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The right time for senescence
Open accessAbstract
Cellular senescence is a highly complex and programmed cellular state with diverse and, at times, conflicting physiological and pathological roles across the lifespan of an organism. Initially considered a cell culture artifact, senescence evolved from an age-related circumstance to an intricate cellular defense mechanism in response to stress, implicated in a wide spectrum of biological processes like tissue remodelling, injury and cancer. The development of new tools to study senescence in vivo paved the way to uncover its functional roles in various frameworks, which are sometimes hard to reconcile. Here, we review the functional impact of senescent cells on different organismal contexts. We provide updated insights on the role of senescent cells in tissue repair and regeneration, in which they essentially modulate the levels of fibrosis and inflammation, discussing how "time" seems to be the key maestro of their effects. Finally, we overview the current clinical research landscape to target senescent cells and contemplate its repercussions on this fast-evolving field.
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“Conversely, the progressive accumulation of senescent cells (facilitated by defective immunosurveillance) contributes to the phenomena of tissue fibrosis and lowgrade inflammation that define the aging process and exacerbate the risk of neoplastic transformation.176”
From Meta-hallmarks of aging and cancer (2023) · cites this paper as [176]
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Takahashi, K., & Yamanaka, S. (2006) · Cell · doi:10.1016/j.cell.2006.07.024 · Cited by 26,673
Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors
Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., & Yamanaka, S. (2007) · Cell · doi:10.1016/j.cell.2007.11.019 · Cited by 20,221
The serial cultivation of human diploid cell strains
Hayflick, L., & Moorhead, P. S. (1961) · Experimental Cell Research · doi:10.1016/0014-4827(61)90192-6 · Cited by 8,508
A biomarker that identifies senescent human cells in culture and in aging skin in vivo.
Dimri, G. P., Lee, X., Basile, G., Acosta, M., Scott, G., Roskelley, C., Medrano, E. E., Linskens, M., Rubelj, I., & Pereira-Smith, O. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.20.9363 · Cited by 7,477
The limited in vitro lifetime of human diploid cell strains
Hayflick, L. (1965) · Experimental Cell Research · doi:10.1016/0014-4827(65)90211-9 · Cited by 5,876
Telomeres shorten during ageing of human fibroblasts
Harley, C. B., Futcher, A. B., & Greider, C. W. (1990) · Nature · doi:10.1038/345458a0 · Cited by 5,750
Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a
Serrano, M., Lin, A. W., McCurrach, M. E., Beach, D., & Lowe, S. W. (1997) · Cell · doi:10.1016/s0092-8674(00)81902-9 · Cited by 5,218 · cited 2×
“The first experimental evidence of OIS came from the overexpression of oncogenic Ras in human fibroblasts, resulting in upregulation of p53, p16, pRB, and permanent cell cycle arrest (Serrano et al., 1997).”
BackgroundThe senescence-associated secretory phenotype: the dark side of tumor suppression
Coppé, J.-P., Desprez, P.-Y., Krtolica, A., & Campisi, J. (2010) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-121808-102144 · Cited by 5,206
Chronic inflammation in the etiology of disease across the life span
Furman, D., Campisi, J., Verdin, E., Carrera-Bastos, P., Targ, S., Franceschi, C., Ferrucci, L., Gilroy, D. W., Fasano, A., Miller, G. W., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0675-0 · Cited by 4,915
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 1×
“Remarkably, the use of progeroid mouse models has provided evidence that ablation of p16 cells improves many of these disease symptoms, reinforcing a detrimental role of SCs in aged tissues (Baker et al., 2011; Rhinn et al., 2019).”
BackgroundCellular Senescence: Defining a Path Forward
Gorgoulis, V., Adams, P. D., Alimonti, A., Bennett, D. C., Bischof, O., Bishop, C., Campisi, J., Collado, M., Evangelou, K., Ferbeyre, G., et al. (2019) · Cell · doi:10.1016/j.cell.2019.10.005 · Cited by 3,225 · cited 2×
“This multi- marker workflow includes: (1) screening for senescence with SA-β-gal and/or lipofuscin accumulation; (2) co- staining with markers frequently present (p16INK4a, p21CIP1) or absent (proliferation markers, Lamin B1) in SCs; and (3) identification of factors predicted to be altered in specific senescence cont…”
MethodAging, Cellular Senescence, and Cancer
Campisi, J. (2013) · Annual Review of Physiology · doi:10.1146/annurev-physiol-030212-183653 · Cited by 2,954 · cited 2×
“Aging entails a progressive loss of tissue functions that eventually leads to several chronic and agerelated diseases (Campisi, 2013).”
