p21 Both Attenuates and Drives Senescence and Aging in BubR1 Progeroid Mice
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BubR1 insufficiency occurs with natural aging and induces progeroid phenotypes in both mice and children with mosaic variegated aneuploidy syndrome. In response to BubR1 insufficiency, skeletal muscle, fat, and lens tissue engage p19(Arf) to attenuate senescence and age-related deterioration. Here, we address how p19(Arf) exerts this caretaker role using BubR1 progeroid mice lacking p53 or its transcriptional target p21. We show that p53 delays functional decline of skeletal muscle and fat in a p21-dependent fashion by inhibiting p16(Ink4a)-mediated senescence of progenitor cells. Strikingly, p53 also attenuates the formation of cataractous lenses, but here its antiaging effect is p21 independent, as we found p21 to promote senescence of lens epithelial cells and cataract formation. Together, these results demonstrate that p53 counteracts tissue destruction in response to BubR1 insufficiency through diverse mechanisms and uncover a causal link between senescence of the progenitor cell compartment and age-related dysfunction.
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p21 plays a complex role in senescence and aging in BubR1 hypomorphic progeroid mice.
“p21 also plays a complex role in senescence and aging in BubR1 hypomorphic progeroid mice”
From p21 maintains senescent cell viability under persistent DNA damage response by restraining JNK and caspase signaling (2017) · cites this paper as Baker et al, 2013
p21 upregulation protected HSCs against IR by limiting IR-induced DNA damage and p53 activation and by promoting HSC cell cycle entry and self-renewing expansion.
“p21 upregulation actually protected HSCs against IR by limiting IR-induced DNA damage and p53 activation and by promoting HSC cell cycle entry and self-renewing expansion, suggesting that p21 and p16 may have opposite effects on IR-induced HSC senescence.46-48”
From Total body irradiation causes long-term mouse BM injury via induction of HSC premature senescence in an Ink4a- and Arf-independent manner (2014) · cites this paper as [47]
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Cites
Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders
Baker, D. J., Wijshake, T., Tchkonia, T., LeBrasseur, N. K., Childs, B. G., van de Sluis, B., Kirkland, J. L., & van Deursen, J. M. (2011) · Nature · doi:10.1038/nature10600 · Cited by 3,670 · cited 9× · see citing works
“Single-Cell Isolation, Labeling, and Collection Preparation of single cells from inguinal adipose tissue (Baker et al., 2011) and gastrocnemius muscle (Baker et al., 2013) were as previously described.”
InfluentialSelf-citationBlinded by the Light: The Growing Complexity of p53
Vousden, K. H., & Prives, C. (2009) · Cell · doi:10.1016/j.cell.2009.04.037 · Cited by 3,163 · see citing works
Kenyon, C. J. (2010) · Nature · doi:10.1038/nature08980 · Cited by 2,739 · see citing works
Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors
Campisi, J. (2005) · Cell · doi:10.1016/j.cell.2005.02.003 · Cited by 2,359 · cited 2× · see citing works
“Aging is a complex biological process that increases the risk of a broad spectrum of human diseases and disorders, including diabetes, osteoporosis, arthritis, cataracts, sarcopenia, and cardiovascular and neurological disease (Campisi, 2005; Gau et al., 2011; Lotz and Caramés, 2011).”
Vousden, K. H., & Lane, D. P. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2147 · Cited by 2,275 · see citing works
Tumor spectrum analysis in p53-mutant mice
Jacks, T., Remington, L., Williams, B. O., Schmitt, E. M., Halachmi, S., Bronson, R. T., & Weinberg, R. A. (1994) · Current Biology · doi:10.1016/s0960-9822(00)00002-6 · Cited by 2,051 · see citing works
Muscle injury activates resident fibro/adipogenic progenitors that facilitate myogenesis
Joe, A. W. B., Yi, L., Natarajan, A., Le Grand, F., So, L., Wang, J., Rudnicki, M. A., & Rossi, F. M. V. (2010) · Nature Cell Biology · doi:10.1038/ncb2015 · Cited by 1,690 · see citing works
Tumor Suppression at the Mouse INK4a Locus Mediated by the Alternative Reading Frame Product p19
Kamijo, T., Zindy, F., Roussel, M. F., Quelle, D. E., Downing, J. R., Ashmun, R. A., Grosveld, G., & Sherr, C. J. (1997) · Cell · doi:10.1016/s0092-8674(00)80452-3 · Cited by 1,566 · see citing works
Ink4a/Arf expression is a biomarker of aging
Krishnamurthy, J., Torrice, C., Ramsey, M. R., Kovalev, G. I., Al-Regaiey, K., Su, L., & Sharpless, N. E. (2004) · Journal of Clinical Investigation · doi:10.1172/jci22475 · Cited by 1,486 · 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 · cited 3× · see citing works
“…such as Zmpste24 null (a model for Hutchinson-Gilford progeria), Brca1 null, and Ercc1 hypomorphic mice, showing that p53 drives early aging in these models (Cao et al., 2003; Kirkwood, 2002; Maier et al., 2004; Núñez et al., 2000; Sharpless, 2004; Tyner et al., 2002; Varela et al., 2005).”
Radiation-induced cell cycle arrest compromised by p21 deficiency
Brugarolas, J., Chandrasekaran, C., Gordon, J. I., Beach, D., Jacks, T., & Hannon, G. J. (1995) · Nature · doi:10.1038/377552a0 · Cited by 1,242 · cited 4× · see citing works
“, 1994) and p21 (Brugarolas et al., 1995) knockout mice were acquired from The Jackson Laboratory (Bar Harbor, ME, USA).”
