Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype

Abbas, 2009, P21 in cancer: intricate networks and multiple activities., Nat. Rev. Cancer, 9, 400, 10.1038/nrc2657

Ablasser, 2013, CGAS produces a 2′-5′-linked cyclic dinucleotide second messenger that activates STING., Nature, 498, 380, 10.1038/nature12306

Ablasser, 2016, The role of cGAS in innate immunity and beyond., J. Mol. Med., 94, 1085, 10.1007/s00109-016-1423-2

Acosta, 2013, A complex secretory program orchestrated by the inflammasome controls paracrine senescence., Nat. Cell Biol., 15, 978, 10.1038/ncb2784

Acosta, 2008, Chemokine signaling via the CXCR2 receptor reinforces senescence., Cell, 133, 1006, 10.1016/j.cell.2008.03.038

Adams, 2007, Remodeling chromatin for senescence., Aging Cell, 6, 425, 10.1111/j.1474-9726.2007.00313.x

Adan, 2016, Cell proliferation and cytotoxicity assays., Curr. Pharm. Biotechnol., 17, 1213, 10.2174/1389201017666160808160513

Agger, 2009, The H3K27me3 demethylase JMJD3 contributes to the activation of the INK4A–ARF locus in response to oncogene- and stress-induced senescence., Genes Dev., 23, 1171, 10.1101/gad.510809.GENES

Aird, 2013, Detection of senescence-associated heterochromatin foci (SAHF)., Methods Mol. Biol., 965, 185, 10.1007/978-1-62703-239-1_12

Al Bitar, 2019, The role of the cyclin dependent kinase inhibitor p21cip1/waf1 in targeting cancer: Molecular mechanisms and novel therapeutics., Cancers (Basel), 11, 10.3390/cancers11101475

Alimonti, 2010, A novel type of cellular senescence that can be enhanced in mouse models and human tumor xenografts to suppress prostate tumorigenesis., J. Clin. Invest., 120, 681, 10.1172/JCI40535

Aliouat-Denis, 2005, p53-independent regulation of p21Waf1/Cip1 expression and senescence by Chk2., Mol. Cancer Res., 3, 627, 10.1158/1541-7786.MCR-05-0121

Allavena, 2008, The inflammatory micro-environment in tumor progression: the role of tumor-associated macrophages., Crit. Rev. Oncol. Hematol., 66, 1, 10.1016/j.critrevonc.2007.07.004

Ayrapetov, 2014, DNA double-strand breaks promote methylation of histone H3 on lysine 9 and transient formation of repressive chromatin., Proc. Natl. Acad. Sci. U.S.A., 111, 9169, 10.1073/pnas.1403565111

Baar, 2017, Targeted apoptosis of senescent cells restores tissue homeostasis in response to chemotoxicity and aging., Cell, 169, 132, 10.1016/j.cell.2017.02.031

Baker, 2016, Naturally occurring p16 Ink4a-positive cells shorten healthy lifespan., Nature, 530, 184, 10.1038/nature16932

Baker, 2011, Clearance of p16 Ink4a-positive senescent cells delays ageing-associated disorders., Nature, 479, 232, 10.1038/nature10600

Baker, 2019, MicroRNA-570 is a novel regulator of cellular senescence and inflammaging., FASEB J., 33, 1605, 10.1096/fj.201800965R

Banito, 2010, Induced pluripotent stem cells and senescence: Learning the biology to improve the technology., EMBO Rep., 11, 353, 10.1038/embor.2010.47

Barber, 2015, STING: infection, inflammation and cancer., Nat. Publ. Gr., 15, 760, 10.1038/nri3921

Barnes, 2019, Cellular senescence as a mechanism and target in chronic lung diseases., Am. J. Respir. Crit. Care Med., 200, 556, 10.1164/rccm.201810-1975TR

Barradas, 2009, Histone demethylase JMJD3 contributes to epigenetic control of INK4a/ARF by oncogenic RAS., Genes Dev., 23, 1177, 10.1101/gad.511109

Bartkova, 2006, Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints., Nature, 444, 633, 10.1038/nature05268

Baumann, 2016, Cellular senescence: senescence and reprogramming go hand-in-hand., Nat. Rev. Mol. Cell Biol., 18, 10.1038/nrm.2016.165

Beauséjour, 2003, Reversal of human cellular senescence: Roles of the p53 and p16 pathways., EMBO J., 22, 4212, 10.1093/emboj/cdg417

Benhamed, 2012, Senescence is an endogenous trigger for microRNA-directed transcriptional gene silencing in human cells., Nat. Cell Biol., 14, 266, 10.1038/ncb2443

Bent, 2016, A senescence secretory switch mediated by PI3K/AKT/mTOR activation controls chemoprotective endothelial secretory responses., Genes Dev., 30, 1811, 10.1101/gad.284851.116

Bhaskara, 2016, Examination of proteins bound to nascent DNA in mammalian cells using brdU-ChIP-slot-western technique., J. Vis. Exp., 2016, 10.3791/53647

Bhaumik, 2009, MicroRNAs miR-146a/b negatively modulate the senescence-associated inflammatory mediators IL-6 and IL-8., Aging (Albany NY), 1, 402, 10.18632/aging.100042

Biran, 2015, Senescent cells communicate via intercellular protein transfer., Genes Dev., 29, 791, 10.1101/gad.259341.115

Blagosklonny, 2012, Cell cycle arrest is not yet senescence, which is not just cell cycle arrest: terminology for TOR-driven aging., Aging (Albany NY), 4, 159, 10.18632/aging.100443

Blagosklonny, 2013, Aging is not programmed: genetic pseudo-program is a shadow of developmental growth., Cell Cycle, 12, 3736, 10.4161/cc.27188

Boisvert, 2018, The aging astrocyte transcriptome from multiple regions of the mouse brain., Cell Rep., 22, 269, 10.1016/j.celrep.2017.12.039

Boon, 2013, MicroRNA-34a regulates cardiac ageing and function., Nature, 495, 107, 10.1038/nature11919

Borgdorff, 2010, Multiple microRNAs rescue from Ras-induced senescence by inhibiting p21 Waf1/Cip1., Oncogene, 29, 2262, 10.1038/onc.2009.497

Boumendil, 2019, Nuclear pore density controls heterochromatin reorganization during senescence., Genes Dev., 33, 144, 10.1101/gad.321117.118

Bracken, 2007, The Polycomb group proteins bind throughout the INK4A-ARF locus and are disassociated in senescent cells., Genes Dev., 21, 525, 10.1101/gad.415507

Bracken, 2003, EZH2 is downstream of the pRB-E2F pathway, essential for proliferation and amplified in cancer., EMBO J., 22, 5323, 10.1093/emboj/cdg542

Burns, 2011, CPEB and two poly(A) polymerases control miR-122 stability and p53 mRNA translation., Nature, 473, 105, 10.1038/nature09908

Burton, 2014, Physiological and pathological consequences of cellular senescence., Cell. Mol. Life Sci., 71, 4373, 10.1007/s00018-014-1691-3

Calcinotto, 2019, Cellular senescence: aging, cancer, and injury., Physiol. Rev., 99, 1047, 10.1152/physrev.00020.2018

Campisi, 2003, Cancer and ageing: rival demons?, Nat. Rev. Cancer, 3, 339, 10.1038/nrc1073

Campisi, 2011, Cellular senescence: a link between cancer and age-related degenerative disease?, Semin. Cancer Biol., 21, 354, 10.1016/j.semcancer.2011.09.001

Campisi, 2007, Cellular senescence: when bad things happen to good cells., Nat. Rev. Mol. Cell Biol., 8, 729, 10.1038/nrm2233

Capell, 2016, Mll1 is essential for the senescenceassociated secretory phenotype., Genes Dev., 30, 321, 10.1101/gad.271882.115

Carnero, 2013, Markers of cellular senescence., Methods Mol. Biol., 965, 63, 10.1007/978-1-62703-239-1_4

Cavanagh, 2011, Thymidine analogues for tracking DNA synthesis., Molecules, 16, 7980, 10.3390/molecules16097980

