1. Baker DJ, Wijshake T, Tchkonia T, LeBrasseur NK, Childs BG, van de Sluis B, Kirkland JL, van Deursen JM. Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature. 2011; 479:232–36. https://doi.org/10.1038/nature10600 PMID:22048312
2. Childs BG, Gluscevic M, Baker DJ, Laberge RM, Marquess D, Dananberg J, van Deursen JM. Senescent cells: an emerging target for diseases of ageing. Nat Rev Drug Discov. 2017; 16:718–35. https://doi.org/10.1038/nrd.2017.116 PMID:28729727
3. Gorgoulis V, Adams PD, Alimonti A, Bennett DC, Bischof O, Bishop C, Campisi J, Collado M, Evangelou K, Ferbeyre G, Gil J, Hara E, Krizhanovsky V, et al. Cellular Senescence: Defining a Path Forward. Cell. 2019; 179:813–27. https://doi.org/10.1016/j.cell.2019.10.005 PMID:31675495
4. Coppé JP, Patil CK, Rodier F, Sun Y, Muñoz DP, Goldstein J, Nelson PS, Desprez PY, Campisi J. Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol. 2008; 6:2853–68. https://doi.org/10.1371/journal.pbio.0060301 PMID:19053174
5. Demaria M, Ohtani N, Youssef SA, Rodier F, Toussaint W, Mitchell JR, Laberge RM, Vijg J, Van Steeg H, Dollé ME, Hoeijmakers JH, de Bruin A, Hara E, Campisi J. An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA. Dev Cell. 2014; 31:722–33. https://doi.org/10.1016/j.devcel.2014.11.012 PMID:25499914
6. Faget DV, Ren Q, Stewart SA. Unmasking senescence: context-dependent effects of SASP in cancer. Nat Rev Cancer. 2019; 19:439–53. https://doi.org/10.1038/s41568-019-0156-2 PMID:31235879
7. Ito Y, Hoare M, Narita M. Spatial and Temporal Control of Senescence. Trends Cell Biol. 2017; 27:820–32. https://doi.org/10.1016/j.tcb.2017.07.004 PMID:28822679
8. Basisty N, Kale A, Jeon OH, Kuehnemann C, Payne T, Rao C, Holtz A, Shah S, Sharma V, Ferrucci L, Campisi J, Schilling B. A proteomic atlas of senescence-associated secretomes for aging biomarker development. PLoS Biol. 2020; 18:e3000599. https://doi.org/10.1371/journal.pbio.3000599 PMID:31945054
9. d’Adda di Fagagna F, Reaper PM, Clay-Farrace L, Fiegler H, Carr P, Von Zglinicki T, Saretzki G, Carter NP, Jackson SP. A DNA damage checkpoint response in telomere-initiated senescence. Nature. 2003; 426:194–98. https://doi.org/10.1038/nature02118 PMID:14608368
10. Rodier F, Muñoz DP, Teachenor R, Chu V, Le O, Bhaumik D, Coppé JP, Campeau E, Beauséjour CM, Kim SH, Davalos AR, Campisi J. DNA-SCARS: distinct nuclear structures that sustain damage-induced senescence growth arrest and inflammatory cytokine secretion. J Cell Sci. 2011; 124:68–81. https://doi.org/10.1242/jcs.071340 PMID:21118958
11. Malaquin N, Martinez A, Rodier F. Keeping the senescence secretome under control: Molecular reins on the senescence-associated secretory phenotype. Exp Gerontol. 2016; 82:39–49. https://doi.org/10.1016/j.exger.2016.05.010 PMID:27235851
12. Casella G, Munk R, Kim KM, Piao Y, De S, Abdelmohsen K, Gorospe M. Transcriptome signature of cellular senescence. Nucleic Acids Res. 2019; 47:11476. https://doi.org/10.1093/nar/gkz879 PMID:31612919
13. Place RF, Noonan EJ, Giardina C. HDACs and the senescent phenotype of WI-38 cells. BMC Cell Biol. 2005; 6:37. https://doi.org/10.1186/1471-2121-6-37 PMID:16250917
