References
- Hayflick L (1965) The limited in vitro lifetime of human diploid cell strains. Exp Cell Res 37, 614-636 https://doi.org/10.1016/0014-4827(65)90211-9
- Campisi J (2013) Aging, cellular senescence, and cancer. Annu Rev Physiol 75, 685-705 https://doi.org/10.1146/annurev-physiol-030212-183653
- Deng Y and Chang S (2007) Role of telomeres and telomerase in genomic instability, senescence and cancer. Lab Invest 87, 1071-1076 https://doi.org/10.1038/labinvest.3700673
- Munoz-Espin D, Canamero M, Maraver A et al (2013) Programmed cell senescence during mammalian embryonic development. Cell 155, 1104-1118 https://doi.org/10.1016/j.cell.2013.10.019
- Storer M, Mas A, Robert-Moreno A et al (2013) Senescence is a developmental mechanism that contributes to embryonic growth and patterning. Cell 155, 1119-1130 https://doi.org/10.1016/j.cell.2013.10.041
- Campisi J (2014) Cell biology: The beginning of the end. Nature 505, 35-36 https://doi.org/10.1038/nature12844
- Acosta JC and Gil J (2012) Senescence: a new weapon for cancer therapy. Trends Cell Biol 22, 211-219 https://doi.org/10.1016/j.tcb.2011.11.006
- Itahana K, Campisi J and Dimri GP (2004) Mechanisms of cellular senescence in human and mouse cells. Biogerontology 5, 1-10 https://doi.org/10.1023/B:BGEN.0000017682.96395.10
- Chang BD, Broude EV, Dokmanovic M et al (1999) A senescence-like phenotype distinguishes tumor cells that undergo terminal proliferation arrest after exposure to anticancer agents. Cancer Res 59, 3761-3767
- Chang BD, Xuan Y, Broude EV et al (1999) Role of p53 and p21waf1/cip1 in senescence-like terminal proliferation arrest induced in human tumor cells by chemotherapeutic drugs. Oncogene 18, 4808-4818 https://doi.org/10.1038/sj.onc.1203078
- Lee M and Lee JS (2014) Exploiting tumor cell senescence in anticancer therapy. BMB Rep 47, 51-59 https://doi.org/10.5483/BMBRep.2014.47.2.005
- Hernandez-Segura A, Nehme J and Demaria M (2018) Hallmarks of Cellular Senescence. Trends Cell Biol 28, 436-453 https://doi.org/10.1016/j.tcb.2018.02.001
- Myrianthopoulos V, Evangelou K, Vasileiou PVS et al (2019) Senescence and senotherapeutics: a new field in cancer therapy. Pharmacol Ther 193, 31-49 https://doi.org/10.1016/j.pharmthera.2018.08.006
- Herranz N and Gil J (2018) Mechanisms and functions of cellular senescence. J Clin Invest 128, 1238-1246 https://doi.org/10.1172/JCI95148
- d'Adda di Fagagna F, Reaper PM, Clay-Farrace L et al (2003) A DNA damage checkpoint response in telomereinitiated senescence. Nature 426, 194-198 https://doi.org/10.1038/nature02118
- Suram A, Kaplunov J, Patel PL et al (2012) Oncogeneinduced telomere dysfunction enforces cellular senescence in human cancer precursor lesions. EMBO J 31, 2839-2851 https://doi.org/10.1038/emboj.2012.132
- Shiloh Y (2006) The ATM-mediated DNA-damage response: taking shape. Trends Biochem Sci 31, 402-410 https://doi.org/10.1016/j.tibs.2006.05.004
- Celeste A, Petersen S, Romanienko PJ et al (2002) Genomic instability in mice lacking histone H2AX. Science 296, 922-927 https://doi.org/10.1126/science.1069398
- d'Adda di Fagagna F (2008) Living on a break: cellular senescence as a DNA-damage response. Nat Rev Cancer 8, 512-522 https://doi.org/10.1038/nrc2440
- Lukas C, Falck J, Bartkova J, Bartek J and Lukas J (2003) Distinct spatiotemporal dynamics of mammalian checkpoint regulators induced by DNA damage. Nat Cell Biol 5, 255-260 https://doi.org/10.1038/ncb945
- Turenne GA, Paul P, Laflair L and Price BD (2001) Activation of p53 transcriptional activity requires ATM's kinase domain and multiple N-terminal serine residues of p53. Oncogene 20, 5100-5110 https://doi.org/10.1038/sj.onc.1204665
- Acosta JC, Banito A, Wuestefeld T et al (2013) A complex secretory program orchestrated by the inflammasome controls paracrine senescence. Nat Cell Biol 15, 978-990 https://doi.org/10.1038/ncb2784
- Yoshimoto S, Loo TM, Atarashi K et al (2013) Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome. Nature 499, 97-101 https://doi.org/10.1038/nature12347
