchan, A., Cerrato, C., Luengo, G., Domı́nguez, O., Piris, M. A., Serrano, M., & González, S. (2010) · Cell Cycle · doi:10.4161/cc.9.16.12598 · Cited by 110 · see citing works
“This reduction in the HSC numbers in sp53 mice could be caused by an apoptotic effect, and assays of cell carcinogen-induced tumors.(13) It remains unclear if the elevated p53 activity in these mice alters HSC frequency or self-renewal capacity.”
BackgroundSelf-citationTelomeres in aging and disease: lessons from zebrafish
Carneiro, M. C., de Castro, I. P., & Ferreira, M. G. (2016) · Disease Models & Mechanisms · doi:10.1242/dmm.025130 · Cited by 105 · see citing works
Anti‐aging activity of the Ink4/Arf locus
Matheu, A., Maraver, A., Collado, M., Garcı́a-Cao, I., Cañamero, M., Borrás, C., Flores, J. M., Klatt, P., Viña, J., & Serrano, M. (2009) · Aging Cell · doi:10.1111/j.1474-9726.2009.00458.x · Cited by 106 · see citing works
“Interestingly, a single p53-tg allele had no impact on normal aging or on aging driven by short telomeres (Garcia-Cao et al., 2002; Garcia-Cao et al., 2006), but in combination with the Ink4/Arf transgenic allele (Ink4/Arf/p53-tg mice) it resulted in an increased median longevity (Matheu et al.”
BackgroundMethodSelf-citationRuzankina, Y., Schoppy, D. W., Asare, A., Clark, C. E., Vonderheide, R. H., & Brown, E. J. (2009) · Nature Genetics · doi:10.1038/ng.441 · Cited by 104 · see citing works
“and by limiting the accumulation of damaged cells that impede repopulation from competent progenitor”
Begus‐Nahrmann, Y., Lechel, A., Obenauf, A. C., Nalapareddy, K., Peit, E., Hoffmann, E. M., Schlaudraff, F., Liss, B., Schirmacher, P., Kestler, H. A., et al. (2009) · Nature Genetics · doi:10.1038/ng.426 · Cited by 104 · see citing works
“Of note, overexpression of an extra copy of naturally regulated, wild-type p53 did not affect the lifespan of telomere-dysfunctional mic”
BackgroundThe p53 tumor suppressor protein regulates hematopoietic stem cell fate
Asai, T., Liu, Y., Bae, N., & Nimer, S. D. (2010) · Journal of Cellular Physiology · doi:10.1002/jcp.22561 · Cited by 92 · see citing works
“These studies illustrate the tenuous relationship between tumor suppression and HSC aging (Gatza et al., 2007).”
BackgroundTRF1 Controls Telomere Length and Mitotic Fidelity in Epithelial Homeostasis
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 89 · see citing works
“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-citationChromatin 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 87 · see citing works
Self-citationAging-Associated Changes in Hematopoiesis and Leukemogenesis: What's the Connection?
Henry, C. J., Marusyk, A., & DeGregori, J. V. (2011) · Aging · doi:10.18632/aging.100351 · Cited by 83 · see citing works
“Chronic activation of p53 results in a suppression of DNA replication, decreased cellular proliferation, and ultimately cellular senescence or death [89, 94, 95] (however, note that increased p53dependent tumor suppression can be obtained without accelerated aging [96, 97]).”
BackgroundA 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 · see citing works
“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-citationA 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 77 · see citing works
REGγ deficiency promotes premature aging via the casein kinase 1 pathway
Li, L., Zhao, D., Wei, H., Yao, L., Dang, Y., Amjad, A., Xu, J., Liu, J., Guo, L., Li, D., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1308497110 · Cited by 72 · see citing works
“In contrast to the p53 and p44 mouse models, a “super p53” mouse model, with one or two extra copies of genomic p53 along with flanking regulatory sequences, showed enhanced p53 response to DNA damage, resistance to both spontaneous and carcinogen-induced tumors, but a normal lifespan compared with wild-type mice (9).”