BackgroundNaturally 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 2,876
Cellular senescence: from physiology to pathology
Muñoz-Espín, D., & Serrano, M. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3823 · Cited by 2,818
The role of senescent cells in ageing
van Deursen, J. M. (2014) · Nature · doi:10.1038/nature13193 · Cited by 2,623
The Achilles' heel of senescent cells: from transcriptome to senolytic drugs
Zhu, Y., Tchkonia, T., Pirtskhalava, T., Gower, A. C., Ding, H., Giorgadze, N., Palmer, A. K., Ikeno, Y., Hubbard, G. B., Lenburg, M., et al. (2015) · Aging Cell · doi:10.1111/acel.12344 · Cited by 2,584
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 2,379 · cited 4×
“Therefore, paracrine senescence has been shown to mediate the deleterious effects of SCs on tissue homeostasis, namely in promoting tumourigenesis and agingrelated organ dysfunction, as well as in impairing regeneration (Campisi, 2005; FerreiraGonzalez et al., 2018; Gonzalez- Meljem et al., 2018).”
BackgroundInfluentialA complex secretory program orchestrated by the inflammasome controls paracrine senescence
Acosta, J. C., Banito, A., Wuestefeld, T., Georgilis, A., Janich, P., Morton, J. P., Athineos, D., Kang, T.-W., Lasitschka, F., Andrulis, M., et al. (2013) · Nature Cell Biology · doi:10.1038/ncb2784 · Cited by 2,278 · cited 2×
“Importantly, some SASP factors of tumour cells, such as TGF-β, VEGF, CCL2, and CCL20, also induce senescence in normal cells (Acosta et al., 2013).”
BackgroundOncogene-Induced Senescence Relayed by an Interleukin-Dependent Inflammatory Network
Kuilman, T., Michaloglou, C., Vredeveld, L. C. W., Douma, S., van Doorn, R., Desmet, C. J., Aarden, L. A., Mooi, W. J., & Peeper, D. S. (2008) · Cell · doi:10.1016/j.cell.2008.03.039 · Cited by 2,086 · cited 1×
“On the other hand, inhibition of IL- 1α and IL- 6 promotes OIS evasion (Di Mitri and Alimonti, 2016; Kuilman et al., 2008).”
BackgroundFour faces of cellular senescence
Rodier, F., & Campisi, J. (2011) · Journal of Cell Biology · doi:10.1083/jcb.201009094 · Cited by 2,070 · cited 3×
“Secretion of IL6 and IL- 8 has been shown to promote both tumourigenesis and tumour suppression in different contexts (Rodier and Campisi, 2011).”
BackgroundAn Essential Role for Senescent Cells in Optimal Wound Healing through Secretion of PDGF-AA
Demaria, M., Ohtani, N., Youssef, S. A., Rodier, F., Toussaint, W., Mitchell, J. R., Laberge, R.-M., Vijg, J., Van Steeg, H., Dollé, M. E. T., et al. (2014) · Developmental Cell · doi:10.1016/j.devcel.2014.11.012 · Cited by 2,045
Senescence of Activated Stellate Cells Limits Liver Fibrosis
Krizhanovsky, V., Yon, M., Dickins, R. A., Hearn, S., Simon, J., Miething, C., Yee, H., Zender, L., & Lowe, S. W. (2008) · Cell · doi:10.1016/j.cell.2008.09.015 · Cited by 2,027
Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis
Chen, Z., Trotman, L. C., Shaffer, D., Lin, H.-K., Dotan, Z. A., Niki, M., Koutcher, J. A., Scher, H. I., Ludwig, T., Gerald, W., et al. (2005) · Nature · doi:10.1038/nature03918 · Cited by 1,993
Krtolica, A., Parrinello, S., Lockett, S., Desprez, P.-Y., & Campisi, J. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.211053698 · Cited by 1,730
Cellular senescence mediates fibrotic pulmonary disease
Schafer, M. J., White, T. A., Iijima, K., Haak, A. J., Ligresti, G., Atkinson, E. J., Oberg, A. L., Birch, J., Salmonowicz, H., Zhu, Y., et al. (2017) · Nature Communications · doi:10.1038/ncomms14532 · Cited by 1,613 · cited 1×
“Similarly, in a mouse model of idiopathic pulmonary fibrosis (IPF), a chronic lung disease characterized by decreased lung function due to persistent scarring, senescent epithelial cells and fibroblasts accumulate continuously over time, inducing myofibroblast differentiation and exacerbating the fibrotic response (Sc…”
BackgroundSenescence-associated β-galactosidase is lysosomal β-galactosidase.