15. Malaquin N, Olivier MA, Martinez A, Nadeau S, Sawchyn C, Coppé JP, Cardin G, Mallette FA, Campisi J, Rodier F. Non-canonical ATM/MRN activities temporally define the senescence secretory program. EMBO Rep. 2020; 21:e50718. https://doi.org/10.15252/embr.202050718 PMID:32785991
16. Pospelova TV, Demidenko ZN, Bukreeva EI, Pospelov VA, Gudkov AV, Blagosklonny MV. Pseudo-DNA damage response in senescent cells. Cell Cycle. 2009; 8:4112–18. https://doi.org/10.4161/cc8.24.10215 PMID:19946210
17. Han X, Niu J, Zhao Y, Kong Q, Tong T, Han L. HDAC4 stabilizes SIRT1 via sumoylation SIRT1 to delay cellular senescence. Clin Exp Pharmacol Physiol. 2016; 43:41–46. https://doi.org/10.1111/1440-1681.12496 PMID:26414199
18. Eckschlager T, Plch J, Stiborova M, Hrabeta J. Histone Deacetylase Inhibitors as Anticancer Drugs. Int J Mol Sci. 2017; 18:1414. https://doi.org/10.3390/ijms18071414 PMID:28671573
19. Di Bernardo G, Squillaro T, Dell’Aversana C, Miceli M, Cipollaro M, Cascino A, Altucci L, Galderisi U. Histone deacetylase inhibitors promote apoptosis and senescence in human mesenchymal stem cells. Stem Cells Dev. 2009; 18:573–81. https://doi.org/10.1089/scd.2008.0172 PMID:18694296
20. Sobecki M, Mrouj K, Camasses A, Parisis N, Nicolas E, Llères D, Gerbe F, Prieto S, Krasinska L, David A, Eguren M, Birling MC, Urbach S, et al. The cell proliferation antigen Ki-67 organises heterochromatin. Elife. 2016; 5:e13722. https://doi.org/10.7554/eLife.13722 PMID:26949251
21. Freese K, Seitz T, Dietrich P, Lee SM, Thasler WE, Bosserhoff A, Hellerbrand C. Histone Deacetylase Expressions in Hepatocellular Carcinoma and Functional Effects of Histone Deacetylase Inhibitors on Liver Cancer Cells In Vitro. Cancers (Basel). 2019; 11:1587. https://doi.org/10.3390/cancers11101587 PMID:31635225
22. Freund A, Laberge RM, Demaria M, Campisi J. Lamin B1 loss is a senescence-associated biomarker. Mol Biol Cell. 2012; 23:2066–75. https://doi.org/10.1091/mbc.E11-10-0884 PMID:22496421
23. Harms KL, Chen X. Histone deacetylase 2 modulates p53 transcriptional activities through regulation of p53-DNA binding activity. Cancer Res. 2007; 67: 3145–52. https://doi.org/10.1158/0008-5472.CAN-06-4397 PMID:17409421
25. Freund A, Orjalo AV, Desprez PY, Campisi J. Inflammatory networks during cellular senescence: causes and consequences. Trends Mol Med. 2010; 16:238–46. https://doi.org/10.1016/j.molmed.2010.03.003 PMID:20444648
26. Lorenz V, Hessenkemper W, Rödiger J, Kyrylenko S, Kraft F, Baniahmad A. Sodium butyrate induces cellular senescence in neuroblastoma and prostate cancer cells. Horm Mol Biol Clin Investig. 2011; 7:265–72. https://doi.org/10.1515/HMBCI.2011.020 PMID:25961265
27. Gonzalez LC, Ghadaouia S, Martinez A, Rodier F. Premature aging/senescence in cancer cells facing therapy: good or bad? Biogerontology. 2016; 17:71–87. https://doi.org/10.1007/s10522-015-9593-9 PMID:26330289
28. Groh T, Hrabeta J, Khalil MA, Doktorova H, Eckschlager T, Stiborova M. The synergistic effects of DNA-damaging drugs cisplatin and etoposide with a histone deacetylase inhibitor valproate in high-risk neuroblastoma cells. Int J Oncol. 2015; 47:343–52. https://doi.org/10.3892/ijo.2015.2996 PMID:25963435