Chan, 2019, Short-term gain, long-term pain: the senescence life cycle and cancer., Genes Dev., 33, 127, 10.1101/gad.320937.118

Chandra, 2016, Senescence associated heterochromatic foci: SAHF, The Functional Nucleus, 205, 10.1007/978-3-319-38882-3_9

Chandra, 2015, Global reorganization of the nuclear landscape in senescent cells., Cell Rep., 10, 471, 10.1016/j.celrep.2014.12.055

Chandra, 2012, Independence of repressive histone marks and chromatin compaction during senescent heterochromatic layer formation., Mol. Cell, 47, 203, 10.1016/j.molcel.2012.06.010

Chandrasekaran, 2017, Redox control of senescence and age-related disease., Redox Biol., 11, 91, 10.1016/j.redox.2016.11.005

Chau, 2003, Coordinated regulation of life and death by RB., Nat. Rev. Cancer, 3, 130, 10.1038/nrc993

Chehab, 1999, Phosphorylation of Ser-20 mediates stabilization of human p53 in response to DNA damage., Proc. Natl. Acad. Sci. U.S.A., 96, 13777, 10.1073/pnas.96.24.13777

Chen, 2018, Targeting SPINK1 in the damaged tumour microenvironment alleviates therapeutic resistance., Nat. Commun., 9, 10.1038/s41467-018-06860-4

Chen, 2015, MacroH2A1 and ATM play opposing roles in paracrine senescence and the senescence-associated secretory phenotype., Mol. Cell, 59, 719, 10.1016/j.molcel.2015.07.011

Chen, 1996, Cyclin-binding motifs are essential for the function of p21CIP1., Mol. Cell. Biol., 16, 4673, 10.1128/MCB.16.9.4673

Chen, 2016, Regulation and function of the cGAS-STING pathway of cytosolic DNA sensing., Nat. Immunol., 17, 1142, 10.1038/ni.3558

Cheng, 2017, Epigenetic regulation in cell senescence., J. Mol. Med., 95, 1257, 10.1007/s00109-017-1581-x

Cheng, 1999, The p21(Cip1) and p27(Kip1) CDK “inhibitors” are essential activators of cyclin D-dependent kinases in murine fibroblasts., EMBO J., 18, 1571, 10.1093/emboj/18.6.1571

Chien, 2011, Control of the senescence-associated secretory phenotype by NF-κB promotes senescence and enhances chemosensitivity., Genes Dev., 25, 2125, 10.1101/gad.17276711

Child, 2006, The intricacies of p21 phosphorylation: protein/protein interactions, subcellular localization and stability., Cell Cycle, 5, 1313, 10.4161/cc.5.12.2863

Childs, 2014, Senescence and apoptosis: dueling or complementary cell fates?, EMBO Rep., 15, 1139, 10.15252/embr.201439245

Childs, 2015, Cellular senescence in aging and age-related disease: from mechanisms to therapy., Nat. Med., 21, 1424, 10.1038/nm.4000

Childs, 2017, Senescent cells: an emerging target for diseases of ageing., Nat. Rev. Drug Discov., 16, 718, 10.1038/nrd.2017.116

Chung, 2009, Molecular inflammation: underpinnings of aging and age-related diseases., Ageing Res. Rev., 8, 18, 10.1016/j.arr.2008.07.002

Collado, 2007, Cellular senescence in cancer and aging., Cell, 130, 223, 10.1016/j.cell.2007.07.003

Contrepois, 2017, Histone variant H2A. J accumulates in senescent cells and promotes inflammatory gene expression., Nat. Commun., 8, 10.1038/ncomms14995

Coppé, , The senescence-associated secretory phenotype: the dark side of tumor suppression., Annu. Rev. Pathol. Mech. Dis., 5, 99, 10.1146/annurev-pathol-121808-102144

Coppé, 2006, Secretion of vascular endothelial growth factor by primary human fibroblasts at senescence., J. Biol. Chem., 281, 29568, 10.1074/jbc.M603307200

Coppé, , A human-like senescence-associated secretory phenotype is conserved in mouse cells dependent on physiological oxygen., PLoS One, 5, 10.1371/journal.pone.0009188

Coppé, 2008, Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor., PLoS Biol., 6, 2853, 10.1371/journal.pbio.0060301

Coppé, 2011, Tumor suppressor and aging biomarker p16 INK4a induces cellular senescence without the associated inflammatory secretory phenotype., J. Biol. Chem., 286, 36396, 10.1074/jbc.M111.257071

Crane, 2013, The use of bromodeoxyuridine incorporation assays to assess corneal stem cell proliferation., Methods Mol. Biol., 1014, 65, 10.1007/978-1-62703-432-6_4

Criscione, 2016, The chromatin landscape of cellular senescence., Trends Genet., 32, 751, 10.1016/j.tig.2016.09.005

Cruickshanks, 2013, Senescent cells harbour features of the cancer epigenome., Nat. Cell Biol., 15, 1495, 10.1038/ncb2879

Da Silva-Álvarez, 2019, The development of cell senescence., Exp. Gerontol., 128, 10.1016/j.exger.2019.110742

Dabrowska, 2018, Oxidative stress and inhibition of nitric oxide generation underlie methotrexate-induced senescence in human colon cancer cells., Mech. Ageing Dev., 170, 22, 10.1016/j.mad.2017.07.006

D’Adda Di Fagagna, 2003, A DNA damage checkpoint response in telomere-initiated senescence., Nature, 426, 194, 10.1038/nature02118

D’Adda Di Fagagna, 2008, Living on a break: cellular senescence as a DNA-damage response., Nat. Rev. Cancer, 8, 512, 10.1038/nrc2440

Davalos, 2010, Senescent cells as a source of inflammatory factors for tumor progression., Cancer Metastasis Rev., 29, 273, 10.1007/s10555-010-9220-9

Davalos, 2013, p53-dependent release of Alarmin HMGB1 is a central mediator of senescent phenotypes., J. Cell Biol., 201, 613, 10.1083/jcb.201206006

De Cecco, 2013, Genomes of replicatively senescent cells undergo global epigenetic changes leading to gene silencing and activation of transposable elements., Aging Cell, 12, 247, 10.1111/acel.12047

De Cecco, 2019, L1 drives IFN in senescent cells and promotes age-associated inflammation., Nature, 566, 73, 10.1038/s41586-018-0784-9

Debacq-Chainiaux, 2016, Stress-induced (Premature) senescence, Cellular Ageing and Replicative Senescence. Healthy Ageing and Longevity, 243, 10.1007/978-3-319-26239-0_13

Demaria, 2014, An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA., Dev. Cell, 31, 722, 10.1016/j.devcel.2014.11.012

Demaria, 2017, Cellular senescence promotes adverse effects of chemotherapy and cancer relapse., Cancer Discov., 7, 165, 10.1158/2159-8290.CD-16-0241

Demontis, 2010, FOXO/4E-BP signaling in Drosophila muscles regulates organism-wide proteostasis during aging., Cell, 143, 813, 10.1016/j.cell.2010.10.007

Deng, 2018, Deubiquitylation and stabilization of p21 by USP11 is critical for cell-cycle progression and DNA damage responses., Proc. Natl. Acad. Sci. U. S. A., 115, 4678, 10.1073/pnas.1714938115

Di Leonardo, 1994, DNA damage triggers a prolonged p53-dependent G1arrest and long-term induction of Cip1 in normal human fibroblasts., Genes Dev., 8, 2540, 10.1101/gad.8.21.2540

Di Martino, 2018, HSP90 inhibition alters the chemotherapy-driven rearrangement of the oncogenic secretome., Oncogene, 37, 1369, 10.1038/s41388-017-0044-8

Di Micco, 2006, Oncogene-induced senescence is a DNA damage response triggered by DNA hyper-replication., Nature, 444, 638, 10.1038/nature05327

Di Micco, 2011, Interplay between oncogene-induced DNA damage response and heterochromatin in senescence and cancer., Nat. Cell Biol., 13, 292, 10.1038/ncb2170

Di Mitri, 2014, Tumour-infiltrating Gr-1 + myeloid cells antagonize senescence in cancer., Nature, 515, 134, 10.1038/nature13638