Lee, B. Y., Han, J. A., Im, J. S., Morrone, A., Johung, K., Goodwin, E. C., Kleijer, W. J., DiMaio, D., & Hwang, E. S. (2006) · Aging Cell · doi:10.1111/j.1474-9726.2006.00199.x · Cited by 1,444
Programmed cell senescence during mammalian embryonic development
Muñoz-Espín, D., Cañamero, M., Maraver, A., Gómez-López, G., Contreras, J., Murillo-Cuesta, S., Rodríguez-Baeza, A., Varela-Nieto, I., Ruberte, J., Collado, M., et al. (2013) · Cell · doi:10.1016/j.cell.2013.10.019 · Cited by 1,428
A proteomic atlas of senescence-associated secretomes for aging biomarker development
Basisty, N., Kale, A., Jeon, O. H., Kuehnemann, C., Payne, T., Rao, C., Holtz, A., Shah, S., Sharma, V., Ferrucci, L., et al. (2020) · PLOS Biology · doi:10.1371/journal.pbio.3000599 · Cited by 1,348
Suppression of induced pluripotent stem cell generation by the p53–p21 pathway
Hong, H., Takahashi, K., Ichisaka, T., Aoi, T., Kanagawa, O., Nakagawa, M., Okita, K., & Yamanaka, S. (2009) · Nature · doi:10.1038/nature08235 · Cited by 1,301
Cellular Senescence: Aging, Cancer, and Injury
Calcinotto, A., Kohli, J., Zagato, E., Pellegrini, L., Demaria, M., & Alimonti, A. (2019) · Physiological Reviews · doi:10.1152/physrev.00020.2018 · Cited by 1,270
Differential Roles of Macrophages in Diverse Phases of Skin Repair
Lucas, T., Waisman, A., Ranjan, R., Roes, J., Krieg, T., Müller, W., Roers, A., & Eming, S. A. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0903356 · Cited by 1,205 · cited 1×
“Recruited immune cells, namely macrophages and NK cells, can also execute proregenerative functions (Godwin et al., 2013; Lucas et al., 2010; Rajagopalan and Long, 2012).”
BackgroundSenescence is a developmental mechanism that contributes to embryonic growth and patterning
Storer, M., Mas, A., Robert-Moreno, A., Pecoraro, M., Ortells, M. C., Di Giacomo, V., Yosef, R., Pilpel, N., Krizhanovsky, V., Sharpe, J., et al. (2013) · Cell · doi:10.1016/j.cell.2013.10.041 · Cited by 1,186
Senescence-associated reprogramming promotes cancer stemness
Milanovic, M., Fan, D. N. Y., Belenki, D., Däbritz, J. H. M., Zhao, Z., Yu, Y., Dörr, J. R., Dimitrova, L., Lenze, D., Monteiro Barbosa, I. A., et al. (2018) · Nature · doi:10.1038/nature25167 · Cited by 1,131
Senescence in tumours: evidence from mice and humans
Collado, M., & Serrano, M. (2010) · Nature Reviews Cancer · doi:10.1038/nrc2772 · Cited by 1,124 · cited 1×
“Cancer Cellular senescence is a powerful barrier to tumourigenesis (Collado and Serrano, 2010).”
BackgroundStem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a
Janzen, V., Forkert, R., Fleming, H. E., Saito, Y., Waring, M. T., Dombkowski, D. M., Cheng, T., DePinho, R. A., Sharpless, N. E., & Scadden, D. T. (2006) · Nature · doi:10.1038/nature05159 · Cited by 1,106
Forging a signature of in vivo senescence
Sharpless, N. E., & Sherr, C. J. (2015) · Nature Reviews Cancer · doi:10.1038/nrc3960 · Cited by 1,104
Senolytic CAR T cells reverse senescence-associated pathologies
Amor, C., Feucht, J., Leibold, J., Ho, Y.-J., Zhu, C., Alonso-Curbelo, D., Mansilla-Soto, J., Boyer, J. A., Li, X., Giavridis, T., et al. (2020) · Nature · doi:10.1038/s41586-020-2403-9 · Cited by 1,098
A Senescence Program Controlled by p53 and p16INK4a Contributes to the Outcome of Cancer Therapy
Schmitt, C. A., Fridman, J. S., Yang, M., Lee, S., Baranov, E., Hoffman, R. M., & Lowe, S. W. (2002) · Cell · doi:10.1016/s0092-8674(02)00734-1 · Cited by 1,050
Geriatric 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
Jun, J.-I., & Lau, L. F. (2010) · Nature Cell Biology · doi:10.1038/ncb2070 · Cited by 998
The DNA damage response induces inflammation and senescence by inhibiting autophagy of GATA4.