Resultp53: at the crossroad between cancer and ageing
Papazoglu, C., & Mills, A. (2007) · The Journal of Pathology · doi:10.1002/path.2086 · Cited by 73 · see citing works
“In a recent report, the same group showed that, despite an increase in p53 activity in ‘super p53’ mice carrying three functional copies of the p53 gene, telomere-driven ageing is not accelerated on a telomerase-deficient background [33].”
BackgroundBahrami, A., Bo, S., Jamialahmadi, T., & Sahebkar, A. (2020) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101024 · Cited by 67 · see citing works
The p53 tumor suppressor protein is a critical regulator of hematopoietic stem cell behavior
Liu, Y., Elf, S., Asai, T., Miyata, Y., Liu, Y., Sashida, G., Huang, G., Giandomenico, S. D., Koff, A., & Nimer, S. D. (2009) · Cell Cycle · doi:10.4161/cc.8.19.9627 · Cited by 65 · see citing works
“Yet, “super-p53” mice, which have three copies of a wild type p53, have a normal lifespan and show no evidence of early aging.(55) It is likely that the constitutively high p53 activity in the p53/m mice accelerates aging, while the extra copy of p53 in the “super-p53” mice is subject to normal regulation, and thus p5…”
BackgroundSiegl-Cachedenier, I., Flores, I., Klatt, P., & Blasco, M. A. (2007) · The Journal of Cell Biology · doi:10.1083/jcb.200704141 · Cited by 64 · see citing works
“…these defects are anticipated with subsequent Terc−/− mouse generations with progressively shorter telomeres concomitant with premature loss of tissue regeneration and organismal survival (Lee et al., 1998; Herrera et al., 1999; Leri et al., 2003; Flores et al., 2005; García-Cao et al., 2006).”
Self-citationWip1 deficiency impairs haematopoietic stem cell function via p53 and mTORC1 pathways
Chen, Z., Yi, W., Morita, Y., Wang, H., Cong, Y., Liu, J., Xiao, Z., Rudolph, K. L., Cheng, T., & Ju, Z. (2015) · Nature Communications · doi:10.1038/ncomms7808 · Cited by 61 · see citing works
Regulation of Senescence in Cancer and Aging
Kong, Y., Cui, H., Ramkumar, C., & Zhang, H. (2011) · Journal of Aging Research · doi:10.4061/2011/963172 · Cited by 55 · see citing works
“[285] I.”
BackgroundIncreased Arf/p53 activity in stem cells, aging and cancer
Carrasco‐García, E., Moreno, M., Moreno‐Cugnon, L., & Matheu, A. (2017) · Aging Cell · doi:10.1111/acel.12574 · Cited by 51 · see citing works
“…presence of the transgenic p53 or Ink4/Arf allele in mice deficient in telomerase and apolipoprotein E-null mice does not aggravate the accelerated aging or the atherosclerosis-prone characteristic phenotypes of these mice (Garcia-Cao et al., 2006; Sanz-Gonzalez et al., 2007; Fuster et al., 2012).”
BackgroundMartínez, P., Goméz-López, G., Pisano, D. G., Flores, J. M., & Blasco, M. A. (2016) · Aging Cell · doi:10.1111/acel.12517 · Cited by 47 · see citing works
“findings showing a premature loss of mouse survival associated with short telomeres (Herrera et al., 1999; Garcia-Cao et al., 2006).”
BackgroundResultInfluentialSelf-citationTelomeres And Telomerase in Adult Stem Cells and Pluripotent Embryonic Stem Cells
Marión, R. M., & Blasco, M. A. (2010) · Advances in experimental medicine and biology · doi:10.1007/978-1-4419-7037-4_9 · Cited by 42 · see citing works
Self-citationMSH2 deficiency abolishes the anticancer and pro‐aging activity of short telomeres
Martínez, P., Siegl‐Cachedenier, I., Flores, J. M., & Blasco, M. A. (2008) · Aging Cell · doi:10.1111/j.1474-9726.2008.00441.x · Cited by 39 · see citing works
Self-citationTelomere dysfunction and stem cell ageing
Ju, Z., & Rudolph, K. L. (2007) · Biochimie · doi:10.1016/j.biochi.2007.09.006 · Cited by 40 · see citing works
Targeting USP2 regulation of VPRBP-mediated degradation of p53 and PD-L1 for cancer therapy
Yi, J., Tavana, O., Li, H., Wang, D., Baer, R. J., & Gu, W. J. (2023) · Nature Communications · doi:10.1038/s41467-023-37617-3 · Cited by 41 · see citing works
“More specifically, VPRBP bound a GST-fusion protein harboring the C-terminal intracellular domain (ICD, amino acids 231-290), but not theN-terminal (1-119) or middle (120-230) domains, of PD-L1 (Fig.”