Diner, 2013, The innate immune DNA Sensor cGAS produces a noncanonical cyclic dinucleotide that activates human STING., Cell Rep., 3, 1355, 10.1016/j.celrep.2013.05.009

Dörr, 2013, Synthetic lethal metabolic targeting of cellular senescence in cancer therapy., Nature, 501, 421, 10.1038/nature12437

Dou, 2017, Cytoplasmic chromatin triggers inflammation in senescence and cancer., Nature, 550, 402, 10.1038/nature24050

Dyson, 1998, The regulation of E2F by pRB-family proteins., Genes Dev., 12, 2245, 10.1101/gad.12.15.2245

Dyson, 2016, RB1: a prototype tumor suppressor and an enigma., Genes Dev., 30, 1492, 10.1101/gad.282145.116

Effenberger, 2014, Senescence-associated release of transmembrane proteins involves proteolytic processing by ADAM17 and microvesicle shedding., FASEB J., 28, 4847, 10.1096/fj.14-254565

Eggert, 2016, Distinct functions of senescence-associated immune responses in liver tumor surveillance and tumor progression., Cancer Cell, 30, 533, 10.1016/j.ccell.2016.09.003

Eijkelenboom, 2013, FOXOs: signalling integrators for homeostasis maintenance., Nat. Rev. Mol. Cell Biol., 14, 83, 10.1038/nrm3507

El-Deiry, 1993, WAF1, a potential mediator of ~53 tumor suppression., Cell, 75, 817, 10.1016/0092-8674(93)90500-P

Elzi, 2012, Plasminogen activator inhibitor 1 – Insulin-like growth factor binding protein 3 cascade regulates stress-induced senescence., Proc. Natl. Acad. Sci. U.S.A., 109, 12052, 10.1073/pnas.1120437109

Engeland, 2017, Cell cycle arrest through indirect transcriptional repression by p53: I have a DREAM., Cell Death Differ., 25, 114, 10.1038/cdd.2017.172

Evangelou, 2013, The DNA damage checkpoint precedes activation of ARF in response to escalating oncogenic stress during tumorigenesis., Cell Death Differ., 20, 1485, 10.1038/cdd.2013.76

Ewald, 2010, Therapy-induced senescence in cancer., J. Natl. Cancer Inst., 102, 1536, 10.1093/jnci/djq364

Faget, 2019, Unmasking senescence: context-dependent effects of SASP in cancer., Nat. Rev. Cancer, 19, 439, 10.1038/s41568-019-0156-2

Fay, 2007, The SynMuv genes of Caenorhabditis elegans in vulval development and beyond., Dev. Biol., 306, 1, 10.1016/j.ydbio.2007.03.016

Ferbeyre, 2000, PML is induced by oncogenic ras and promotes premature senescence., Genes Dev., 14, 2015, 10.1101/gad.14.16.2015

Fischer, , Integration of TP53, DREAM, MMB-FOXM1 and RB-E2F target gene analyses identifies cell cycle gene regulatory networks., Nucleic Acids Res., 44, 6070, 10.1093/nar/gkw523

Fischer, 2017, Cell cycle transcription control: DREAM/MuvB and RB-E2F complexes., Crit. Rev. Biochem. Mol. Biol., 52, 638, 10.1080/10409238.2017.1360836

Fischer, , The p53-p21-DREAM-CDE/CHR pathway regulates G2/M cell cycle genes., Nucleic Acids Res., 44, 164, 10.1093/nar/gkv927

Fischer, 2014, The transcription factor p53: Not a repressor, solely an activator., Cell Cycle, 13, 3037, 10.4161/15384101.2014.949083

Franceschi, 2014, Chronic inflammation (Inflammaging) and its potential contribution to age-associated diseases., Journals Gerontol., 69, S4, 10.1093/gerona/glu057

Franceschi, 2007, Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans., Mech. Ageing Dev., 128, 92, 10.1016/j.mad.2006.11.016

Frescas, 2017, Senescent cells expose and secrete an oxidized form of membrane-bound vimentin as revealed by a natural polyreactive antibody., Proc. Natl. Acad. Sci. U.S.A., 114, E1668, 10.1073/pnas.1614661114

Freund, 2012, Lamin B1 loss is a senescence-associated biomarker., Mol. Biol. Cell, 23, 2066, 10.1091/mbc.E11-10-0884

Freund, 2010, Inflammatory networks during cellular senescence: causes and consequences., Trends Mol. Med., 16, 238, 10.1016/j.molmed.2010.03.003

Freund, 2011, P38MAPK is a novel DNA damage response-independent regulator of the senescence-associated secretory phenotype., EMBO J., 30, 1536, 10.1038/emboj.2011.69

Fumagalli, 2012, Telomeric DNA damage is irreparable and causes persistent DNA-damage-response activation., Nat. Cell Biol., 14, 355, 10.1038/ncb2466

Funayama, 2006, Loss of linker histone H1 in cellular senescence., J. Cell Biol., 175, 869, 10.1083/jcb.200604005

Galanos, 2016, Chronic p53-independent p21 expression causes genomic instability by deregulating replication licensing., Nat. Cell Biol., 18, 777, 10.1038/ncb3378

Galluzzi, 2018, Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018., Cell Death Differ., 25, 486, 10.1038/s41418-017-0012-4

Gao, 2013, Cyclic [G(2′,5′)pA(3′,5′)p] is the metazoan second messenger produced by DNA-activated cyclic GMP-AMP synthase., Cell, 153, 1094, 10.1016/j.cell.2013.04.046

García-Prat, 2016, Autophagy maintains stemness by preventing senescence., Nature, 529, 37, 10.1038/nature16187

Garten, 2015, Physiological and pathophysiological roles of NAMPT and NAD metabolism., Nat. Rev. Endocrinol., 11, 535, 10.1038/nrendo.2015.117

Georgakilas, 2017, p21: a two-faced genome guardian., Trends Mol. Med., 23, 310, 10.1016/j.molmed.2017.02.001

Giaimo, 2012, Is cellular senescence an example of antagonistic pleiotropy?, Aging Cell, 11, 378, 10.1111/j.1474-9726.2012.00807.x

Gil, 2004, Polycomb CBX7 has a unifying role in cellular lifespan., Nat. Cell Biol., 6, 67, 10.1038/ncb1077

Gil, 2006, Regulation of the INK4b-ARF-INK4a tumour suppressor locus: all for one or one for all., Nat. Rev. Mol. Cell Biol., 7, 667, 10.1038/nrm1987

Gilbert, 2010, DNA damage-mediated induction of a chemoresistant niche., Cell, 143, 355, 10.1016/j.cell.2010.09.043

Gilbert, 2011, Chemotherapeutic resistance: surviving stressful situations., Cancer Res., 71, 5062, 10.1158/0008-5472.CAN-11-0277

Glück, 2017, Innate immune sensing of cytosolic chromatin fragments through cGAS promotes senescence., Nat. Cell Biol., 19, 1061, 10.1038/ncb3586

Gorgoulis, 2019, Cellular senescence: defining a path forward., Cell, 179, 813, 10.1016/j.cell.2019.10.005

Gorgoulis, 2010, Oncogene-induced senescence: the bright and dark side of the response., Curr. Opin. Cell Biol., 22, 816, 10.1016/j.ceb.2010.07.013

Gorgoulis, 2018, Integrating the DNA damage and protein stress responses during cancer development and treatment., J. Pathol., 246, 12, 10.1002/path.5097

Gould, 1997, Functions of mammalian Polycomb group and trithorax group related genes., Curr. Opin. Genet. Dev., 7, 488, 10.1016/S0959-437X(97)80075-5

Guerrero, 2016, HMGB2 holds the key to the senescence-associated secretory phenotype., J. Cell Biol., 215, 297, 10.1083/jcb.201610044

Guiley, 2015, Structural mechanisms of DREAM complex assembly and regulation., Genes Dev., 29, 961, 10.1101/gad.257568.114

Halazonetis, 2008, An oncogene-induced DNA damage model for cancer development., Science, 319, 1352, 10.1126/science.1140735