-
Ohanna M, Giuliano S, Bonet C et al (2011) Senescent cells develop a PARP-1 and nuclear factor-
${\kappa}B$ -associated secretome (PNAS). Genes Dev 25, 1245-1261 https://doi.org/10.1101/gad.625811 - Wiley CD, Velarde MC, Lecot P et al (2016) Mitochondrial dysfunction induces senescence with a distinct secretory phenotype. Cell Metab 23, 303-314 https://doi.org/10.1016/j.cmet.2015.11.011
- Kang C, Xu Q, Martin TD et al (2015) The DNA damage response induces inflammation and senescence by inhibiting autophagy of GATA4. Science 349, aaa5612 https://doi.org/10.1126/science.aaa5612
- Kuilman T and Peeper DS (2008) Oncogene-induced senescence relayed by an interleukin-dependent inflammatory network. Cell 133, 1019-1031 https://doi.org/10.1016/j.cell.2008.03.039
- Acosta JC, O'Loghlen A, Banito A et al (2008) Chemokine signaling via the CXCR2 receptor reinforces senescence. Cell 133, 1006-1018 https://doi.org/10.1016/j.cell.2008.03.038
- Laberge RM, Sun Y, Orjalo AV et al (2015) MTOR regulates the pro-tumorigenic senescence-associated secretory phenotype by promoting IL1A translation. Nat Cell Biol 17, 1049-1061 https://doi.org/10.1038/ncb3195
- Herranz N, Gallage S, Mellone M et al (2015) mTOR regulates MAPKAPK2 translation to control the senescenceassociated secretory phenotype. Nat Cell Biol 17, 1205-1217 https://doi.org/10.1038/ncb3225
- Hayakawa T, Iwai M, Aoki S et al (2015) SIRT1 suppresses the senescence-associated secretory phenotype through epigenetic gene regulation. PLoS One 10, e0116480 https://doi.org/10.1371/journal.pone.0116480
- Chen H, Ruiz PD, McKimpson WM et al (2015) MacroH2A1 and ATM play opposing roles in paracrine senescence and the senescence-associated secretory phenotype. Mol Cell 59, 719-731 https://doi.org/10.1016/j.molcel.2015.07.011
- Capell BC, Drake AM, Zhu J et al (2016) MLL1 is essential for the senescence-associated secretory phenotype. Genes Dev 30, 321-336 https://doi.org/10.1101/gad.271882.115
-
Jung SH, Lee M, Park HA et al (2018) Integrin
${\alpha}6{\beta}4$ -Src-AKT signaling induces cellular senescence by counteracting apoptosis in irradiated tumor cells and tissues. Cell Death Differ 26, 245-259 https://doi.org/10.1038/s41418-018-0114-7 - Ohno-Iwashita Y, Shimada Y, Hayashi M and Inomata M (2010) Plasma membrane microdomains in aging and disease. Geriatr Gerontol Int 10, S41-52 https://doi.org/10.1111/j.1447-0594.2010.00600.x
-
Kurz DJ, Decary S, Hong Y and Erusalimsky JD (2000) Senescence-associated
${\beta}$ -galactosidase reflects an increase in lysosomal mass during replicative ageing of human endothelial cells. J Cell Sci 113, 3613-3622 https://doi.org/10.1242/jcs.113.20.3613 - Sadaie M, Salama R, Carroll T et al (2013) Redistribution of the Lamin B1 genomic binding profile affects rearrangement of heterochromatic domains and SAHF formation during senescence. Genes Dev 27, 1800-1808 https://doi.org/10.1101/gad.217281.113
- Salama R, Sadaie M, Hoare M and Narita M (2014) Cellular senescence and its effector programs. Genes Dev 28, 99-114 https://doi.org/10.1101/gad.235184.113
- Nardella C, Clohessy JG, Alimonti A and Pandolfi PP (2011) Pro-senescence therapy for cancer treatment. Nat Rev Cancer 11, 503-511 https://doi.org/10.1038/nrc3057
- Kim WY and Sharpless NE (2006) The regulation of INK4/ARF in cancer and aging. Cell 127, 265-275 https://doi.org/10.1016/j.cell.2006.10.003
- Bracken AP, Kleine-Kohlbrecher D, Dietrich N et al (2007) The Polycomb group proteins bind throughout the INK4A-ARF locus and are disassociated in senescent cells. Genes Dev 21, 525-530 https://doi.org/10.1101/gad.415507
- Alcorta DA, Xiong Y, Phelps D, Hannon G, Beach D and Barrett JC (1996) Involvement of the cyclin-dependent kinase inhibitor p16 (INK4a) in replicative senescence of normal human fibroblasts. Pro Natl Acad Sci U S A 93, 13742-13747 https://doi.org/10.1073/pnas.93.24.13742
- Wiley CD and Campisi J (2016) From ancient pathways to aging cells-connecting metabolism and cellular senescence. Cell Metab 23, 1013-1021 https://doi.org/10.1016/j.cmet.2016.05.010