BackgroundMicroRNAs in HPV associated cancers: small players with big consequences
Satapathy, S., Batra, J., Jeet, V., Thompson, E. W., & Punyadeera, C. (2017) · Expert Review of Molecular Diagnostics · doi:10.1080/14737159.2017.1339603 · Cited by 37 · see citing works
“Inhibition of E6/E7 oncoproteins leads to induction of senescence along with the restoration of p53 [79,83].”
BackgroundMuñoz-Lorente, M. A., Martínez, P., Tejera, Á., Whittemore, K., Moisés-Silva, A. C., Bosch, F., & Blasco, M. A. (2018) · PLOS Genetics · doi:10.1371/journal.pgen.1007562 · Cited by 40 · see citing works
Self-citationThe relevance of protein-protein interactions for p53 function: the CPE contribution
Fernández-Fernández, M. R., & Sot, B. (2010) · Protein Engineering Design and Selection · doi:10.1093/protein/gzq074 · Cited by 32 · see citing works
“…al., 2009), control of mitochondrial survival proteins (Yu and Zhang, 2003; Moll et al., 2005), microRNA processing (Suzuki et al., 2009), ageing (Garcia-Cao et al., 2002, 2006; Tyner et al., 2002; Maier et al., 2004; Matheu et al., 2007) or in the reprogramming of differentiated cells (Hong et…”
BackgroundStem Cell Ageing and Apoptosis
Fulle, S., Centurione, L., Mancinelli, R., Sancilio, S., Manzoli, F. A., & Pietro, R. D. (2012) · Current Pharmaceutical Design · doi:10.2174/138161212799859657 · Cited by 33 · see citing works
“Furthermore, p53 fl/m HSCs have a lower engraftment capacity than wild-type or p53-null HSCs [230], whereas mice carrying three functional copies of the p53 gene (super-p53) have a normal lifespan but some evidence of early ageing [277].”
BackgroundCell intrinsic and extrinsic mechanisms of stem cell aging depend on telomere status
Song, Z., Ju, Z., & Rudolph, K. L. (2008) · Experimental Gerontology · doi:10.1016/j.exger.2008.06.009 · Cited by 33 · see citing works
“,2002; Donehower, 2002) 2000) Extra copy of naturally regulated p53: no rescue of premature aging (Garcia-Cao et al., 2006)”
BackgroundRemoving all obstacles: A critical role for p53 in promoting tissue renewal
Schoppy, D. W., Ruzankina, Y., & Brown, E. J. (2010) · Cell Cycle · doi:10.4161/cc.9.7.11194 · Cited by 32 · see citing works
Baird, D. M. (2006) · Experimental Gerontology · doi:10.1016/j.exger.2006.09.009 · Cited by 30 · see citing works
CHIP-dependent p53 regulation occurs specifically during cellular senescence
Sisoula, C., Trachana, V., Patterson, C., & Gonos, E. S. (2010) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2010.10.701 · Cited by 28 · see citing works
Aging by Telomere Loss Can Be Reversed
de Jesus, B. B., & Blasco, M. A. (2011) · Cell stem cell · doi:10.1016/j.stem.2010.12.013 · Cited by 24 · see citing works
“…decrease in median and maximum longevity and a higher incidence of agerelated pathologies and stem cell dysfunction compared with wild-type mice (Flores et al., 2005; Garcia-Cao et al., 2006), indicating that, as in humans, telomerase activity is rate limiting for natural mouse longevity and aging.”