Hampel, 2004, Differential regulation of apoptotic cell death in senescent human cells., Exp. Gerontol., 39, 1713, 10.1016/j.exger.2004.05.010

Hanahan, 2011, Leading edge review hallmarks of cancer: the next generation., Cell, 144, 646, 10.1016/j.cell.2011.02.013

Hannon, 1994, Pl5INK4B is a potentia|effector of TGF-β-induced cell cycle arrest., Nature, 371, 257, 10.1038/371257a0

Hara, 1996, Regulation of p16CDKN2 expression and its implications for cell immortalization and senescence., Mol. Cell. Biol., 16, 859, 10.1128/MCB.16.3.859

Hardy, 2005, Transcriptional networks and cellular senescence in human mammary fibroblasts., Mol. Biol. Cell, 16, 943, 10.1091/mbc.E04-05-0392

Hari, 2019, The innate immune sensor Toll-like receptor 2 controls the senescence-associated secretory phenotype., Sci. Adv., 5, 10.1126/sciadv.aaw0254

Harrison, 2009, Rapamycin fed late in life extends lifespan in genetically heterogeneous mice., Nature, 460, 392, 10.1038/nature08221

Hashimoto, 2016, Elimination of p19ARF-expressing cells enhances pulmonary function in mice., JCI Insight, 1, 10.1172/jci.insight.87732

Hayflick, 1965, The limited in vitro lifetime of human diploid cell strains., Exp. Cell Res., 37, 614, 10.1016/0014-4827(65)90211-9

Hayflick, 1961, The serial cultivation of human diploid cell strains., Exp. Cell Res., 25, 585, 10.1016/0014-4827(61)90192-6

He, 2017, Senescence in health and disease., Cell, 169, 1000, 10.1016/j.cell.2017.05.015

Helman, 2016, p16 Ink4a-induced senescence of pancreatic beta cells enhances insulin secretion., Nat. Med., 22, 412, 10.1038/nm.4054

Herbig, 2006, Cellular senescence in aging primates., Science, 311, 10.1126/science.1122446

Herbig, 2004, Telomere shortening triggers senescence of human cells through a pathway involving ATM, p53, and p21CIP1, but not p16INK4a., Mol. Cell, 14, 501, 10.1016/S1097-2765(04)00256-4

Hermeking, 2010, The miR-34 family in cancer and apoptosis., Cell Death Differ., 17, 193, 10.1038/cdd.2009.56

Hernandez-Segura, 2017, Unmasking transcriptional heterogeneity in senescent cells., Curr. Biol., 27, 2652, 10.1016/j.cub.2017.07.033

Hernandez-Segura, 2018, Hallmarks of cellular senescence., Trends Cell Biol., 28, 436, 10.1016/j.tcb.2018.02.001

Herranz, 2015, mTOR regulates MAPKAPK2 translation to control the senescence-associated secretory phenotype., Nat. Cell Biol., 17, 1205, 10.1038/ncb3225

Herranz, 2018, Mechanisms and functions of cellular senescence Find the latest version: mechanisms and functions of cellular senescence., JCI J. Clin. Investig., 128, 1238, 10.1172/JCI95148

Hinze, 2018, Endocytosis in proliferating, quiescent and terminally differentiated cells., J. Cell Sci., 131, 10.1242/jcs.216804

Hoare, 2016, NOTCH1 mediates a switch between two distinct secretomes during senescence., Nat. Cell Biol., 18, 979, 10.1038/ncb3397

Horn, 2007, Coping with stress: multiple ways to activate p53., Oncogene, 26, 1306, 10.1038/sj.onc.1210263

Hu, 2010, Negative regulation of tumor suppressor p53 by MicroRNA miR-504., Mol. Cell, 38, 689, 10.1016/j.molcel.2010.05.027

Hu, 2018, GUARDIN is a p53-responsive long non-coding RNA that is essential for genomic stability., Nat. Cell Biol., 20, 492, 10.1038/s41556-018-0066-7

Hu, 2014, MicroRNA-29 induces cellular senescence in aging muscle through multiple signaling pathways., Aging (Albany NY), 6, 160, 10.18632/aging.100643

Hubackova, 2012, IL1-and TGFβ-Nox4 signaling, oxidative stress and DNA damage response are shared features of replicative, oncogene-induced, and drug-induced paracrine “Bystander senescence.”., Aging (Albany NY), 4, 932, 10.18632/aging.100520

Hubackova, 2010, Regulation of the PML tumor suppressor in drug-induced senescence of human normal and cancer cells by JAK/STAT-mediated signaling., Cell Cycle, 9, 3157, 10.4161/cc.9.15.12521

Hudgins, 2018, Age- and tissue-specific expression of senescence biomarkers in mice., Front. Genet., 9, 10.3389/fgene.2018.00059

Huggins, 2013, C/EBPγ suppresses senescence and inflammatory gene expression by heterodimerizing with C/EBPβ., Mol. Cell. Biol., 33, 3242, 10.1128/mcb.01674-12

Iannello, 2013, p53-dependent chemokine production by senescent tumor cells supports NKG2D-dependent tumor elimination by natural killer cells., J. Exp. Med., 210, 2057, 10.1084/jem.20130783

Imai, 2014, Crosstalk between the Rb pathway and AKT signaling forms a quiescence-senescence switch., Cell Rep., 7, 194, 10.1016/j.celrep.2014.03.006

Iness, 2019, The cell cycle regulatory DREAM complex is disrupted by high expression of oncogenic B-Myb., Oncogene, 38, 1080, 10.1038/s41388-018-0490-y

Ito, 2017, Spatial and temporal control of senescence., Trends Cell Biol., 27, 820, 10.1016/j.tcb.2017.07.004

Jacobs, 1999, The oncogene and Polycombgroup gene bmi-1 regulates cell proliferation and senescence through the ink4a locus., Nature, 397, 164, 10.1038/16476

Jascur, 2005, Regulation of p21WAF1/CIP1stability by WISp39, a Hsp90 binding TPR protein., Mol. Cell, 17, 237, 10.1016/j.molcel.2004.11.049

Jun, 2010, The matricellular protein CCN1 induces fibroblast senescence and restricts fibrosis in cutaneous wound healing., Nat. Cell Biol., 12, 676, 10.1038/ncb2070

Jun, 2011, Taking aim at the extracellular matrix: CCN proteins as emerging therapeutic targets., Nat. Rev. Drug Discov., 10, 945, 10.1038/nrd3599

Jurk, 2012, Postmitotic neurons develop a p21-dependent senescence-like phenotype driven by a DNA damage response., Aging Cell, 11, 996, 10.1111/j.1474-9726.2012.00870.x

Jurk, 2014, Chronic inflammation induces telomere dysfunction and accelerates ageing in mice., Nat. Commun., 2, 10.1038/ncomms5172

Kang, 2015, The DNA damage response induces inflammation and senescence by inhibiting autophagy of GATA4., Science, 349, 10.1126/science.aaa5612

Kang, 2011, Senescence surveillance of pre-malignant hepatocytes limits liver cancer development., Nature, 479, 547, 10.1038/nature10599

Karimian, 2016, Multiple functions of p21 in cell cycle, apoptosis and transcriptional regulation after DNA damage., DNA Repair (Amst)., 42, 63, 10.1016/j.dnarep.2016.04.008

Kastenhuber, 2017, Putting p53 in context., Cell, 170, 1062, 10.1016/j.cell.2017.08.028

Kasteri, 2018, Translation control by p53., Cancers (Basel)., 10, 1, 10.3390/cancers10050133

Kawasaki, 2014, Toll-like receptor signaling pathways., Front. Immunol., 5, 10.3389/fimmu.2014.00461

Kennedy, 2010, Senescent mouse cells fail to overtly regulate the HIRA histone chaperone and do not form robust Senescence Associated Heterochromatin Foci., Cell Div., 5, 10.1186/1747-1028-5-16

Kim, 2017, Long noncoding RNAs and RNA-binding proteins in oxidative stress, cellular senescence, and age-related diseases., Oxid. Med. Cell. Longev., 2017, 10.1155/2017/2062384