Kang, C., Xu, Q., Martin, T. D., Li, M. Z., Demaria, M., Aron, L., Lu, T., Yankner, B. A., Campisi, J., & Elledge, S. J. (2015) · Science · doi:10.1126/science.aaa5612 · Cited by 982
Unmasking Transcriptional Heterogeneity in Senescent Cells
Hernandez-Segura, A., de Jong, T. V., Melov, S., Guryev, V., Campisi, J., & Demaria, M. (2017) · Current Biology · doi:10.1016/j.cub.2017.07.033 · Cited by 972
The Ink4/Arf locus is a barrier for iPS cell reprogramming
Li, H., Collado, M., Villasante, A., Strati, K., Ortega, S., Cañamero, M., Blasco, M. A., & Serrano, M. (2009) · Nature · doi:10.1038/nature08290 · Cited by 968
Wajapeyee, N., Serra, R. W., Zhu, X., Mahalingam, M., & Green, M. R. (2008) · Cell · doi:10.1016/j.cell.2007.12.032 · Cited by 903
Macrophages are required for adult salamander limb regeneration
Godwin, J. W., Pinto, A. R., & Rosenthal, N. A. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1300290110 · Cited by 829
Therapy-induced senescence in cancer.
Ewald, J. A., Desotelle, J. A., Wilding, G., & Jarrard, D. F. (2010) · JNCI: Journal of the National Cancer Institute · doi:10.1093/jnci/djq364 · Cited by 824
A senescent cell bystander effect: senescence‐induced senescence
Nelson, G., Wordsworth, J., Wang, C., Jurk, D., Lawless, C., Martin‐Ruiz, C., & von Zglinicki, T. (2012) · Aging Cell · doi:10.1111/j.1474-9726.2012.00795.x · Cited by 755
T-helper-1-cell cytokines drive cancer into senescence
Braumüller, H., Wieder, T., Brenner, E., Aßmann, S., Hahn, M., Alkhaled, M., Schilbach, K., Essmann, F., Kneilling, M., Griessinger, C., et al. (2013) · Nature · doi:10.1038/nature11824 · Cited by 720
Oxidative DNA damage and senescence of human diploid fibroblast cells.
Chen, Q., Fischer, A., Reagan, J. D., Yan, L. J., & Ames, B. N. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.10.4337 · Cited by 720
DNA damage response and cellular senescence in tissues of aging mice
Wang, C., Jurk, D., Maddick, M., Nelson, G., Martin‐Ruiz, C., & Von Zglinicki, T. (2009) · Aging Cell · doi:10.1111/j.1474-9726.2009.00481.x · Cited by 696
Rejuvenation of the muscle stem cell population restores strength to injured aged muscles
Cosgrove, B. D., Gilbert, P. M., Porpiglia, E., Mourkioti, F., Lee, S. P., Corbel, S. Y., Llewellyn, M. E., Delp, S. L., & Blau, H. M. (2014) · Nature Medicine · doi:10.1038/nm.3464 · Cited by 677
Opposing effects of Ets and Id proteins on p16INK4a expression during cellular senescence
Ohtani, N., Zebedee, Z., Huot, T. J. G., Stinson, J. A., Sugimoto, M., Ohashi, Y., Sharrocks, A. D., Peters, G., & Hara, E. (2001) · Nature · doi:10.1038/35059131 · Cited by 654
The senescence-associated secretory phenotype induces cellular plasticity and tissue regeneration.
Ritschka, B., Storer, M., Mas, A., Heinzmann, F., Ortells, M. C., Morton, J. P., Sansom, O. J., Zender, L., & Keyes, W. M. (2017) · Genes & Development · doi:10.1101/gad.290635.116 · Cited by 650
Senescence impairs successful reprogramming to pluripotent stem cells
Banito, A., Rashid, S. T., Acosta, J. C., Li, S., Pereira, C. F., Geti, I., Pinho, S., Silva, J. C., Azuara, V., Walsh, M., et al. (2009) · Genes & Development · doi:10.1101/gad.1811609 · Cited by 642
Mitochondrial dynamics in adaptive and maladaptive cellular stress responses
Eisner, V., Picard, M., & Hajnóczky, G. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0133-0 · Cited by 622
Secretion of vascular endothelial growth factor by primary human fibroblasts at senescence
Coppé, J.-P., Kauser, K., Campisi, J., & Beauséjour, C. M. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m603307200 · Cited by 604
Jurk, D., Wang, C., Miwa, S., Maddick, M., Korolchuk, V., Tsolou, A., Gonos, E. S., Thrasivoulou, C., Jill Saffrey, M., Cameron, K., et al. (2012) · Aging Cell · doi:10.1111/j.1474-9726.2012.00870.x · Cited by 598
Tissue 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
Accumulation of senescent cells in Mitotic tissue of aging primates
Jeyapalan, J. C., Ferreira, M., Sedivy, J. M., & Herbig, U. (2007) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2006.11.008 · Cited by 571
Senescent cells evade immune clearance via HLA-E-mediated NK and CD8+ T cell inhibition
Pereira, B. I., Devine, O. P., Vukmanovic-Stejic, M., Chambers, E. S., Subramanian, P., Patel, N., Virasami, A., Sebire, N. J., Kinsler, V., Valdovinos, A., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-10335-5 · Cited by 556
Rodier, F., Muñoz, D. P., Teachenor, R., Chu, V., Le, O., Bhaumik, D., Coppé, J.-P., Campeau, E., Beauséjour, C. M., Kim, S.-H., et al. (2011) · Journal of Cell Science · doi:10.1242/jcs.071340 · Cited by 535
Defined p16High Senescent Cell Types Are Indispensable for Mouse Healthspan
Grosse, L., Wagner, N., Emelyanov, A., Molina, C., Lacas-Gervais, S., Wagner, K.-D., & Bulavin, D. V. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.05.002 · Cited by 460
Toso, A., Revandkar, A., Di Mitri, D., Guccini, I., Proietti, M., Sarti, M., Pinton, S., Zhang, J., Kalathur, M., Civenni, G., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.08.044 · Cited by 418 · cited 1×
“with antagonists of CXCR2, a receptor for several SASP cytokines) may be used to enhance the efficacy of pro- senescence therapies and promote senescence immune surveillance (Calcinotto et al., 2019; Toso et al., 2014).”