InfluentialNotch-Mediated Restoration of Regenerative Potential to Aged Muscle
Conboy, I. M., Conboy, M. J., Smythe, G. M., & Rando, T. A. (2003) · Science · doi:10.1126/science.1087573 · Cited by 1,121 · see citing works
Conboy, I. M., & Rando, T. A. (2002) · Developmental Cell · doi:10.1016/s1534-5807(02)00254-x · Cited by 905 · see citing works
Regulation ofp53downstream genes
El‐Deiry, W. S. (1998) · Seminars in Cancer Biology · doi:10.1006/scbi.1998.0097 · Cited by 797 · see citing works
BubR1 insufficiency causes early onset of aging-associated phenotypes and infertility in mice
Baker, D. J., Jeganathan, K. B., Cameron, J. D., Thompson, M., Juneja, S., Kopecka, A., Kumar, R., Jenkins, R. B., de Groen, P. C., Roche, P., et al. (2004) · Nature Genetics · doi:10.1038/ng1382 · Cited by 731 · see citing works
Self-citationConstitutional aneuploidy and cancer predisposition caused by biallelic mutations in BUB1B
Hanks, S., Coleman, K., Reid, S., Plaja, A., Firth, H., Fitzpatrick, D., Kidd, A., Méhes, K., Nash, R., Robin, N. H., et al. (2004) · Nature Genetics · doi:10.1038/ng1449 · Cited by 627 · 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
Telomeres Acquire Embryonic Stem Cell Characteristics in Induced Pluripotent Stem Cells
Marión, R. M., Strati, K., Li, H., Tejera, Á. M., Schoeftner, S., Ortega, S., Serrano, M., & Blasco, M. A. (2009) · Cell stem cell · doi:10.1016/j.stem.2008.12.010 · Cited by 509 · see citing works
Delayed 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
Accelerated ageing in mice deficient in Zmpste24 protease is linked to p53 signalling activation
Varela, I., Cadiñanos, J., Pendás, A. M., Gutiérrez-Fernández, A., Folgueras, A. R., Sánchez, L. M., Zhou, Z., Rodríguez, F. J., Stewart, C. L., Vega, J. A., et al. (2005) · Nature · doi:10.1038/nature04019 · Cited by 466 · see citing works
Maintenance of muscle stem-cell quiescence by microRNA-489
Cheung, T. H., Quach, N. L., Charville, G. W., Liu, L., Park, L., Edalati, A., Yoo, B., Hoang, P., & Rando, T. A. (2012) · Nature · doi:10.1038/nature10834 · Cited by 461 · see citing works
Adipose tissue stem cells meet preadipocyte commitment: going back to the future
Cawthorn, W. P., Scheller, E. L., & MacDougald, O. A. (2011) · Journal of Lipid Research · doi:10.1194/jlr.r021089 · Cited by 440 · see citing works
Choudhury, A. R., Ju, Z., Djojosubroto, M. W., Schienke, A., Lechel, A., Schaetzlein, S., Jiang, H., Stepczynska, A., Wang, C., Buer, J., et al. (2007) · Nature Genetics · doi:10.1038/ng1937 · Cited by 426 · cited 1× · see citing works
“Second, it has been reported that p21 drives cellular senescence and age-related pathology in a progeroid mouse model for telomere dysfunction (Choudhury et al., 2007).”
Opposing roles for p16Ink4a and p19Arf in senescence and ageing caused by BubR1 insufficiency
Baker, D. J., Perez-Terzic, C., Jin, F., Pitel, K. S., Niederländer, N. J., Jeganathan, K., Yamada, S., Reyes, S., Rowe, L., Hiddinga, H. J., et al. (2008) · Nature Cell Biology · doi:10.1038/ncb1744 · Cited by 408 · cited 22× · see citing works
“Analysis of Progeroid Phenotypes Biweekly checks for lordokyphosis and cataracts were as previously described (Baker et al., 2008b).”
InfluentialSelf-citationProgeria syndromes and ageing: what is the connection?
Burtner, C. R., & Kennedy, B. K. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2944 · Cited by 386 · see citing works
Kasper, L. H., Brindle, P. K., Schnabel, C., Pritchard, C., Cleary, M., & van Deursen, J. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.1.764 · Cited by 357 · see citing works
Babu, J. R., Jeganathan, K. B., Baker, D. J., Wu, X., Kang, N., & van Deursen, J. M. (2003) · The Journal of Cell Biology · doi:10.1083/jcb.200211048 · Cited by 342 · see citing works
Self-citationMinagawa, S., Araya, J., Numata, T., Nojiri, S., Hara, H., Yumino, Y., Kawaishi, M., Odaka, M., Morikawa, T., Nishimura, S. L., et al. (2011) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00097.2010 · Cited by 323 · see citing works
Autophagy and cartilage homeostasis mechanisms in joint health, aging and OA
Lotz, M. K., & Caramés, B. (2011) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2011.109 · Cited by 314 · cited 2× · see citing works
“Aging is a complex biological process that increases the risk of a broad spectrum of human diseases and disorders, including diabetes, osteoporosis, arthritis, cataracts, sarcopenia, and cardiovascular and neurological disease (Campisi, 2005; Gau et al., 2011; Lotz and Caramés, 2011).”