Kim, 2006, The regulation of INK4/ARF in cancer and aging., Cell, 127, 265, 10.1016/j.cell.2006.10.003

Kim, 2017, Senescent tumor cells lead the collective invasion in thyroid cancer., Nat. Commun., 8, 1, 10.1038/ncomms15208

Kirkwood, 2000, Why do we age?, Nature, 408, 233, 10.1038/35041682

Kobashigawa, 2019, Stress-induced cellular senescence contributes to chronic inflammation and cancer progression., Therm. Med., 35, 41, 10.3191/thermalmed.35.41

Korotchkina, 2010, The choice between p53-induced senescence and quiescence is determined in part by the mTOR pathway., Aging (Albany NY), 2, 344, 10.18632/aging.100160

Kortlever, 2006, Plasminogen activator inhibitor-1 is a critical downstream target of p53 in the induction of replicative senescence., Nat. Cell Biol., 8, 878, 10.1038/ncb1448

Kotake, 2011, Long non-coding RNA ANRIL is required for the PRC2 recruitment to and silencing of p15 INK4B tumor suppressor gene., Oncogene, 30, 1956, 10.1038/onc.2010.568

Kotake, 2009, DDB1-CUL4 and MLL1 mediate oncogene-lnduced p16 INK4aactivation., Cancer Res., 69, 1809, 10.1158/0008-5472.CAN-08-2739

Krishnamurthy, 2004, Ink4a/Arf expression is a biomarker of aging., J. Clin. Invest., 114, 1299, 10.1172/JCI22475

Krizhanovsky, 2008, Senescence of activated stellate cells limits liver fibrosis., Cell, 134, 657, 10.1016/j.cell.2008.06.049

Krtolica, 2001, Senescent fibroblasts promote epithelial cell growth and tumorigenesis: a link between cancer and aging., Proc. Natl. Acad. Sci. U.S.A., 98, 12072, 10.1073/pnas.211053698

Kruiswijk, 2015, P53 in survival, death and metabolic health: a lifeguard with a licence to kill., Nat. Rev. Mol. Cell Biol., 16, 393, 10.1038/nrm4007

Kruse, 2009, Modes of p53 regulation., Cell, 137, 609, 10.1016/j.cell.2009.04.050

Kuilman, 2010, The essence of senescence., Genes Dev., 24, 2463, 10.1101/gad.1971610

Kuilman, 2008, Oncogene-induced senescence relayed by an interleukin-dependent inflammatory network., Cell, 133, 1019, 10.1016/j.cell.2008.03.039

Kuilman, 2009, Senescence-messaging secretome: SMS-ing cellular stress., Nat. Rev. Cancer, 9, 81, 10.1038/nrc2560

Kurz, 2000, Senescence-associated (beta)-galactosidase reflects an increase in lysosomal mass during replicative ageing of human endothelial cells., J. Cell Sci., 3613, 10.1242/jcs.113.20.3613

Labaer, 1997, New functional activities for the p21 family of CDK inhibitors., Genes Dev., 11, 847, 10.1101/gad.11.7.847

Laberge, 2015, MTOR regulates the pro-tumorigenic senescence-associated secretory phenotype by promoting IL1A translation., Nat. Cell Biol., 17, 1049, 10.1038/ncb3195

Laiho, 1990, Growth inhibition by TGF-β linked to suppression of retinoblastoma protein phosphorylation., Cell, 62, 175, 10.1016/0092-8674(90)90251-9

Lal, 2008, p16INK4a translation suppressed by miR-24., PLoS One, 3, 10.1371/journal.pone.0001864

Lam, 2013, Forkhead box proteins: tuning forks for transcriptional harmony., Nat. Rev. Cancer, 13, 482, 10.1038/nrc3539

Lane, 1992, Cancer. p53, guardian of the genome., Nature, 358, 15, 10.1038/358015a0

Lapasset, 2011, Rejuvenating senescent and centenarian human cells by reprogramming through the pluripotent state., Genes Dev., 25, 2248, 10.1101/gad.173922.111

Lecot, 2016, Context-dependent effects of cellular senescence in cancer development., Br. J. Cancer, 114, 1180, 10.1038/bjc.2016.115

Lee, 2006, Senescence-associated β-galactosidase is lysosomal β-galactosidase., Aging Cell, 5, 187, 10.1111/j.1474-9726.2006.00199.x

Lehmann, 2008, Senescence-associated exosome release from human prostate cancer cells., Cancer Res., 68, 7864, 10.1158/0008-5472.CAN-07-6538

Lessard, 2018, Senescence-associated ribosome biogenesis defects contributes to cell cycle arrest through the Rb pathway., Nat. Cell Biol., 20, 789, 10.1038/s41556-018-0127-y

Levine, 2009, The first 30 years of p53: growing ever more complex., Nat. Rev. Cancer, 9, 749, 10.1038/nrc2723

Li, 2011, Regulatory mechanisms of tumor suppressor P16INK4A and their relevance to cancer., Biochemistry, 50, 5566, 10.1021/bi200642e

Li, 2018, The cGAS-cGAMP-STI NG pathway connects DNA damage to inflammation, senescence, and cancer., J. Exp. Med., 215, 1287, 10.1084/jem.20180139

Litovchick, 2011, DYRK1A protein kinase promotes quiescence and senescence through DREAM complex assembly., Genes Dev., 25, 801, 10.1101/gad.2034211

Litovchick, 2007, Evolutionarily conserved multisubunit RBL2/p130 and E2F4 protein complex represses human cell cycle-dependent genes in quiescence., Mol. Cell, 26, 539, 10.1016/j.molcel.2007.04.015

Liu, 2019, A tale of the good and bad: cell senescence in bone homeostasis and disease., Int. Rev. Cell Mol. Biol., 346, 97, 10.1016/bs.ircmb.2019.03.005

Loo, 2017, Gut microbiota promotes obesity-associated liver cancer through pge2-mediated suppression of antitumor immunity., Cancer Discov., 7, 522, 10.1158/2159-8290.CD-16-0932

Loo, 2020, Cellular senescence and senescence-associated secretory phenotype via the cGAS-STING signaling pathway in cancer., Cancer Sci., 111, 304, 10.1111/cas.14266

Lopes-Paciencia, 2019, The senescence-associated secretory phenotype and its regulation., Cytokine, 117, 15, 10.1016/j.cyto.2019.01.013

López-Otín, 2013, The hallmarks of aging., Cell, 153, 1194, 10.1016/j.cell.2013.05.039

Lujambio, 2013, Non-cell-autonomous tumor suppression by p53., Cell, 153, 449, 10.1016/j.cell.2013.03.020

Lukas, 2003, Distinct spatiotemporal dynamics of mammalian checkpoint regulators induced by DNA damage., Nat. Cell Biol., 5, 255, 10.1038/ncb945

Luteijn, 2019, SLC19A1 transports immunoreactive cyclic dinucleotides., Nature, 573, 434, 10.1038/s41586-019-1553-0

Maciejowski, 2017, Telomeres in cancer: tumour suppression and genome instability., Nat. Rev. Mol. Cell Biol., 18, 175, 10.1038/nrm.2016.171

Maciel-Barón, 2016, Senescence associated secretory phenotype profile from primary lung mice fibroblasts depends on the senescence induction stimuli., Age (Omaha)., 38, 1, 10.1007/s11357-016-9886-1

Malaquin, 2016, Keeping the senescence secretome under control: molecular reins on the senescence-associated secretory phenotype., Exp. Gerontol., 82, 39, 10.1016/j.exger.2016.05.010

Marcotte, 2004, Senescent fibroblasts resist apoptosis by downregulating caspase-3., Mech. Ageing Dev., 125, 777, 10.1016/j.mad.2004.07.007

Maréchal, 2013, DNA damage sensing by the ATM and ATR kinases., Cold Spring Harb. Perspect. Biol., 5, 10.1101/cshperspect.a012716

Martin, 2014, Ageing as developmental decay: insights from p16INK4a., Trends Mol. Med., 20, 667, 10.1016/j.molmed.2014.09.008