Hall, B. M., Balan, V., Gleiberman, A. S., Strom, E., Krasnov, P., Virtuoso, L. P., Rydkina, E., Vujcic, S., Balan, K., Gitlin, I. I., et al. (2017) · Aging · doi:10.18632/aging.101268 · Cited by 407
Tumour-infiltrating Gr-1+ myeloid cells antagonize senescence in cancer
Di Mitri, D., Toso, A., Chen, J. J., Sarti, M., Pinton, S., Jost, T. R., D’Antuono, R., Montani, E., Garcia-Escudero, R., Guccini, I., et al. (2014) · Nature · doi:10.1038/nature13638 · Cited by 388
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
Interplay between oncogene-induced DNA damage response and heterochromatin in senescence and cancer
Di Micco, R., Sulli, G., Dobreva, M., Liontos, M., Botrugno, O. A., Gargiulo, G., dal Zuffo, R., Matti, V., d'Ario, G., Montani, E., et al. (2011) · Nature Cell Biology · doi:10.1038/ncb2170 · Cited by 382
Aged-senescent cells contribute to impaired heart regeneration
Lewis‐McDougall, F. C., Ruchaya, P. J., Domenjo‐Vila, E., Shin Teoh, T., Prata, L., Cottle, B. J., Clark, J. E., Punjabi, P. P., Awad, W., Torella, D., et al. (2019) · Aging Cell · doi:10.1111/acel.12931 · Cited by 317
Injury-Induced Senescence Enables In Vivo Reprogramming in Skeletal Muscle
Chiche, A., Le Roux, I., von Joest, M., Sakai, H., Aguín, S. B., Cazin, C., Salam, R., Fiette, L., Alegria, O., Flamant, P., et al. (2017) · Cell Stem Cell · doi:10.1016/j.stem.2016.11.020 · Cited by 295
Targeting senescent cells in translational medicine
Paez‐Ribes, M., González‐Gualda, E., Doherty, G. J., & Muñoz‐Espín, D. (2019) · EMBO Molecular Medicine · doi:10.15252/emmm.201810234 · Cited by 293
Neutrophil extracellular traps target senescent vasculature for tissue remodeling in retinopathy
Binet, F., Cagnone, G., Crespo-Garcia, S., Hata, M., Neault, M., Dejda, A., Wilson, A. M., Buscarlet, M., Mawambo, G. T., Howard, J. P., et al. (2020) · Science · doi:10.1126/science.aay5356 · Cited by 283
Cellular senescence and the aging brain
Chinta, S. J., Woods, G., Rane, A., Demaria, M., Campisi, J., & Andersen, J. K. (2015) · Experimental Gerontology · doi:10.1016/j.exger.2014.09.018 · Cited by 282
Cellular senescence in development, regeneration and disease
Rhinn, M., Ritschka, B., & Keyes, W. M. (2019) · Development · doi:10.1242/dev.151837 · Cited by 279
The promises and perils of p53
Krizhanovsky, V., & Lowe, S. W. (2009) · Nature · doi:10.1038/4601085a · Cited by 274
Identification of senescent cell surface targetable protein DPP4
Kim, K. M., Noh, J. H., Bodogai, M., Martindale, J. L., Yang, X., Indig, F. E., Basu, S. K., Ohnuma, K., Morimoto, C., Johnson, P. F., et al. (2017) · Genes & Development · doi:10.1101/gad.302570.117 · Cited by 270
Cell fusion induced by ERVWE1 or measles virus causes cellular senescence
Chuprin, A., Gal, H., Biron-Shental, T., Biran, A., Amiel, A., Rozenblatt, S., & Krizhanovsky, V. (2013) · Genes & Development · doi:10.1101/gad.227512.113 · Cited by 262
Tumor cell escape from therapy-induced senescence as a model of disease recurrence after dormancy.