Cao, L., Li, W., Kim, S., Brodie, S. G., & Deng, C.-X. (2003) · Genes & Development · doi:10.1101/gad.1050003 · Cited by 293 · see citing works
Increased expression of BubR1 protects against aneuploidy and cancer and extends healthy lifespan
Baker, D. J., Dawlaty, M. M., Wijshake, T., Jeganathan, K. B., Malureanu, L. A., van Ree, J. H., Crespo‐Diaz, R. J., Reyes, S., Seaburg, L., Shapiro, V. S., et al. (2012) · Nature Cell Biology · doi:10.1038/ncb2643 · Cited by 272 · see citing works
Self-citationFeng, Z., Hu, W., Teresky, A. K., Hernando, E., Cordon-Cardo, C., & Levine, A. J. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0708043104 · Cited by 264 · see citing works
Statistical methods for testing effects on “maximum lifespan”
Wang, C., Li, Q., Redden, D. T., Weindruch, R., & Allison, D. B. (2004) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2004.07.003 · Cited by 208 · see citing works
Matsuura, S., Matsumoto, Y., Morishima, K., Izumi, H., Matsumoto, H., Ito, E., Tsutsui, K., Kobayashi, J., Tauchi, H., Kajiwara, Y., et al. (2006) · American Journal of Medical Genetics. Part A · doi:10.1002/ajmg.a.31069 · Cited by 179 · see citing works
Early aging–associated phenotypes in Bub3/Rae1 haploinsufficient mice
Baker, D. J., Jeganathan, K. B., Malureanu, L., Perez-Terzic, C., Terzic, A., & van Deursen, J. M. A. (2006) · The Journal of Cell Biology · doi:10.1083/jcb.200507081 · Cited by 175 · see citing works
Self-citationIsolation of p53‐target genes and their functional analysis
Nakamura, Y. (2004) · Cancer Science · doi:10.1111/j.1349-7006.2004.tb03163.x · Cited by 169 · see citing works
Ink4a/Arf links senescence and aging
Sharpless, N. E. (2004) · Experimental Gerontology · doi:10.1016/j.exger.2004.06.025 · Cited by 142 · see citing works
Suijkerbuijk, S. J. E., van Osch, M. H. J., Bos, F. L., Hanks, S., Rahman, N., & Kops, G. J. P. L. (2010) · Cancer Research · doi:10.1158/0008-5472.can-09-4319 · Cited by 125 · see citing works
Homozygous BUB1B Mutation and Susceptibility to Gastrointestinal Neoplasia
Frio, T. R., Lavoie, J., Hamel, N., Geyer, F. C., Kushner, Y. B., Novak, D. J., Wark, L., Capelli, C., Reis-Filho, J. S., Mai, S., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1006565 · Cited by 92 · see citing works
Aging-Associated Vascular Phenotype in Mutant Mice With Low Levels of BubR1
Matsumoto, T., Baker, D. J., d’Uscio, L. V., Mozammel, G., Katusic, Z. S., & van Deursen, J. M. (2007) · Stroke · doi:10.1161/01.str.0000257967.86132.01 · Cited by 77 · see citing works
Self-citationp53: 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
Núñez, F., Chipchase, M. D., Clarke, A. R., & Melton, D. W. (2000) · The FASEB Journal · doi:10.1096/fasebj.14.9.1073 · Cited by 68 · see citing works
Reduced Life- and Healthspan in Mice Carrying a Mono-Allelic BubR1 MVA Mutation
Wijshake, T., Malureanu, L. A., Baker, D. J., Jeganathan, K. B., van de Sluis, B., & van Deursen, J. M. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1003138 · Cited by 59 · see citing works
Self-citationThe yin and yang of the Cdkn2a locus in senescence and aging
Baker, D. J., Jin, F., & van Deursen, J. M. (2008) · Cell Cycle · doi:10.4161/cc.7.18.6687 · Cited by 56 · cited 22× · see citing works
“Analysis of Progeroid Phenotypes Biweekly checks for lordokyphosis and cataracts were as previously described (Baker et al., 2008b).”
MethodInfluentialSelf-citationMutant mice with small amounts of BubR1 display accelerated age-related gliosis
Hartman, T. K., Wengenack, T. M., Poduslo, J. F., & van Deursen, J. M. (2007) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2006.05.012 · Cited by 54 · see citing works
Mosaic variegated aneuploidy with growth hormone deficiency and congenital heart defects
Lane, A., Aijaz, N. J., Galvin‐Parton, P., Lanman, J. T., Mangano, R., & Wilson, T. A. (2002) · American Journal of Medical Genetics · doi:10.1002/ajmg.10462 · Cited by 26 · see citing works
p53 and ageing: too much of a good thing?
Kirkwood, T. B. L. (2002) · BioEssays · doi:10.1002/bies.10111 · Cited by 19 · see citing works
Gau, P., Rodriguez, S., Leonardis, C. D., Chen, P., & Lin, D. M. (2010) · Gene Therapy · doi:10.1038/gt.2010.153 · Cited by 12 · see citing works
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Naturally occurring p16Ink4a-positive cells shorten healthy lifespan
Baker, D. J., Childs, B. G., Durik, M., Wijers, M. E., Sieben, C. J., Zhong, J., A. Saltness, R., Jeganathan, K. B., Verzosa, G. C., Pezeshki, A., et al. (2016) · Nature · doi:10.1038/nature16932 · Cited by 2,891 · see citing works
“…from iWAT, collected the stromal vascular fraction by centrifugation and labelled the resulting cells with specific cell surface markers for collection of the CD45 + , endothelial, and progenitor (adipocyte stem cells + preadipocytes) cell populations by FACS as previously described 4, 35, 37 .”