Martín-Caballero, 2001, Tumor susceptibility of p21waf1/cip1-deficient mice., Cancer Res., 61, 6234, 10.1158/0008-5472.can-10-0801

Martínez-Zamudio, 2020, AP-1 imprints a reversible transcriptional programme of senescent cells., Nat. Cell Biol., 22, 842, 10.1038/s41556-020-0529-5

McConnell, 1998, Inhibitors of cyclin-dependent kinases induce features of replicative senescence in early passage human diploid fibroblasts., Curr. Biol., 8, 351, 10.1016/S0960-9822(98)70137-X

McHugh, 2018, Senescence and aging: causes, consequences, and therapeutic avenues., J. Cell Biol., 217, 65, 10.1083/jcb.201708092

Mead, 2014, Proliferation assays (BrdU and EdU) on skeletal tissue sections., Methods Mol. Biol., 1130, 233, 10.1007/978-1-62703-989-5_17

Mikuła-Pietrasik, 2020, Mechanisms and significance of therapy-induced and spontaneous senescence of cancer cells., Cell. Mol. Life Sci., 77, 213, 10.1007/s00018-019-03261-8

Milanovic, 2018, Senescence-associated reprogramming promotes cancer stemness., Nature, 553, 96, 10.1038/nature25167

Mohamad Kamal, 2020, Aging of the cells: Insight into cellular senescence and detection Methods., Eur. J. Cell Biol., 99, 10.1016/j.ejcb.2020.151108

Morancho, 2015, Role of ADAM17 in the non-cell autonomous effects of oncogene-induced senescence., Breast Cancer Res., 17, 10.1186/s13058-015-0619-7

Moreno-Herrero, 2005, Mesoscale conformational changes in the DNA-repair complex Rad50/Mre11/Nbs1 upon binding DNA., Nature, 437, 440, 10.1038/nature03927

Müller, 2010, The central role of CDE/CHR promoter elements in the regulation of cell cycle-dependent gene transcription., FEBS J., 277, 877, 10.1111/j.1742-4658.2009.07508.x

Müller, 2012, The CHR promoter element controls cell cycle-dependent gene transcription and binds the DREAM and MMB complexes., Nucleic Acids Res., 40, 1561, 10.1093/nar/gkr793

Muñoz-Espín, 2013, XProgrammed cell senescence during mammalian embryonic development., Cell, 155, 1104, 10.1016/j.cell.2013.10.019

Muñoz-Espín, 2014, Cellular senescence: from physiology to pathology., Nat. Rev. Mol. Cell Biol., 15, 482, 10.1038/nrm3823

Myrianthopoulos, 2019, Senescence and senotherapeutics: a new field in cancer therapy., Pharmacol. Ther., 193, 31, 10.1016/j.pharmthera.2018.08.006

Nacarelli, 2019, NAD + metabolism governs the proinflammatory senescence-associated secretome., Nat. Cell Biol., 21, 397, 10.1038/s41556-019-0287-4

Nakamura, 2008, Both telomeric and non-telomeric DNA damage are determinants of mammalian cellular senescence., Epigenet. Chromatin, 1, 10.1186/1756-8935-1-6

Narita, 2006, A novel role for high-mobility group A proteins in cellular senescence and heterochromatin formation., Cell, 126, 503, 10.1016/j.cell.2006.05.052

Narita, 2003, Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence., Cell, 113, 703, 10.1016/S0092-8674(03)00401-X

Narita, 2011, Spatial coupling of mTOR and autophagy augments secretory phenotypes., Science, 332, 966, 10.1126/science.1205407

Nelson, 2018, The senescent bystander effect is caused by ROS-activated NF-κB signalling., Mech. Ageing Dev., 170, 30, 10.1016/j.mad.2017.08.005

Nelson, 2012, A senescent cell bystander effect: Senescence-induced senescence., Aging Cell, 11, 345, 10.1111/j.1474-9726.2012.00795.x

Noda, 1994, Cloning of senescent cell-derived inhibitors of dna synthesis using an expression screen., Exp. Cell Res., 211, 90, 10.1006/excr.1994.1063

Ohanna, 2011, Senescent cells develop a parp-1 and nuclear factor-κB-associated secretome (PNAS)., Genes Dev., 25, 1245, 10.1101/gad.625811

Ohtani, 2012, Cellular senescence: a double-edged sword in the fight against cancer., Exp. Dermatol., 21, 1, 10.1111/j.1600-0625.2012.01493.x

Olivier, 2010, TP53 mutations in human cancers: origins, consequences, and clinical use., Cold Spring Harb. Perspect. Biol., 2, 10.1101/cshperspect.a001008

Orjalo, 2009, Cell surface-bound IL-1α is an upstream regulator of the senescence-associated IL-6/IL-8 cytokine network., Proc. Natl. Acad. Sci. U.S.A., 106, 17031, 10.1073/pnas.0905299106

Overhoff, 2014, Cellular senescence mediated by p16INK4A-coupled miRNA pathways., Nucleic Acids Res., 42, 1606, 10.1093/nar/gkt1096

Özcan, 2016, Unbiased analysis of senescence associated secretory phenotype (SASP) to identify common components following different genotoxic stresses., Aging (Albany NY), 8, 1316, 10.18632/aging.100971

Panda, 2017, SASP regulation by noncoding RNA., Mech. Ageing Dev., 168, 37, 10.1016/j.mad.2017.05.004

Passos, 2010, Feedback between p21 and reactive oxygen production is necessary for cell senescence., Mol. Syst. Biol., 6, 10.1038/msb.2010.5

Patel, 2016, Derepression of hTERT gene expression promotes escape from oncogene-induced cellular senescence., Proc. Natl. Acad. Sci. U.S.A., 113, E5024, 10.1073/pnas.1602379113

Pavletich, 1999, Mechanisms of cyclin-dependent kinase regulation: structures of Cdks, their cyclin activators, and Cip and INK4 inhibitors., J. Mol. Biol., 287, 821, 10.1006/jmbi.1999.2640

Pazolli, 2012, Chromatin remodeling underlies the senescence-associated secretory phenotype of tumor stromal fibroblasts that supports cancer progression., Cancer Res., 72, 2251, 10.1158/0008-5472.CAN-11-3386

Peng, 1997, Mitotic and G2 checkpoint control: regulation of 14-3-3 protein binding by phosphorylation of Cdc25C on serine-216., Science, 277, 1501, 10.1126/science.277.5331.1501

Petrova, 2016, Small molecule compounds that induce cellular senescence., Aging Cell, 15, 999, 10.1111/acel.12518

Philipot, 2014, P16INK4a and its regulator miR-24 link senescence and chondrocyte terminal differentiation-associated matrix remodeling in osteoarthritis., Arthritis Res. Ther., 16, 10.1186/ar4494

Ping, 2006, Cytoplasmic expression of p21CIP1/WAF1 is correlated with IKKbeta overexpression in human breast cancers., Int. J. Oncol., 29, 1103, 10.3892/ijo.29.5.1103

Puvvula, 2014, Long noncoding RNA PANDA and scaffold-attachment-factor SAFA control senescence entry and exit., Nat. Commun., 5, 1, 10.1038/ncomms6323

Quaas, 2012, p53 can repress transcription of cell cycle genes through a p21WAF1/CIP1-dependent switch from MMB to DREAM protein complex binding at CHR promoter elements., Cell Cycle, 11, 4661, 10.4161/cc.22917

Ramakrishna, 2012, Role of cellular senescence in hepatic wound healing and carcinogenesis., Eur. J. Cell Biol., 91, 739, 10.1016/j.ejcb.2012.08.002

Ramos, 2020, Vimentin as a multifaceted player and potential therapeutic target in viral infections., Int. J. Mol. Sci., 21, 1, 10.3390/ijms21134675

Rao, 2016, SASP: tumor suppressor or promoter? Yes!, Trends Cancer, 2, 676, 10.1016/j.trecan.2016.10.001

Ribeiro, 2013, ZRF1 controls oncogene-induced senescence through the INK4-ARF locus., Oncogene, 32, 2161, 10.1038/onc.2012.241