29. Luchenko VL, Salcido CD, Zhang Y, Agama K, Komlodi-Pasztor E, Murphy RF, Giaccone G, Pommier Y, Bates SE, Varticovski L. Schedule-dependent synergy of histone deacetylase inhibitors with DNA damaging agents in small cell lung cancer. Cell Cycle. 2011; 10:3119–28. https://doi.org/10.4161/cc.10.18.17190 PMID:21900747
30. Ryu CH, Yoon WS, Park KY, Kim SM, Lim JY, Woo JS, Jeong CH, Hou Y, Jeun SS. Valproic acid downregulates the expression of MGMT and sensitizes temozolomide-resistant glioma cells. J Biomed Biotechnol. 2012; 2012:987495. https://doi.org/10.1155/2012/987495 PMID:22701311
31. Pazolli E, Alspach E, Milczarek A, Prior J, Piwnica-Worms D, Stewart SA. Chromatin remodeling underlies the senescence-associated secretory phenotype of tumor stromal fibroblasts that supports cancer progression. Cancer Res. 2012; 72:2251–61. https://doi.org/10.1158/0008-5472.CAN-11-3386 PMID:22422937
32. Zhang HS, Gavin M, Dahiya A, Postigo AA, Ma D, Luo RX, Harbour JW, Dean DC. 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. 2000; 101:79–89. https://doi.org/10.1016/S0092-8674(00)80625-X PMID:10778858
33. Siddiqui H, Solomon DA, Gunawardena RW, Wang Y, Knudsen ES. Histone deacetylation of RB-responsive promoters: requisite for specific gene repression but dispensable for cell cycle inhibition. Mol Cell Biol. 2003; 23:7719–31. https://doi.org/10.1128/MCB.23.21.7719-7731.2003 PMID:14560017
34. Zhou H, Cai Y, Liu D, Li M, Sha Y, Zhang W, Wang K, Gong J, Tang N, Huang A, Xia J. Pharmacological or transcriptional inhibition of both HDAC1 and 2 leads to cell cycle blockage and apoptosis via p21Waf1/Cip1 and p19INK4d upregulation in hepatocellular carcinoma. Cell Prolif. 2018; 51:e12447. https://doi.org/10.1111/cpr.12447 PMID:29484736
35. Clarke JD, Hsu A, Yu Z, Dashwood RH, Ho E. Differential effects of sulforaphane on histone deacetylases, cell cycle arrest and apoptosis in normal prostate cells versus hyperplastic and cancerous prostate cells. Mol Nutr Food Res. 2011; 55:999–1009. https://doi.org/10.1002/mnfr.201000547 PMID:21374800
36. Zhou R, Han L, Li G, Tong T. Senescence delay and repression of p16INK4a by Lsh via recruitment of histone deacetylases in human diploid fibroblasts. Nucleic Acids Res. 2009; 37:5183–96. https://doi.org/10.1093/nar/gkp533 PMID:19561196
37. Feng Y, Wang X, Xu L, Pan H, Zhu S, Liang Q, Huang B, Lu J. The transcription factor ZBP-89 suppresses p16 expression through a histone modification mechanism to affect cell senescence. FEBS J. 2009; 276:4197–206. https://doi.org/10.1111/j.1742-4658.2009.07128.x PMID:19583777
38. Hitomi T, Matsuzaki Y, Yokota T, Takaoka Y, Sakai T. p15(INK4b) in HDAC inhibitor-induced growth arrest. FEBS Lett. 2003; 554:347–50. https://doi.org/10.1016/s0014-5793(03)01186-4 PMID:14623092
39. Elknerova K, Myslivcova D, Lacinova Z, Marinov I, Uherkova L, Stöckbauer P. Epigenetic modulation of gene expression of human leukemia cell lines - induction of cell death and senescence. Neoplasma. 2011; 58:35–44. https://doi.org/10.4149/neo 2011 01 35 PMID:21067264