Self-citationThe role of senescent cells in ageing
van Deursen, J. M. (2014) · Nature · doi:10.1038/nature13193 · Cited by 2,623 · see citing works
Cellular senescence in aging and age-related disease: from mechanisms to therapy
Childs, B. G., Durik, M., Baker, D. J., & van Deursen, J. M. (2015) · Nature Medicine · doi:10.1038/nm.4000 · Cited by 2,363 · see citing works
Self-citationSenescent cells: an emerging target for diseases of ageing
Childs, B. G., Gluscevic, M., Baker, D. J., Laberge, R.-M., Marquess, D., Dananberg, J., & van Deursen, J. M. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.116 · Cited by 1,284 · see citing works
Self-citationGeriatric muscle stem cells switch reversible quiescence into senescence
Sousa-Victor, P., Gutarra, S., García-Prat, L., Rodriguez-Ubreva, J., Ortet, L., Ruiz-Bonilla, V., Jardí, M., Ballestar, E., González, S., Serrano, A. L., et al. (2014) · Nature · doi:10.1038/nature13013 · Cited by 1,010 · see citing works
Senescence and apoptosis: dueling or complementary cell fates?
Childs, B. G., Baker, D. J., Kirkland, J. L., Campisi, J., & van Deursen, J. M. (2014) · The EMBO Reports · doi:10.15252/embr.201439245 · Cited by 915 · see citing works
Self-citationIdentification of senescent cells in the bone microenvironment
Farr, J. N., Fraser, D. G., Wang, H., Jaehn, K., Ogrodnik, M. B., Weivoda, M. M., Drake, M. T., Tchkonia, T., LeBrasseur, N. K., Kirkland, J. L., et al. (2016) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.2892 · Cited by 562 · see citing works
Recurrent turnover of senescent cells during regeneration of a complex structure
Yun, M. H., Davaapil, H., & Brockes, J. P. (2015) · eLife · doi:10.7554/elife.05505 · Cited by 385 · see citing works
Cellular senescence in osteoarthritis pathology
McCulloch, K., Litherland, G. J., & Rai, T. S. (2017) · Aging Cell · doi:10.1111/acel.12562 · Cited by 367 · see citing works
Liu, J.-Y., Souroullas, G. P., Diekman, B. O., Krishnamurthy, J., Hall, B. M., Sorrentino, J. A., Parker, J. S., Sessions, G. A., Gudkov, A. V., & Sharpless, N. E. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1818313116 · Cited by 306 · see citing works
Yosef, R., Pilpel, N., Papismadov, N., Gal, H., Ovadya, Y., Vadai, E., Miller, S., Porat, Z., Ben‐Dor, S., & Krizhanovsky, V. (2017) · The EMBO Journal · doi:10.15252/embj.201695553 · Cited by 293 · see citing works
The Molecular Balancing Act of p16INK4a in Cancer and Aging
LaPak, K. M., & Burd, C. E. (2013) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-13-0350 · Cited by 294 · see citing works
DNA damage response and metabolic disease
Shimizu, I., Yoshida, Y., Suda, M., & Minamino, T. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.10.008 · Cited by 286 · see citing works
Astrocyte senescence: Evidence and significance
Cohen, J., & Torres, C. (2019) · Aging Cell · doi:10.1111/acel.12937 · Cited by 281 · see citing works
Zhu, Y., Liu, X., Ding, X., Wang, F., & Geng, X. (2019) · Biogerontology · doi:10.1007/s10522-018-9769-1 · Cited by 255 · see citing works
Aneuploidy and chromosomal instability in cancer: a jackpot to chaos
Giam, M., & Rancati, G. I. (2015) · Cell Division · doi:10.1186/s13008-015-0009-7 · Cited by 246 · see citing works
Senescent cells: SASPected drivers of age-related pathologies
Ovadya, Y., & Krizhanovsky, V. (2014) · Biogerontology · doi:10.1007/s10522-014-9529-9 · Cited by 232 · see citing works
Age-related inflammation triggers skeletal stem/progenitor cell dysfunction
Josephson, A. M., Bradaschia-Corrêa, V., Lee, S., Leclerc, K., Patel, K. S., Muiños-López, E., Litwa, H. P., Neibart, S. S., Kadiyala, M. L., Wong, M. Z., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1810692116 · Cited by 205 · see citing works
Impact of genomic damage and ageing on stem cell function
Behrens, A., van Deursen, J. M., Rudolph, K. L., & Schumacher, B. (2014) · Nature Cell Biology · doi:10.1038/ncb2928 · Cited by 207 · see citing works
Vascular senescence in cardiovascular and metabolic diseases
Katsuumi, G., Shimizu, I., Yoshida, Y., & Minamino, T. (2018) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2018.00018 · Cited by 196 · see citing works
Aneuploidy as a promoter and suppressor of malignant growth
Vasudevan, A., Schukken, K. M., Sausville, E. L., Girish, V., Adebambo, O. A., & Sheltzer, J. M. (2021) · Nature reviews. Cancer · doi:10.1038/s41568-020-00321-1 · Cited by 176 · see citing works
Senescence in Wound Repair: Emerging Strategies to Target Chronic Healing Wounds
Wilkinson, H. N., & Hardman, M. J. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00773 · Cited by 173 · see citing works
Shao, L., Feng, W., Li, H., Gardner, D., Luo, Y., Wang, Y., Liu, L., Meng, A., Sharpless, N. E., & Zhou, D. (2014) · Blood · doi:10.1182/blood-2013-07-515619 · Cited by 165 · see citing works