Ritchie, 2019, SLC19A1 is an importer of the immunotransmitter cGAMP., Mol. Cell, 75, 372, 10.1016/j.molcel.2019.05.006

Ritschka, 2017, The senescence-associated secretory phenotype induces cellular plasticity and tissue regeneration., Genes Dev., 31, 172, 10.1101/gad.290635.116

Rodier, 2011, Four faces of cellular senescence., J. Cell Biol., 192, 547, 10.1083/jcb.201009094

Rodier, 2009, Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion., Nat. Cell Biol., 11, 973, 10.1038/ncb1909

Rodier, 2011, DNA-SCARS: distinct nuclear structures that sustain damage-induced senescence growth arrest and inflammatory cytokine secretion., J. Cell Sci., 124, 68, 10.1242/jcs.071340

Rovillain, 2011, An RNA interference screen for identifying downstream effectors of the p53 and pRB tumour suppressor pathways involved in senescence., BMC Genomics, 12, 10.1186/1471-2164-12-355

Ryu, 2007, Failure of stress-induced downregulation of Bcl-2 contributes to apoptosis resistance in senescent human diploid fibroblasts., Cell Death Differ., 14, 1020, 10.1038/sj.cdd.4402091

Sadaie, 2013, Redistribution of the Lamin B1 genomic binding profile affects rearrangement of heterochromatic domains and SAHF formation during senescence., Genes Dev., 27, 1800, 10.1101/gad.217281.113

Sadasivam, 2013, The DREAM complex: master coordinator of cell cycle-dependent gene expression., Nat. Rev. Cancer, 13, 585, 10.1038/nrc3556

Sadasivam, 2012, The MuvB complex sequentially recruits B-Myb and FoxM1 to promote mitotic gene expression., Genes Dev., 26, 474, 10.1101/gad.181933.111

Salama, 2014, Cellular senescence and its effector programs., Genes Dev., 28, 99, 10.1101/gad.235184.113

Saleh, 2018, Non-cell autonomous effects of the senescence-associated secretory phenotype in cancer therapy., Front. Oncol., 8, 10.3389/fonc.2018.00164

Saleh, 2019, Tumor cell escape from therapy-induced senescence as a model of disease recurrence after dormancy., Cancer Res., 79, 1044, 10.1158/0008-5472.CAN-18-3437

Sanders, 2013, Histone modifications in senescence-associated resistance to apoptosis by oxidative stress., Redox Biol., 1, 8, 10.1016/j.redox.2012.11.004

Sapieha, 2018, Cellular senescence in postmitotic cells: beyond growth arrest., Trends Cell Biol., 28, 595, 10.1016/j.tcb.2018.03.003

Schmit, 2009, LIN54 is an essential core subunit of the DREAM/LINC complex that binds to the cdc2 promoter in a sequence-specific manner., FEBS J., 276, 5703, 10.1111/j.1742-4658.2009.07261.x

Schmit, 2007, LINC, a human complex that is related to pRB-containing complexes in invertebrates regulates the expression of G2/M genes., Cell Cycle, 6, 1903, 10.4161/cc.6.15.4512

Schosserer, 2017, The dual role of cellular senescence in developing tumors and their response to cancer therapy., Front. Oncol., 7, 10.3389/fonc.2017.00278

Schroder, 2010, The inflammasomes., Cell, 140, 821, 10.1016/j.cell.2010.01.040

Serrano, 1993, A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4., Nature, 366, 704, 10.1038/366704a0

Severino, 2013, Insulin-like growth factor binding proteins 4 and 7 released by senescent cells promote premature senescence in mesenchymal stem cells., Cell Death Dis., 4, 10.1038/cddis.2013.445

Shah, 2013, Lamin B1 depletion in senescent cells triggers large-scale changes in gene expression and the chromatin landscape., Genes Dev., 27, 1787, 10.1101/gad.223834.113

Sharpless, 2005, INK4a/ARF: a multifunctional tumor suppressor locus., Mutat. Res., 576, 22, 10.1016/j.mrfmmm.2004.08.021

Sharpless, 2006, The mighty mouse: genetically engineered mouse models in cancer drug development., Nat. Rev. Drug Discov., 5, 741, 10.1038/nrd2110

Sharpless, 2015, Forging a signature of in vivo senescence., Nat. Rev. Cancer, 15, 397, 10.1038/nrc3960

Shay, 1991, A role for both RB and p53 in the regulation of human cellular senescence., Exp. Cell Res., 196, 33, 10.1016/0014-4827(91)90453-2

Shay, 2019, Telomeres and telomerase: three decades of progress., Nat. Rev. Genet., 20, 299, 10.1038/s41576-019-0099-1

Sherr, 2000, The pezcoller lecture: cancer cell cycles revisited – unit 4., Cancer Res., 60, 3689

Song, 2020, Senescent cells: emerging targets for human aging and age-related diseases., Trends Biochem. Sci., 45, 578, 10.1016/j.tibs.2020.03.008

Soto-Gamez, 2017, Therapeutic interventions for aging: the case of cellular senescence., Drug Discov. Today, 22, 786, 10.1016/j.drudis.2017.01.004

Stein, 1999, Differential roles for cyclin-dependent kinase inhibitors p21 and p16 in the mechanisms of senescence and differentiation in human fibroblasts., Mol. Cell. Biol., 19, 2109, 10.1128/MCB.19.3.2109

Stilmann, 2009, A nuclear poly(ADP-Ribose)-dependent signalosome confers DNA damage-induced IκB kinase activation., Mol. Cell, 36, 365, 10.1016/j.molcel.2009.09.032

Storer, 2013, XSenescence is a developmental mechanism that contributes to embryonic growth and patterning., Cell, 155, 1119, 10.1016/j.cell.2013.10.041

Stow, 2013, Intracellular trafficking and secretion of inflammatory cytokines., Cytokine Growth Factor Rev., 24, 227, 10.1016/j.cytogfr.2013.04.001

Stracker, 2004, The Mre11 complex and the metabolism of chromosome breaks: the importance of communicating and holding things together., DNA Repair. (Amst.), 3, 845, 10.1016/j.dnarep.2004.03.014

Strowig, 2012, Inflammasomes in health and disease., Nature, 481, 278, 10.1038/nature10759

Suh, 2018, MicroRNA controls of cellular senescence., BMB Rep., 51, 493, 10.5483/BMBRep.2018.51.10.209

Sulli, 2012, Crosstalk between chromatin state and DNA damage response in cellular senescence and cancer., Nat. Rev. Cancer, 12, 709, 10.1038/nrc3344

Sun, 2013, Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway., Science, 339, 786, 10.1126/science.1232458

Sun, 2018, Cellular senescence: the sought or the unwanted?, Trends Mol. Med., 24, 871, 10.1016/j.molmed.2018.08.002

Suram, 2012, Oncogene-induced telomere dysfunction enforces cellular senescence in human cancer precursor lesions., EMBO J., 31, 2839, 10.1038/emboj.2012.132

Surova, 2013, Various modes of cell death induced by DNA damage., Oncogene, 32, 3789, 10.1038/onc.2012.556

Swanson, 2013, Higher-order unfolding of satellite heterochromatin is a consistent and early event in cell senescence., J. Cell Biol., 203, 929, 10.1083/jcb.201306073

Taguchi, 2017, Unveiling the Role of Senescence-Induced Cellular Plasticity., Cell Stem Cell, 20, 293, 10.1016/j.stem.2017.02.001

Takahashi, 2012, DNA damage signaling triggers degradation of histone methyltransferases through APC/CCdh1in senescent cells., Mol. Cell, 45, 123, 10.1016/j.molcel.2011.10.018

Takahashi, 2018, Downregulation of cytoplasmic DNases is implicated in cytoplasmic DNA accumulation and SASP in senescent cells., Nat. Commun., 9, 1, 10.1038/s41467-018-03555-8

Takasugi, 2017, Small extracellular vesicles secreted from senescent cells promote cancer cell proliferation through EphA2., Nat. Commun., 8, 10.1038/ncomms15728

Tasdemir, 2016, BRD4 connects enhancer remodeling to senescence immune surveillance., Cancer Discov., 6, 613, 10.1158/2159-8290.CD-16-0217