40. Ghayad SE, Rammal G, Sarkis O, Basma H, Ghamloush F, Fahs A, Karam M, Harajli M, Rabeh W, Mouawad JE, Zalzali H, Saab R. The histone deacetylase inhibitor Suberoylanilide Hydroxamic Acid (SAHA) as a therapeutic agent in rhabdomyosarcoma. Cancer Biol Ther. 2019; 20:272–83. https://doi.org/10.1080/15384047.2018.1529093 PMID:30307360
41. Xu WS, Perez G, Ngo L, Gui CY, Marks PA. Induction of polyploidy by histone deacetylase inhibitor: a pathway for antitumor effects. Cancer Res. 2005; 65:7832–39. https://doi.org/10.1158/0008-5472.CAN-04-4608 PMID:16140952
42. Munro J, Barr NI, Ireland H, Morrison V, Parkinson EK. Histone deacetylase inhibitors induce a senescencelike state in human cells by a p16-dependent mechanism that is independent of a mitotic clock. Exp Cell Res. 2004; 295:525–38. https://doi.org/10.1016/j.yexcr.2004.01.017 PMID:15093749
43. Adam S, Polo SE. Blurring the line between the DNA damage response and transcription: the importance of chromatin dynamics. Exp Cell Res. 2014; 329:148–53. https://doi.org/10.1016/j.yexcr.2014.07.017 PMID:25062983
44. Hodge G, Jersmann H, Tran HB, Roscioli E, Holmes M, Reynolds PN, Hodge S. Lymphocyte senescence in COPD is associated with decreased histone deacetylase 2 expression by pro-inflammatory lymphocytes. Respir Res. 2015; 16:130. https://doi.org/10.1186/s12931-015-0287-2 PMID:26498345
45. Capece D, Verzella D, Tessitore A, Alesse E, Capalbo C, Zazzeroni F. Cancer secretome and inflammation: The bright and the dark sides of NF-κB. Semin Cell Dev Biol. 2018; 78:51–61. https://doi.org/10.1016/j.semcdb.2017.08.004 PMID:28779979
46. Shirato K, Koda T, Takanari J, Sakurai T, Ogasawara J, Imaizumi K, Ohno H, Kizaki T. Anti-Inflammatory Effect of ETAS®50 by Inhibiting Nuclear Factor- κ B p65 Nuclear Import in Ultraviolet-B-Irradiated Normal Human Dermal Fibroblasts. Evid Based Complement Alternat Med. 2018; 2018:5072986. https://doi.org/10.1155/2018/5072986 PMID:29967648
47. Waldera Lupa DM, Kalfalah F, Safferling K, Boukamp P, Poschmann G, Volpi E, Götz-Rösch C, Bernerd F, Haag L, Huebenthal U, Fritsche E, Boege F, Grabe N, et al. Characterization of Skin Aging-Associated Secreted Proteins (SAASP) Produced by Dermal Fibroblasts Isolated from Intrinsically Aged Human Skin. J Invest Dermatol. 2015; 135:1954–68. https://doi.org/10.1038/jid.2015.120 PMID:25815425
48. Debacq-Chainiaux F, Erusalimsky JD, Campisi J, Toussaint O. Protocols to detect senescence-associated beta-galactosidase (SA-betagal) activity, a biomarker of senescent cells in culture and in vivo. Nat Protoc. 2009; 4:1798–806. https://doi.org/10.1038/nprot.2009.191 PMID:20010931
49. Dimri GP, Lee X, Basile G, Acosta M, Scott G, Roskelley C, Medrano EE, Linskens M, Rubelj I, Pereira-Smith O. A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci USA. 1995; 92:9363–67. https://doi.org/10.1073/pnas.92.20.9363 PMID:7568133
50. Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc. 2008; 3:1101–08. https://doi.org/10.1038/nprot.2008.73 PMID:18546601