Experimental Models of Sarcopenia: Bridging Molecular Mechanism and Therapeutic Strategy
Mankhong, S., Kim, S., Moon, S., Kwak, H., Park, D., & Kang, J. (2020) · Cells · doi:10.3390/cells9061385 · Cited by 144 · see citing works
Cellular senescence links aging and diabetes in cardiovascular disease
Shakeri, H., Lemmens, K., Gevaert, A. B., De Meyer, G. R. Y., & Segers, V. F. M. (2018) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00287.2018 · Cited by 134 · see citing works
Murakami, T., Inagaki, N., & Kondoh, H. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.869414 · Cited by 134 · see citing works
Chandra, A., Lagnado, A. B., Farr, J. N., Doolittle, M., Tchkonia, T., Kirkland, J. L., LeBrasseur, N. K., Robbins, P. D., Niedernhofer, L. J., Ikeno, Y., et al. (2022) · Aging Cell · doi:10.1111/acel.13602 · Cited by 120 · see citing works
4-hydroxynonenal-mediated signaling and aging
Zhang, H., & Forman, H. J. (2017) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.11.032 · Cited by 114 · see citing works
Mouse Models to Disentangle the Hallmarks of Human Aging
Folgueras, A. R., Freitas-Rodríguez, S., Velasco, G., & López-Otín, C. (2018) · Circulation Research · doi:10.1161/circresaha.118.312204 · Cited by 113 · see citing works
Molecular basis of ageing in chronic metabolic diseases
Spinelli, R., Parrillo, L., Longo, M., Florese, P., Desiderio, A., Zatterale, F., Miele, C., Raciti, G. A., & Bèguinot, F. (2020) · Journal of Endocrinological Investigation · doi:10.1007/s40618-020-01255-z · Cited by 100 · see citing works
Loss of MT1-MMP causes cell senescence and nuclear defects which can be reversed by retinoic acid
Gutiérrez‐Fernández, A., Soria‐Valles, C., Osorio, F. G., Gutiérrez‐Abril, J., Garabaya, C., Aguirre, A., Fueyo, A., Fernández‐García, M. S., Puente, X. S., & López‐Otín, C. (2015) · The EMBO Journal · doi:10.15252/embj.201490594 · Cited by 96 · see citing works
NF-κB activation impairs somatic cell reprogramming in ageing
Soria‐Valles, C., Osorio, F. G., Gutiérrez‐Fernández, A., Angeles, A. D. L., Bueno, C., Menéndez, P. R., Martín-Subero, J. I., Daley, G. Q., Freije, J. M. P., & López-Otı́n, C. (2015) · Nature Cell Biology · doi:10.1038/ncb3207 · Cited by 95 · see citing works
RetractedHIV-associated cellular senescence: A contributor to accelerated aging
Cohen, J., & Torres, C. A. (2016) · Ageing Research Reviews · doi:10.1016/j.arr.2016.12.004 · Cited by 87 · see citing works
Postnatal 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 85 · see citing works
Emerging insights in senescence: pathways from preclinical models to therapeutic innovations
Mansfield, L., Ramponi, V., Gupta, K., Stevenson, T., Mathew, A. B., Barinda, A. J., Herbstein, F., & Morsli, S. (2024) · npj Aging · doi:10.1038/s41514-024-00181-1 · Cited by 91 · see citing works
Effects of Age and Estrogen on Skeletal Gene Expression in Humans as Assessed by RNA Sequencing
Farr, J. N., Roforth, M. M., Fujita, K., Nicks, K. M., Cunningham, J. M., Atkinson, E. J., Therneau, T. M., McCready, L. K., Peterson, J. M., Drake, M. T., et al. (2015) · PLOS ONE · doi:10.1371/journal.pone.0138347 · Cited by 75 · see citing works
Aging of the eye: Lessons from cataracts and age-related macular degeneration
Cvekl, A., & Vijg, J. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102407 · Cited by 76 · see citing works
Matsuyama, M., Tanaka, H., Inoko, A., Goto, H., Yonemura, S., Kobori, K., Hayashi, Y., Kondo, E., Itohara, S., Izawa, I., et al. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.514737 · Cited by 70 · see citing works
Neuregulin-1 attenuates stress-induced vascular senescence
Shakeri, H., Gevaert, A. B., Schrijvers, D. M., Meyer, G. R. Y. D., Keulenaer, G. W. D., Guns, P., Lemmens, K., & Segers, V. F. M. (2018) · Cardiovascular Research · doi:10.1093/cvr/cvy059 · Cited by 70 · see citing works
Comparison of mice with accelerated aging caused by distinct mechanisms
Gurkar, A. U., & Niedernhofer, L. J. (2015) · Experimental Gerontology · doi:10.1016/j.exger.2015.01.045 · Cited by 70 · see citing works
Colaianni, G., Errede, M., Sanesi, L., Notarnicola, A., Celi, M., Zerlotin, R., Storlino, G., Pignataro, P., Oranger, A., Pesce, V., et al. (2020) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.4192 · Cited by 69 · see citing works
Geroconversion of aged muscle stem cells under regenerative pressure
Sousa-Victor, P., Perdiguero, E., & Muñoz-Cánoves, P. (2014) · Cell Cycle · doi:10.4161/15384101.2014.965072 · Cited by 68 · see citing works
Roles of Apoptosis and Cellular Senescence in Cancer and Aging
Cerella, C., Grandjenette, C., Dicato, M. A., & Diederich, M. F. (2016) · Current Drug Targets · doi:10.2174/1389450116666150202155915 · Cited by 60 · see citing works
Accelerating aging research: How can we measure the rate of biologic aging?