Saleh, T., Tyutyunyk-Massey, L., & Gewirtz, D. A. (2019) · Cancer Research · doi:10.1158/0008-5472.can-18-3437 · Cited by 259
Essential role for premature senescence of myofibroblasts in myocardial fibrosis
Meyer, K., Hodwin, B., Ramanujam, D., Engelhardt, S., & Sarikas, A. (2016) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2016.02.047 · Cited by 247
AP-1 imprints a reversible transcriptional programme of senescent cells.
Martínez-Zamudio, R. I., Roux, P.-F., de Freitas, J. A. N. L. F., Robinson, L., Doré, G., Sun, B., Belenki, D., Milanovic, M., Herbig, U., Schmitt, C. A., et al. (2020) · Nature Cell Biology · doi:10.1038/s41556-020-0529-5 · Cited by 236
Senescent Cardiac Fibroblast Is Critical for Cardiac Fibrosis after Myocardial Infarction
Zhu, F., Li, Y., Zhang, J., Piao, C., Liu, T., Li, H.-H., & Du, J. (2013) · PLoS ONE · doi:10.1371/journal.pone.0074535 · Cited by 201
Saito, Y., Chikenji, T. S., Matsumura, T., Nakano, M., & Fujimiya, M. (2020) · Nature Communications · doi:10.1038/s41467-020-14734-x · Cited by 196
Frailty in childhood cancer survivors
Ness, K. K., Armstrong, G. T., Kundu, M., Wilson, C. L., Tchkonia, T., & Kirkland, J. L. (2015) · Cancer · doi:10.1002/cncr.29211 · Cited by 188
Tumor Stroma-Derived TGF-β Limits Myc-Driven Lymphomagenesis via Suv39h1-Dependent Senescence
Reimann, M., Lee, S., Loddenkemper, C., Dörr, J. R., Tabor, V., Aichele, P., Stein, H., Dörken, B., Jenuwein, T., & Schmitt, C. A. (2010) · Cancer Cell · doi:10.1016/j.ccr.2009.12.043 · Cited by 184
Paracrine roles of cellular senescence in promoting tumourigenesis
Gonzalez-Meljem, J. M., Apps, J. R., Fraser, H. C., & Martinez-Barbera, J. P. (2018) · British Journal of Cancer · doi:10.1038/s41416-018-0066-1 · Cited by 183
Cellular Senescence Limits Regenerative Capacity and Allograft Survival
Braun, H., Schmidt, B. M. W., Raiss, M., Baisantry, A., Mircea-Constantin, D., Wang, S., Groß, M.-L., Serrano, M., Schmitt, R., & Melk, A. (2012) · Journal of the American Society of Nephrology · doi:10.1681/asn.2011100967 · Cited by 180
Clearance of senescent cells during cardiac ischemia–reperfusion injury improves recovery
Dookun, E., Walaszczyk, A., Redgrave, R., Palmowski, P., Tual‐Chalot, S., Suwana, A., Chapman, J., Jirkovsky, E., Donastorg Sosa, L., Gill, E., et al. (2020) · Aging Cell · doi:10.1111/acel.13249 · Cited by 173
Le, 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
Cellular senescence induced by CD158d reprograms natural killer cells to promote vascular remodeling
Rajagopalan, S., & Long, E. O. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1208248109 · Cited by 168
Paracrine cellular senescence exacerbates biliary injury and impairs regeneration
Ferreira-Gonzalez, S., Lu, W.-Y., Raven, A., Dwyer, B., Man, T. Y., O’Duibhir, E., Lewis, P. J. S., Campana, L., Kendall, T. J., Bird, T. G., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03299-5 · Cited by 161
Cell Senescence in the Aging Kidney
Yang, H., & Fogo, A. B. (2010) · Journal of the American Society of Nephrology · doi:10.1681/asn.2010020205 · Cited by 158
Oncogene-induced senescence results in marked metabolic and bioenergetic alterations
Quijano, C., Cao, L., Fergusson, M. M., Romero, H., Liu, J., Gutkind, S., Rovira, I. I., Mohney, R. P., Karoly, E. D., & Finkel, T. (2012) · Cell Cycle · doi:10.4161/cc.19800 · Cited by 155
Cellular senescence impact on immune cell fate and function
Vicente, R., Mausset-Bonnefont, A.-L., Jorgensen, C., Louis-Plence, P., & Brondello, J.-M. (2016) · Aging Cell · doi:10.1111/acel.12455 · Cited by 151
Frescas, D., Roux, C. M., Aygun-Sunar, S., Gleiberman, A. S., Krasnov, P., Kurnasov, O. V., Strom, E., Virtuoso, L. P., Wrobel, M., Osterman, A. L., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1614661114 · Cited by 140