- Jones RG, Plas DR, Kubek S et al (2005) AMP-activated protein kinase induces a p53-dependent metabolic checkpoint. Mol Cell 18, 283-293 https://doi.org/10.1016/j.molcel.2005.03.027
- Wang W, Yang X, Lopez de Silanes I, Carling D and Gorospe M (2003) Increased AMP:ATP ratio and AMP-activated protein kinase activity during cellular senescence linked to reduced HuR function. J Biol Chem 278, 27016-27023 https://doi.org/10.1074/jbc.M300318200
- Tran D, Bergholz J, Zhang H et al (2014) Insulin-like growth factor-1 regulates the SIRT1-p53 pathway in cellular senescence. Aging Cell 13, 669-678 https://doi.org/10.1111/acel.12219
- Angelini F, Pagano F, Bordin A et al (2017) Getting old through the blood: Circulating molecules in aging and senescence of cardiovascular regenerative cells. Front Cardiovasc Med 4, 62 https://doi.org/10.3389/fcvm.2017.00062
- Michishita E, Park JY, Burneskis JM, Barrett JC and Horikawa I (2005) Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins. Mol Biol Cell 16, 4623-4635 https://doi.org/10.1091/mbc.e05-01-0033
- Ota H, Tokunaga E, Chang K et al (2006) Sirt1 inhibitor, Sirtinol, induces senescence-like growth arrest with attenuated Ras-MAPK signaling in human cancer cells. Oncogene 25, 176-185 https://doi.org/10.1038/sj.onc.1209049
- Huang J, Gan Q, Han L et al (2008) SIRT1 overexpression antagonizes cellular senescence with activated ERK/S6k1 signaling in human diploid fibroblasts. PLoS One 3, e1710 https://doi.org/10.1371/journal.pone.0001710
- Langley E, Pearson M, Faretta M et al (2002) Human SIR2 deacetylates p53 and antagonizes PML/p53-induced cellular senescence. EMBO J 21, 2383-2396 https://doi.org/10.1093/emboj/21.10.2383
- Ong ALC and Ramasamy TS (2018) Role of Sirtuin1-p53 regulatory axis in aging, cancer and cellular reprogramming. Ageing Res Rev 43, 64-80 https://doi.org/10.1016/j.arr.2018.02.004
- Blume-Jensen P and Hunter T (2001) Oncogenic kinase signalling. Nature 411, 355-365 https://doi.org/10.1038/35077225
- Jung SH, Hwang HJ, Kang D et al (2018) mTOR kinase leads to PTEN-loss-induced cellular senescence by phosphorylating p53. Oncogene [Epub ahead of print]
- Schneider JL and Cuervo AM (2014) Autophagy and human disease: emerging themes. Curr Opin Genet Dev 26, 16-23 https://doi.org/10.1016/j.gde.2014.04.003
- Chang J, Lee S and Blackstone C (2014) Spastic paraplegia proteins spastizin and spatacsin mediate autophagic lysosome reformation. J Clin Invest 124, 5249-5262 https://doi.org/10.1172/JCI77598
- Gewirtz DA (2013) Autophagy and senescence: A partnership in search of definition. Autophagy 9, 808 https://doi.org/10.4161/auto.23922
- Kang C and Elledge SJ (2016) How autophagy both activates and inhibits cellular senescence. Autophagy 12, 898-899 https://doi.org/10.1080/15548627.2015.1121361
- Young AR, Narita M, Ferreira M et al (2009) Autophagy mediates the mitotic senescence transition. Genes Dev 23, 798-803 https://doi.org/10.1101/gad.519709
- Mosieniak G, Adamowicz M, Alster O et al (2012) Curcumin induces permanent growth arrest of human colon cancer cells: link between senescence and autophagy. Mech Ageing Dev 133, 444-455 https://doi.org/10.1016/j.mad.2012.05.004
- Wang Y, Wang XD, Lapi E et al (2012) Autophagic activity dictates the cellular response to oncogenic RAS. Proc Natl Acad Sci U S A 109, 13325-13330 https://doi.org/10.1073/pnas.1120193109
- Kim BC, Yoo HJ, Lee HC et al (2014) Evaluation of premature senescence and senescence biomarkers in carcinoma cells and xenograft mice exposed to single or fractionated irradiation. Oncol Rep 31, 2229-2235 https://doi.org/10.3892/or.2014.3069
- Ewald JA, Desotelle JA, Wilding G and Jarrard DF (2010) Therapy-induced senescence in cancer. J Natl Cancer Inst 102, 1536-1546 https://doi.org/10.1093/jnci/djq364
- Ovadya Y and Krizhanovsky V (2018) Strategies targeting cellular senescence. J Clin Invest 128, 1247-1254 https://doi.org/10.1172/JCI95149