Margolick, J. B., & Ferrucci, L. (2015) · Experimental Gerontology · doi:10.1016/j.exger.2015.02.009 · Cited by 58 · see citing works
p21 can be a barrier to ferroptosis independent of p53
Venkatesh, D., Stockwell, B. R., & Prives, C. L. (2020) · Aging · doi:10.18632/aging.103961 · Cited by 57 · see citing works
Chromosome organisation during ageing and senescence
Chandra, T., & Kirschner, K. (2016) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2016.03.020 · Cited by 57 · see citing works
Tanaka, H., Goto, H., Inoko, A., Makihara, H., Enomoto, A., Horimoto, K., Matsuyama, M., Kurita, K., Izawa, I., & Inagaki, M. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.633891 · Cited by 55 · see citing works
Dethlefsen, M. M., Halling, J. F., Møller, H. D., Plomgaard, P., Regenberg, B., Ringholm, S., & Pilegaard, H. (2018) · Experimental Gerontology · doi:10.1016/j.exger.2018.07.011 · Cited by 54 · see citing works
Sasaki, T., Lian, S., Qi, J., Bayliss, P. E., Carr, C. E., Johnson, J. L., Guha, S., Kobler, P., Catz, S. D., Gill, M. S., et al. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004409 · Cited by 54 · see citing works
Siddam, A. D., Gautier‐Courteille, C., Pérez-Campos, L., Anand, D., Kakrana, A., Dang, C. A., Legagneux, V., Méreau, A., Viet, J., Gross, J. M., et al. (2018) · PLoS Genetics · doi:10.1371/journal.pgen.1007278 · Cited by 54 · see citing works
Increased 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
Hamada, N., & FUJIMICHI, Y. (2015) · Cancer Letters · doi:10.1016/j.canlet.2015.02.017 · Cited by 51 · see citing works
Diverse Roles of Cellular Senescence in Skeletal Muscle Inflammation, Regeneration, and Therapeutics
Saito, Y., & Chikenji, T. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.739510 · Cited by 48 · see citing works
Mouse Models of Accelerated Cellular Senescence
Yousefzadeh, M. J., Melos, K. I., Angelini, L. A., Burd, C. E., Robbins, P. D., & Niedernhofer, L. J. (2018) · Methods in molecular biology · doi:10.1007/978-1-4939-8931-7_17 · Cited by 47 · see citing works
FUJIMICHI, Y., & Hamada, N. (2014) · PLoS ONE · doi:10.1371/journal.pone.0098154 · Cited by 46 · see citing works
A tale of the good and bad: Cell senescence in bone homeostasis and disease
Liu, X., & Wan, M. (2019) · International review of cytology · doi:10.1016/bs.ircmb.2019.03.005 · Cited by 44 · see citing works
Insights from In Vivo Studies of Cellular Senescence
Prieto, L. I., Graves, S. I., & Baker, D. J. (2020) · Cells · doi:10.3390/cells9040954 · Cited by 41 · see citing works
Self-citationAtamna, H., Atamna, W., Al-Eyd, G., Shanower, G., & Dhahbi, J. M. (2015) · Redox Biology · doi:10.1016/j.redox.2015.09.004 · Cited by 40 · see citing works
Marthandan, S., Menzel, U., Priebe, S., Groth, M., Guthke, R., Platzer, M., Hemmerich, P., Kaether, C., & Diekmann, S. (2016) · Biological Research · doi:10.1186/s40659-016-0095-2 · Cited by 39 · see citing works
Hart, C. R., Ryan, Z. C., Pfaffenbach, K. T., Dasari, S., Parvizi, M., Lalia, A. Z., & Lanza, I. R. (2019) · Aging · doi:10.18632/aging.102273 · Cited by 39 · see citing works
Talmasov, D., Zhang, X., Yu, B., Nandan, M. O., Bialkowska, A. B., Elkarim, E. A., Kuruvilla, J., Yang, V. W., & Ghaleb, A. M. (2014) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00080.2014 · Cited by 38 · see citing works
Single-Cell RNA-Sequencing Reveals the Skeletal Cellular Dynamics in Bone Repair and Osteoporosis
Wu, S., Ohba, S., & Matsushita, Y. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24129814 · Cited by 35 · see citing works
Carrasco‐García, E., Arrizabalaga, O., Serrano, M., Lovell-Badge, R. H., & Matheu, A. (2015) · Aging Cell · doi:10.1111/acel.12343 · Cited by 34 · see citing works
Context‐dependent roles of cellular senescence in normal, aged, and disease states
Moiseeva, V., Cisneros, A., Cobos, A. C., Tarrega, A. B., Oñate, C. S., Perdiguero, E., Serrano, A. L., & Muñoz‐Cánoves, P. (2023) · The FEBS Journal · doi:10.1111/febs.16573 · Cited by 34 · see citing works
Micro(RNA)-managing muscle wasting
Sannicandro, A. J., Soriano‐Arroquia, A., & Goljanek‐Whysall, K. (2019) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00961.2018 · Cited by 32 · see citing works
The aging mouse lens transcriptome
Faranda, A. P., Shihan, M. H., Wang, Y., & Duncan, M. K. (2021) · Experimental Eye Research · doi:10.1016/j.exer.2021.108663 · Cited by 33 · see citing works
CINcere Modelling: What Have Mouse Models for Chromosome Instability Taught Us?