Kang, C. (2019) · Europe PMC (PubMed Central) · doi:10.14348/molcells.2019.0298 · Cited by 129
Cortical neurons develop a senescence-like phenotype promoted by dysfunctional autophagy
Moreno-Blas, D., Gorostieta-Salas, E., Pommer-Alba, A., Muciño-Hernández, G., Gerónimo-Olvera, C., Maciel-Barón, L. A., Konigsberg, M., Massieu, L., & Castro-Obregón, S. (2019) · Aging · doi:10.18632/aging.102181 · Cited by 128
Cell senescence contributes to tissue regeneration in zebrafish
Da Silva‐Álvarez, S., Guerra‐Varela, J., Sobrido‐Cameán, D., Quelle, A., Barreiro‐Iglesias, A., Sánchez, L., & Collado, M. (2020) · Aging Cell · doi:10.1111/acel.13052 · Cited by 126
Conserved and novel functions of programmed cellular senescence during vertebrate development
Davaapil, H., Brockes, J. P., & Yun, M. H. (2016) · Development · doi:10.1242/dev.138222 · Cited by 124
Tanaka, H. V., Ng, N. C. Y., Yu, Z. Y., Casco‐Robles, M. M., Maruo, F., Tsonis, P. A., & Chiba, C. (2016) · Nature Communications · doi:10.1038/ncomms11069 · Cited by 105
Ritschka, B., Knauer-Meyer, T., Gonçalves, D. S., Mas, A., Plassat, J.-L., Durik, M., Jacobs, H., Pedone, E., Di Vicino, U., Cosma, M. P., et al. (2020) · Genes & Development · doi:10.1101/gad.332643.119 · Cited by 105
Functional Aging and Gradual Senescence in Zebrafish
Kishi, S. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1297.097 · Cited by 103
Zhao, Y., Tyshkovskiy, A., Muñoz‐Espín, D., Tian, X., Serrano, M., de Magalhães, J. P., Nevo, E., Gladyshev, V. N., Seluanov, A., & Gorbunova, V. A. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1721160115 · Cited by 96
Non-Cell-Autonomous Regulation of Cellular Senescence in Cancer
Mitri, D. D., & Alimonti, A. (2015) · Trends in Cell Biology · doi:10.1016/j.tcb.2015.10.005 · Cited by 92
Kornicka, K., Szłapka‐Kosarzewska, J., Śmieszek, A., & Marycz, K. (2018) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.13914 · Cited by 92
Transient p53-Mediated Regenerative Senescence in the Injured Heart
Sarig, R., Rimmer, R., Bassat, E., Zhang, L., Umansky, K. B., Lendengolts, D., Perlmoter, G., Yaniv, K., & Tzahor, E. (2019) · Circulation · doi:10.1161/circulationaha.119.040125 · Cited by 87
Telomerase Is Essential for Zebrafish Heart Regeneration
Bednarek, D., González‐Rosa, J. M., Guzmán, G., Gutiérrez‐Gutiérrez, Ó., Aguado, T., Sánchez-Ferrer, C., Marques, I. J., Galardi‐Castilla, M., de Diego, I., Gómez, M. J., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.07.064 · Cited by 84
Xu, S., Wu, W., Huang, H., Huang, R., Xie, L., Su, A., Liu, S., Zheng, R., Yuan, Y., Zheng, H., et al. (2019) · Aging Cell · doi:10.1111/acel.12918 · Cited by 79
Targeting senescent cells improves functional recovery after spinal cord injury
Paramos-de-Carvalho, D., Martins, I., Cristóvão, A. M., Dias, A. F., Neves-Silva, D., Pereira, T., Chapela, D., Farinho, A., Jacinto, A., & Saúde, L. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109334 · Cited by 74
Self-citationCD9 induces cellular senescence and aggravates atherosclerotic plaque formation
Cho, J. H., Kim, E.-C., Son, Y., Lee, D.-W., Park, Y. S., Choi, J. H., Cho, K., Kwon, K., & Kim, J.-R. (2020) · Cell Death and Differentiation · doi:10.1038/s41418-020-0537-9 · Cited by 73
An, S., Cho, S., Kang, J., Lee, S., Kim, H.-S., Min, D., Son, E.-D., & Cho, K. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1920338117 · Cited by 62
Kennedy, A. L., McBryan, T., Enders, G. H., Johnson, F. B., Zhang, R., & Adams, P. D. (2010) · Cell Division · doi:10.1186/1747-1028-5-16 · Cited by 61
TGFβ2-induced senescence during early inner ear development
Gibaja, A., Aburto, M. R., Pulido, S., Collado, M., Hurlé, J. M., Varela‐Nieto, I., & Magariños, M. (2019) · Scientific Reports · doi:10.1038/s41598-019-42040-0 · Cited by 60