BackgroundSelf-citationHuang, Y., Hasegawa, H., Wang, S.-W., Ku, C., Lin, Y., Chiou, S., Hou, M., Wu, D., Tsai, E., Saito, S., et al. (2010) · BioMed Research International · doi:10.1155/2011/569034 · Cited by 23 · see citing works
Function of telomere in aging and age related diseases
Erdem, H. B., Bahsi, T., & Ergün, M. A. (2021) · Environmental Toxicology and Pharmacology · doi:10.1016/j.etap.2021.103641 · Cited by 20 · see citing works
Histone Chaperone Jun Dimerization Protein 2 (JDP2): Role in Cellular Senescence and Aging
Huang, Y., Saito, S., & Yokoyama, K. K. (2010) · The Kaohsiung Journal of Medical Sciences · doi:10.1016/s1607-551x(10)70081-4 · Cited by 19 · see citing works
The Cell Biology of Stem Cells
Meshorer, E., & Plath, K. (2010) · Advances in experimental medicine and biology · doi:10.1007/978-1-4419-7037-4 · Cited by 18 · see citing works
Traditional herbs: mechanisms to combat cellular senescence
Wang, L., Wang, J., Yang, Z., Wang, Y., Zhao, T., Luo, W., Liang, T., & Zheng, Y. (2023) · Aging · doi:10.18632/aging.205269 · Cited by 17 · see citing works
Hartwig, F. P., & Collares, T. V. (2013) · Ageing Research Reviews · doi:10.1016/j.arr.2013.03.003 · Cited by 11 · see citing works
Breaking the aging epigenetic barrier
Sikder, S., Arunkumar, G., Melters, D. P., & Dalal, Y. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.943519 · Cited by 12 · see citing works
The Pivotal Role of One-Carbon Metabolism in Neoplastic Progression During the Aging Process
Majumder, A., Bano, S., & Nayak, K. B. (2024) · Biomolecules · doi:10.3390/biom14111387 · Cited by 11 · see citing works
p53 Modulates the Fate of Cardiac Progenitor Cells Ex Vivo and in the Diabetic Heart In Vivo
Kannappan, R., Matsuda, A., Ferreira‐Martins, J., Zhang, E., Palano, G., Czarna, A., Cabral-da-Silva, M. C., Carvalho, A. B., Sanada, F., Ide, N., et al. (2017) · EBioMedicine · doi:10.1016/j.ebiom.2017.01.028 · Cited by 10 · see citing works
“Male and female wild-type (WT) and super p53 transgenic (p53-tg) mice in a C57BL/6 genetic background were studied (Garcia-Cao et al., 2002, 2006).”
BackgroundSelf-citationNew developments in small molecules targeting p53 pathways in anticancer therapy
Cheok, C. F., & Lane, D. P. (2008) · Drug Development Research · doi:10.1002/ddr.20261 · Cited by 8 · see citing works
“Although the overexpression of p53 in mouse models is also implicated in accelerated aging, reports have demonstrated that p53 can suppress tumor formation without accelerated aging and pharmacological means to activate p53 continues to be an attractive avenue for drug discovery [Garcia-Cao et al., 2006; Gudkov and Ko…”
BackgroundPolonio, A. M., Medrano, M., Chico-Sordo, L., Córdova-Oriz, I., Cozzolino, M., Montáns, J., Herraiz, S., Seli, E. U., Pellicer, A., García-Velasco, J. A., et al. (2023) · Aging · doi:10.18632/aging.204731 · Cited by 9 · see citing works
Lu, Y., Wei, B., Zhang, T., Chen, Z., & Ye, J. (2013) · Protein & Cell · doi:10.1007/s13238-013-3002-4 · Cited by 8 · see citing works
Nakade, K., Lin, C., Chen, X., Tsai, M., Wuputra, K., Zhu, Z., Pan, J., & Yokoyama, K. K. (2017) · FEBS Open Bio · doi:10.1002/2211-5463.12325 · Cited by 6 · see citing works
Senescence Ecology: Aging in a Population of Wild Brown Mouse Lemurs (Microcebus rufus)
Zohdy, S. (2012) · Työväentutkimus Vuosikirja · doi:10.13140/rg.2.1.1825.4881 · Cited by 7 · see citing works
Genetically modified mouse models in cancer studies
Santos, J., Fernández‐Navarro, P., Villa‐Morales, M., González-Sánchez, L., & Fernández‐Piqueras, J. (2008) · Clinical & Translational Oncology · doi:10.1007/s12094-008-0292-8 · Cited by 4 · see citing works
“allowed the team of Manuel Serrano to demonstrate that increased activity of Tp53 does not accelerate telomeredriven ageing [54].”