Toso, 2014, Enhancing chemotherapy efficacy in pten-deficient prostate tumors by activating the senescence-associated antitumor immunity., Cell Rep., 9, 75, 10.1016/j.celrep.2014.08.044

Toussaint, 2002, From the Hayflick mosaic to the mosaics of ageing. Role of stress-induced premature senescence in human ageing., Int. J. Biochem. Cell Biol., 34, 1415, 10.1016/S1357-2725(02)00034-1

Umbreit, 2017, Cancer biology: Genome jail-break triggers lockdown., Nature, 550, 340, 10.1038/nature24146

Van Deursen, 2014, The role of senescent cells in ageing., Nature, 509, 439, 10.1038/nature13193

van Deursen, 2019, Senolytic therapies for healthy longevity., Science, 364, 636, 10.1126/science.aaw1299

Van Lohuizen, 1998, Functional analysis of mouse Polycomb group genes., Cell. Mol. Life Sci., 54, 71, 10.1007/s000180050126

Verdin, 2015, NAD+ in aging, metabolism, and neurodegeneration., Science, 350, 1208, 10.1126/science.aac4854

von Kobbe, 2018, Cellular senescence: a view throughout organismal life., Cell. Mol. Life Sci., 75, 3553, 10.1007/s00018-018-2879-8

von Zglinicki, 2020, Senescence in Post-Mitotic Cells: A Driver of Aging?, Antioxid. Redox Signal., 34, 308, 10.1089/ars.2020.8048

Vougas, 2019, Machine learning and data mining frameworks for predicting drug response in cancer: An overview and a novel in silico screening process based on association rule mining., Pharmacol. Ther., 203, 10.1016/j.pharmthera.2019.107395

Vousden, 2009, Blinded by the Light: The Growing Complexity of p53., Cell, 137, 413, 10.1016/j.cell.2009.04.037

Wade Harper, 1993, The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases., Cell, 75, 805, 10.1016/0092-8674(93)90499-G

Wajapeyee, 2008, Oncogenic BRAF Induces Senescence and Apoptosis through Pathways Mediated by the Secreted Protein IGFBP7., Cell, 132, 363, 10.1016/j.cell.2007.12.032

Wang, 2020, Senescent Cells in Cancer Therapy: Friends or Foes?, Trends in Cancer, 6, 838, 10.1016/j.trecan.2020.05.004

Wang, 2009, DNA damage response and cellular senescence in tissues of aging mice., Aging Cell, 8, 311, 10.1111/j.1474-9726.2009.00481.x

Wang, 1995, Senescent Human Fibroblasts Resist Programmed Cell Death, and Failure to Suppress bell Is Involved., Cancer Res., 55, 2284

Webley, 2000, Posttranslational modifications of p53 in replicative senescence overlapping but distinct from those induced by DNA damage., Mol. Cell. Biol., 20, 2803, 10.1128/MCB.20.8.2803-2808.2000

Weiss, 2002, Hus1 acts upstream of Chk1 in a mammalian DNA damage response pathway., Curr. Biol., 12, 73, 10.1016/S0960-9822(01)00626-1

Welcker, 1998, p21(WAF1/CIP1) mutants deficient in inhibiting cyclin-dependent kinases (CDKs) can promote assembly of active cyclin D/CDK4(6) complexes in human tumor cells., Cancer Res., 58, 5053

Whittaker, 2017, Inhibitors of cyclin-dependent kinases as cancer therapeutics., Pharmacol. Ther., 173, 83, 10.1016/j.pharmthera.2017.02.008

Wiedemeyer, 2018, “Resistance Mechanisms to Cyclin-Dependent Kinase Inhibitors,” in., 181, 10.1007/978-3-319-67932-7_8

Wiley, 2017, Analysis of individual cells identifies cell-to-cell variability following induction of cellular senescence., Aging Cell, 16, 1043, 10.1111/acel.12632

Wiley, 2016, Mitochondrial dysfunction induces senescence with a distinct secretory phenotype., Cell Metab., 23, 303, 10.1016/j.cmet.2015.11.011

Williams, 1957, Pleiotropy, natural selection, and the evolution of senescence., Evolution (N. Y)., 11, 398, 10.1111/j.1558-5646.1957.tb02911.x

Wu, 2013, Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA., Science, 339, 826, 10.1126/science.1229963

Xiao, 2011, MiR-605 joins p53 network to form a p53:miR-605:Mdm2 positive feedback loop in response to stress., EMBO J., 30, 524, 10.1038/emboj.2010.347

Xie, 2018, DNA Methylation Patterns Separate Senescence from Transformation Potential and Indicate Cancer Risk., Cancer Cell, 33, 309.e, 10.1016/j.ccell.2018.01.008

Xu, , Targeting senescent cells enhances adipogenesis and metabolic function in old age., Elife, 4, 10.7554/eLife.12997

Xu, , JAK inhibition alleviates the cellular senescence-associated secretory phenotype and frailty in old age., Proc. Natl. Acad. Sci. U. S. A., 112, E6301, 10.1073/pnas.1515386112

Xu, 2019, Targeting amphiregulin (AREG) derived from senescent stromal cells diminishes cancer resistance and averts programmed cell death 1 ligand (PD-L1)-mediated immunosuppression., Aging Cell, 18, 10.1111/acel.13027

Xu, 2019, The p53/miRNAs/Ccna2 pathway serves as a novel regulator of cellular senescence: Complement of the canonical p53/p21 pathway., Aging Cell, 18, 10.1111/acel.12918

Xue, 2007, Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas., Nature, 445, 656, 10.1038/nature05529

Yamakoshi, 2009, Real-time in vivo imaging of p16 Ink4a reveals cross talk with p53., J. Cell Biol., 186, 393, 10.1083/jcb.200904105

Yang, 2017, cGAS is essential for cellular senescence., Proc. Natl. Acad. Sci., 114, E4612, 10.1073/pnas.1705499114

Yap, 2010, Molecular Interplay of the Noncoding RNA ANRIL and Methylated Histone H3 Lysine 27 by Polycomb CBX7 in Transcriptional Silencing of INK4a., Mol. Cell, 38, 662, 10.1016/j.molcel.2010.03.021

Yoshimoto, 2013, Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome., Nature, 499, 97, 10.1038/nature12347

Young, 2013, Cell senescence as both a dynamic and a static phenotype., Methods Mol. Biol., 965, 1, 10.1007/978-1-62703-239-1_1

Yun, 2015, Recurrent turnover of senescent cells during regeneration of a complex structure., Elife, 4, 1, 10.7554/eLife.05505

Zhang, 2018, The senescence-associated secretory phenotype is potentiated by feedforward regulatory mechanisms involving Zscan4 and TAK1., Nat. Commun., 9, 10.1038/s41467-018-04010-4

Zhang, 2000, Exit from G1 and S phase of the cell cycle is regulated by repressor complexes containing HDAC-Rb-hSWI/SNF and RB-hSWI/SNF., Cell, 101, 79, 10.1016/S0092-8674(00)80625-X

Zhang, 2006, p16INK4a modulates p53 in primary human mammary epithelial cells., Cancer Res., 66, 10325, 10.1158/0008-5472.CAN-06-1594

Zhang, 2013, Cyclic GMP-AMP containing mixed Phosphodiester linkages is an endogenous high-affinity ligand for STING., Mol. Cell, 51, 226, 10.1016/j.molcel.2013.05.022

Zhao, 2018, Naked mole rats can undergo developmental, oncogene-induced and DNA damage-induced cellular senescence., Proc. Natl. Acad. Sci. U.S.A., 115, 1801, 10.1073/pnas.1721160115

Zhu, 2015, The Achilles’ heel of senescent cells: from transcriptome to senolytic drugs., Aging Cell, 14, 644, 10.1111/acel.12344

Zirkel, 2018, HMGB2 loss upon senescence entry disrupts genomic organization and induces CTCF clustering across cell types., Mol. Cell, 70, 730.e, 10.1016/j.molcel.2018.03.030

Zou, 2003, Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes., Science, 300, 1542, 10.1126/science.1083430