Telomere shortening produces an inflammatory environment that increases tumor incidence in zebrafish
Lex, K., Maia-Gil, M., Lopes-Bastos, B., Figueira, M., Marzullo, M., Giannetti, K., Carvalho, T., & Ferreira, M. G. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1920049117 · Cited by 60
HMGB1 modulates the balance between senescence and apoptosis in response to genotoxic stress
Lee, J., Park, I. H., Rhee, W. J., Kim, H. S., & Shin, J. (2019) · The FASEB Journal · doi:10.1096/fj.201900288r · Cited by 57
Senescence gives insights into the morphogenetic evolution of anamniotes
Villiard, É., Denis, J.-F., Hashemi, F. S., Igelmann, S., Ferbeyre, G., & Roy, S. (2017) · Biology Open · doi:10.1242/bio.025809 · Cited by 52
Marcoux, S., Lê, O., Langlois-Pelletier, C., Laverdière, C., Hatami, A., Robaey, P., & Beausejour, C. M. (2013) · Radiation Oncology · doi:10.1186/1748-717x-8-252 · Cited by 49
The quail mesonephros: a new model for renal senescence?
Nacher, V., Carretero, A., Navarro, M., Armengol, C., Llombart, C., Rodríguez, A., Herrero-Fresneda, I., Ayuso, E., & Ruberte, J. (2006) · Journal of Vascular Research · doi:10.1159/000096076 · Cited by 47
Maï, M. E., Marzullo, M., de Castro, I. P., & Ferreira, M. G. (2020) · eLife · doi:10.7554/elife.54935 · Cited by 47
Cellular senescence in tissue repair: every cloud has a silver lining
Yun, M. H. (2018) · The International Journal of Developmental Biology · doi:10.1387/ijdb.180081my · Cited by 44
Huang, T., & Rivera‐Pérez, J. A. (2014) · genesis · doi:10.1002/dvg.22761 · Cited by 38
Developmentally-programmed cellular senescence is conserved and widespread in zebrafish
Silva‐Álvarez, S. D., Guerra‐Varela, J., Sobrido‐Cameán, D., Quelle‐Regaldie, A., Barreiro‐Iglesias, A., Sanchez, L. E., & Collado, M. (2020) · Aging · doi:10.18632/aging.103968 · Cited by 35
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Walton, C. C., & Andersen, J. K. (2019) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2019.01.012 · Cited by 28
Wang, S., Liu, Y., Liu, Y., Li, C., Wan, Q., Liu, Y., Su, Y., Cheng, Y., Liu, C., Wang, X., et al. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.588050 · Cited by 20
Graham, Z., Goldberger, A., Azulai, D., Conover, C. F., Ye, F., Bauman, W. A., Cardozo, C. P., & Yarrow, J. F. (2020) · Physiological Reports · doi:10.14814/phy2.14357 · Cited by 13
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Cellular senescence: a key therapeutic target in aging and diseases
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Metadata
- Authors
- Paramos-de-Carvalho, D., Jacinto, A., & Saúde, L.
- Affiliations
- University of Lisbon (PT)
- CEDOC, NOVA Medical School, Faculdade de Ciências Médicas da Universidade Nova de Lisboa
- Corresponding author
- Paramos-de-Carvalho, Diogo
- Saúde, Leonor
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2021-11-10
- Volume
- 10
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC8580479
- OpenAlex
- W3211748729
- Cited by
- 111
- References
- 123
- Citations by year
- 2026: 8 · 2025: 24 · 2024: 30 · 2023: 34 · 2022: 14
- FWCI
- 2.60
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Fundação para a Ciência e a Tecnologia (PD/BD/105770/2014, PTDC/MED-NEU/30428/2017, HR18-00187)
- "la Caixa" Banking Foundation (HR18-00187)
- Santa Casa da Misericórdia de Lisboa (MC36-2020 (Melo e Castro Award))
- 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 › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Keywords
- cellular senescence, senolytics, tissue repair, tissue regeneration, fibrosis, inflammation, aging, stress response, cancer
- MeSH terms
- Aging, Animals, Fibrosis, Humans, Inflammation, Regeneration, Cellular Senescence
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