BackgroundPortillo, A. M., García-Velasco, J. A., & Varela, E. (2024) · Mathematical Biosciences · doi:10.1016/j.mbs.2024.109305 · Cited by 3 · see citing works
Battling cancer on many fronts
Zanella, F., & Carnero, A. (2008) · EMBO Reports · doi:10.1038/embor.2008.140 · Cited by 2 · see citing works
New Insights into P53 Signalling and Cancer: Implications for Cancer Therapy
Nigro, C. L. (2014) · Journal of Tumor · Cited by 2 · see citing works
THE EVOLUTIONARY ECOLOGY OF SENESCENCE The evolution of senescence from a comparative perspective
Ricklefs, R. E. (2008) · Cited by 2 · see citing works
Gutierrez, L. G., & Ju, Z. (2007) · Springer eBooks · doi:10.1007/978-3-540-73709-4_8 · Cited by 2 · see citing works
Cancer, Senescence, and Aging: Translation from Basic Research to Clinics
LLeonart, M. E., Carnero, A., Paciucci, R., Wang, Z., & Shomron, N. (2011) · Journal of Aging Research · doi:10.4061/2011/692301 · Cited by 1 · see citing works
Effect of Mediterranean Diet on Healthy Brain Aging
Boccardi, V., Tinarelli, C., & Mecocci, P. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-811959-4.00006-7 · Cited by 1 · see citing works
Mouse Model: Telomeres and Telomerase in Stem Cell and Cancer
Huang, X., & Ju, Z. (2009) · Humana Press eBooks · doi:10.1007/978-1-60327-879-9_6 · Cited by 1 · see citing works
“However, the increased sensing of telomere dysfunction in super-p53 Terc � /� mice did not lead to a further decrease of lifespan compared to Terc � /� mice ( 80 ).”
BackgroundRole of Jun dimerization protein 2 (JDP2) in cellular senescence
Huang, Y., Lee, I.-L., Tsai, Y.-F., Saito, S., Lin, Y., Chiou, S., Tsai, E., & Yokoyama, K. K. (2010) · Inflammation and Regeneration · doi:10.2492/inflammregen.30.507 · Cited by 1 · see citing works
Replicative Senescence as an Intrinsic Tumor-Suppressor Mechanism
Chang, S. S. (2009) · Springer eBooks · doi:10.1007/978-1-4419-1075-2_8
“These findings are in agreement with genetically engineered mice expressing extra copies of p53 (García-Cao et al. 2006; Mendrysa et al. 2006).”
BackgroundChromatin in Senescent Cells: A Conduit for the Anti-Aging Effects of Wnt Signaling?
Gowrishankar, B., & Adams, P. D. (2009) · Springer eBooks · doi:10.1007/978-1-4419-0639-7_6
Epigenetic regulation of p16 Ink4a and Arf by JDP2 in cellular senescence
Nakade, K., Wasylyk, B., & Yokoyama, K. K. (2010) · BioMolecular Concepts · doi:10.1515/bmc.2010.008
Sénescence cellulaire et cancer: «Le pacte Faustien»
Gaudin, C. (2011) · Springer eBooks · doi:10.1007/978-2-8178-0142-1_3
Mutemwa, M. (2012) · University of the Western Cape Electronic Theses and Dissertations Repository (University of the Western Cape)
Mangalhara, K. C., & Bamezai, R. N. K. (2019) · Springer eBooks · doi:10.1007/978-981-13-3585-3_11
Rizos, H., & Scurr, L. L. (2011) · Springer eBooks · doi:10.1007/978-3-7091-0371-5_11
Rizos, H., Haferkamp, S., & Scurr, L. L. (2017) · Springer eBooks · doi:10.1007/978-3-319-41319-8_11
- 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
- Health Sciences › Medicine › Physiology › 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
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