Simon, J. E., Bakker, B., & Foijer, F. (2015) · Recent results in cancer research/Recent Results in Cancer Research · doi:10.1007/978-3-319-20291-4_2 · Cited by 31 · see citing works
Connecting the dots: Neuronal senescence, stress granules, and neurodegeneration
Ma, Y., & Farny, N. G. (2023) · Gene · doi:10.1016/j.gene.2023.147437 · Cited by 30 · see citing works
Pereira, S. M., Ribeiro, R., & Logarinho, E. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20040938 · Cited by 30 · see citing works
Sieben, C. J., Jeganathan, K. B., Nelson, G. G., Sturmlechner, I., Zhang, C., van Deursen, W. H., Bakker, B., Foijer, F., Li, H., Baker, D. J., et al. (2019) · Journal of Clinical Investigation · doi:10.1172/jci126863 · Cited by 30 · see citing works
Self-citationKwon, H. Y., Kim, J., Kim, B., Srivastava, S., & Kim, S. (2017) · Archives of Toxicology · doi:10.1007/s00204-017-2021-y · Cited by 29 · see citing works
Xu, X., Li, G., Zhang, D., Zhu, H., Liu, G., & Zhang, Z. (2023) · Advanced Science · doi:10.1002/advs.202205346 · Cited by 29 · see citing works
p21 regulates expression of ECM components and promotes pulmonary fibrosis via CDK4 and Rb
Papismadov, N., Levi, N., Roitman, L., Agrawal, A., Ovadya, Y., Cherqui, U., Yosef, R., Akiva, H., Gal, H., & Krizhanovsky, V. (2024) · The EMBO Journal · doi:10.1038/s44318-024-00246-7 · Cited by 30 · see citing works
Grabliauskaite, K., Hehl, A. B., Seleznik, G. M., Saponara, E., Schlesinger, K., Zuellig, R. A., Dittmann, A., Bain, M., Reding, T., Sonda, S., et al. (2015) · The Journal of Pathology · doi:10.1002/path.4440 · Cited by 27 · see citing works
Molecular constraints of sarcopenia in the ageing muscle
Damanti, S., Senini, E., LORENZO, R. D., Merolla, A., Santoro, S., Festorazzi, C., Messina, M., Vitali, G., Sciorati, C., Manfredi, A. A., et al. (2025) · Frontiers in Aging · doi:10.3389/fragi.2025.1588014 · Cited by 30 · see citing works
Effects of Ginger (Zingiber officinale) on the Hallmarks of Aging
Matin, M., Joshi, T., Wang, D., Tzvetkov, N. T., Matin, F. B., Wierzbicka, A., Jóźwik, A., Horbańczuk, J. O., & Atanasov, A. G. (2024) · Biomolecules · doi:10.3390/biom14080940 · Cited by 25 · see citing works
INK4a/ARF Expression Impairs Neurogenesis in the Brain of Irradiated Mice
Lê, O., Palacio, L., Bernier, G., Batinic̈‐Haberle, I., Hickson, G. R. X., & Beausejour, C. M. (2018) · Stem Cell Reports · doi:10.1016/j.stemcr.2018.03.025 · Cited by 25 · see citing works
Su, X., Yao, X., Sun, Z., Han, Q., & Zhao, R. C. (2016) · Stem Cells and Development · doi:10.1089/scd.2016.0031 · Cited by 22 · see citing works
Deficiency of Yes-Associated Protein Induces Cataract in Mice
He, Q., Gao, Y., Wang, T., Zhou, L., Zhou, W., & Yuan, Z. (2018) · Aging and Disease · doi:10.14336/ad.2018.0910 · Cited by 21 · see citing works
Mihailidou, C., Chatzistamou, I., Papavassiliou, A. G., & Kiaris, H. (2016) · Antioxidants and Redox Signaling · doi:10.1089/ars.2016.6671 · Cited by 20 · see citing works
Speeding up the clock: The past, present and future of progeria
Swahari, V., & Nakamura, A. (2015) · Development Growth & Differentiation · doi:10.1111/dgd.12251 · Cited by 20 · see citing works
Senescence in RASopathies, a possible novel contributor to a complex pathophenoype
Engler, M., Fidan, M., Nandi, S., & Cirstea, I. C. (2020) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2020.111411 · Cited by 15 · see citing works
Model Systems to Study the Mechanism of Vascular Aging
van der Linden, J., Trap, L., Scherer, C. V., Roks, A. J. M., Danser, A. H. J., van der Pluijm, I., & Cheng, C. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242015379 · Cited by 17 · see citing works
A novel in vitro model of sarcopenia using BubR1 hypomorphic C2C12 myoblasts
Nozaki, T., Nikai, S., Okabe, R., Nagahama, K., & Eto, N. (2015) · Cytotechnology · doi:10.1007/s10616-015-9920-7 · Cited by 17 · see citing works
Kishi, S., Bayliss, P. E., & Hanai, J. (2014) · Translational research · doi:10.1016/j.trsl.2014.05.007 · Cited by 17 · see citing works
Impact of 10‐day bed rest on serum levels of irisin and markers of musculoskeletal metabolism
Oranger, A., Storlino, G., Dicarlo, M., Zerlotin, R., Pignataro, P., Sanesi, L., Narici, M. V., Pišot, R., Šimunič, B., Colaianni, G., et al. (2022) · The FASEB Journal · doi:10.1096/fj.202201005rr · Cited by 16 · see citing works
Goulart-Filho, J. A. V., Montalli, V. Â. M., Passador‐Santos, F., de Araújo, N. S., & de Araújo, V. C. (2019) · Diagnostic Pathology · doi:10.1186/s13000-019-0796-2 · Cited by 16 · see citing works