- Yosef R, Pilpel N, Papismadov N et al (2017) p21 maintains senescent cell viability under persistent DNA damage response by restraining JNK and caspase signaling. EMBO J 36, 2280-2295 https://doi.org/10.15252/embj.201695553
- Vassilev LT, Vu BT, Graves B et al (2004) In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science 303, 844-848 https://doi.org/10.1126/science.1092472
- Alimonti A, Nardella C, Chen Z et al (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, 681-693 https://doi.org/10.1172/JCI40535
- Gembarska A, Luciani F, Fedele C et al (2012) MDM4 is a key therapeutic target in cutaneous melanoma. Nat Med 18, 1239-1247 https://doi.org/10.1038/nm.2863
- Harajly M, Zalzali H, Nawaz Z et al (2016) p53 restoration in induction and maintenance of senescence: Differential effects in premalignant and malignant tumor cells. Mol Cell Biol 36, 438-451 https://doi.org/10.1128/MCB.00747-15
- Baar MP, Brandt RMC, Putavet DA et al (2017) Targeted apoptosis of senescent cells restores tissue homeostasis in response to chemotoxicity and aging. Cell 169, 132-147 https://doi.org/10.1016/j.cell.2017.02.031
- Jung SH, Lee HC, Yu DM et al (2016) Heparan sulfation is essential for the prevention of cellular senescence. Cell Death Differ 23, 417-429 https://doi.org/10.1038/cdd.2015.107
- Lee JJ, Lee JH, Ko YG, Hong SI and Lee JS (2010) Prevention of premature senescence requires JNK regulation of Bcl-2 and reactive oxygen species. Oncogene 29, 561-575 https://doi.org/10.1038/onc.2009.355
- Stambolic V, Suzuki A, de la Pompa JL et al (1998) Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN. Cell 95, 29-39 https://doi.org/10.1016/S0092-8674(00)81780-8
- Trotman LC, Niki M, Dotan ZA et al (2003) Pten dose dictates cancer progression in the prostate. PLoS Biol 1, E5 https://doi.org/10.1371/journal.pbio.0000005
- Chen Z, Trotman LC, Shaffer D et al (2005) Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis. Nature 436, 725-730 https://doi.org/10.1038/nature03918
- Lee JJ, Kim BC, Park MJ et al (2011) PTEN status switches cell fate between premature senescence and apoptosis in glioma exposed to ionizing radiation. Cell Death Differ 18, 666-677 https://doi.org/10.1038/cdd.2010.139
- Kalathur M, Toso A, Chen J et al (2015) A chemogenomic screening identifies CK2 as a target for pro-senescence therapy in PTEN-deficient tumours. Nat Commun 6, 7227 https://doi.org/10.1038/ncomms8227
- Lapenna S and Giordano A (2009) Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov 8, 547-566 https://doi.org/10.1038/nrd2907
- Campaner S, Doni M, Hydbring P et al (2010) Cdk2 suppresses cellular senescence induced by the c-myc oncogene. Nat Cell Biol 12, 54-59 https://doi.org/10.1038/ncb2004
- Puyol M, Martin A, Dubus P et al (2010) A synthetic lethal interaction between K-Ras oncogenes and Cdk4 unveils a therapeutic strategy for non-small cell lung carcinoma. Cancer Cell 18, 63-73 https://doi.org/10.1016/j.ccr.2010.05.025
- Lin HK, Chen Z, Wang G et al (2010) Skp2 targeting suppresses tumorigenesis by Arf-p53-independent cellular senescence. Nature 464, 374-379 https://doi.org/10.1038/nature08815
- Kuilman T and Peeper DS (2009) Senescence-messaging secretome: SMS-ing cellular stress. Nat Rev Cancer 9, 81-94 https://doi.org/10.1038/nrc2560
- Coppe JP, Desprez PY, Krtolica A and Campisi J (2010) The senescence-associated secretory phenotype: the dark side of tumor suppression. Annu Rev Pathol 5, 99-118 https://doi.org/10.1146/annurev-pathol-121808-102144
- Coppe JP, Kauser K, Campisi J and Beausejour CM (2006) Secretion of vascular endothelial growth factor by primary human fibroblasts at senescence. J Biol Chem 281, 29568-29574 https://doi.org/10.1074/jbc.M603307200
- Coppe JP, Patil CK, Rodier F et al (2008) Senescenceassociated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol 6, 2853-2868
- Han NK, Kim BC, Lee HC et al (2012) Secretome analysis of ionizing radiation-induced senescent cancer cells reveals that secreted RKIP plays a critical role in neighboring cell migration. Proteomics 12, 2822-2832 https://doi.org/10.1002/pmic.201100419