p21 facilitates chronic lung inflammation via epithelial and endothelial cells
Levi, N., Papismadov, N., Majewska, J., Roitman, L., Wigoda, N., Eilam, R., Tsoory, M., Rotkopf, R., Ovadya, Y., Akiva, H., et al. (2023) · Aging · doi:10.18632/aging.204622 · Cited by 15 · see citing works
Aging of the Liver: What This Means for Patients with HIV
Chan, A. W., Patel, Y. A., & Choi, S. S. (2016) · Current HIV/AIDS Reports · doi:10.1007/s11904-016-0332-x · Cited by 14 · see citing works
Cui, X., Du, C., Wan, S., Wu, D., Yan, L., Zhang, J., Li, J., Li, H., Yang, Z., Zhang, H., et al. (2021) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2021.166233 · Cited by 15 · see citing works
Montano, M. A., Bhasin, S., D’Aquila, R. T., Erlandson, K. M., Evans, W. J., Funderburg, N., Justice, A. C., Ndhlovu, L. C., Ojikutu, B. O., Pahor, M., et al. (2019) · AIDS Research and Human Retroviruses · doi:10.1089/aid.2019.0130 · Cited by 14 · see citing works
Ye, D., Xu, Y., Shi, Y., Ji, J., Lü, X., Chen, H., Huang, R., Lü, P., Li, Y., Cheng, L. Y., et al. (2022) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.63.1.34 · Cited by 14 · see citing works
Mu, X., Lin, C.-Y., Hambright, W. S., Tang, Y. M., Ravuri, S. K., Lu, A., Matre, P. R., Chen, W., Gao, X., Cui, Y., et al. (2020) · Aging · doi:10.18632/aging.202413 · Cited by 14 · see citing works
The Emerging Role of p21 in Diabetes and Related Metabolic Disorders
ElMitwalli, O. S., Darwish, R., Al-Jabery, L., Algahiny, A. T., Roy, S., Butler, A. E., & Hasan, A. S. H. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252313209 · Cited by 17 · see citing works
Xue, Y., Chen, H., Zhang, S., Bao, L., Chen, B., Gong, H., Zhao, Y., & Qi, R. (2021) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2021/8819231 · Cited by 13 · see citing works
Pluripotent Stem Cells and DNA Damage Response to Ionizing Radiations
Mujoo, K., Butler, E. B., PANDITA, R. K., Hunt, C. R., & Pandita, T. K. (2016) · Radiation Research · doi:10.1667/rr14417.1 · Cited by 12 · see citing works
BubR1 and SIRT2: Insights into aneuploidy, aging, and cancer
Pun, R., Kumari, N., Monieb, R. H., Wagh, S., & North, B. J. (2024) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2024.10.005 · Cited by 10 · see citing works
Senescent cells in the development of cardiometabolic disease
Postmus, A. C., Sturmlechner, I., Jonker, J. W., van Deursen, J. M., van de Sluis, B., & Kruit, J. K. (2019) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000602 · Cited by 10 · see citing works
Accelerated Aging in Cyclophilin B–Deficient Mice Downstream of p21‐Cip1 /Waf1
Zhang, Y., Pignolo, R. J., & Bram, R. J. (2022) · JBMR Plus · doi:10.1002/jbm4.10674 · Cited by 9 · see citing works
Takeshita, H., Yamamoto, K. I., Mogi, M., Wang, Y., Nozato, Y., Fujimoto, T., Yokoyama, S., Hongyo, K., Nakagami, F., Akasaka, H., et al. (2021) · Journal of the American Heart Association · doi:10.1161/jaha.120.021030 · Cited by 6 · see citing works
- Authors
- Baker, D. J., Weaver, R. L., & van Deursen, J. M.
- Affiliations
- Mayo Clinic (US)
- ORCID
- Baker, Darren J.
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2013-04
- Volume
- 3
- Issue
- 4
- Pages
- 1164-1174
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC3785294
- OpenAlex
- W2066844712
- Cited by
- 130
- References
- 48
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 8 · 2023: 5 · 2022: 8 · 2021: 6 · 2020: 12 · 2019: 14 · 2018: 11 · 2017: 6 · 2016: 14 · 2015: 18 · 2014: 14 · 2013: 3
- FWCI
- 11.37
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion, other-oa)
- Funders
- Ellison Medical Foundation
- Mayo Clinic
- National Institutes of Health
- National Institute on Aging (AG-41122, P01AG041122)
- National Cancer Institute (CA-96985, R01CA096985)
- 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
- progeroid mice, p21, p53, p19ARF, cellular senescence, aging, p16INK4a, skeletal muscle, adipose tissue, cataract, lens epithelial cells, progenitor cells
- MeSH terms
- Adipose Tissue, Alleles, Animals, Cataract, Cell Line, Genotype, Lens, Crystalline, Longevity, Mosaicism, Stem Cells, Tumor Suppressor Protein p53, Cellular Senescence, Protein Serine-Threonine Kinases, Muscle, Skeletal, Cell Cycle Proteins, Chromosome Disorders, Cyclin-Dependent Kinase Inhibitor p21, Cyclin-Dependent Kinase Inhibitor p19, Mice
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