Ionizing Radiation-Induced Endothelial Cell Senescence and Cardiovascular Diseases

Radiation Research

Volumn 186, Issue 2, 2016, Pages 153-161

  Wang, Yingying ^a   Boerma, Marjan ^a   Zhou, Daohong ^a  

^a UNIVERSITY OF ARKANSAS FOR MEDICAL SCIENCES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CELL ADHESION MOLECULE; CYTOKINE; NITRIC OXIDE; REACTIVE OXYGEN METABOLITE; THROMBOMODULIN;

ANGIOGENESIS; APOPTOSIS; CARDIOVASCULAR DISEASE; CELL PROLIFERATION; CONFERENCE PAPER; CYTOKINE PRODUCTION; ENDOTHELIAL DYSFUNCTION; ENDOTHELIUM CELL; HEMOSTASIS; HUMAN; IN VITRO STUDY; INFLAMMATION; IONIZING RADIATION; NONHUMAN; OXIDATIVE STRESS; PRIORITY JOURNAL; PROTEIN EXPRESSION; RADIATION EXPOSURE; SENESCENCE; VASODILATATION; ANIMAL; CARDIOVASCULAR DISEASES; CELL AGING; CYTOLOGY; NEOPLASMS; PATHOLOGY; RADIATION INJURIES; RADIATION RESPONSE;

ANIMALS; CARDIOVASCULAR DISEASES; CELL AGING; ENDOTHELIAL CELLS; HUMANS; NEOPLASMS; RADIATION INJURIES;

EID: 84982242397     PISSN: 00337587     EISSN: 19385404     Source Type: Journal    
DOI: 10.1667/RR14445.1     Document Type: Conference Paper

References (108)

1. Adams MJ, Lipsitz SR, Colan SD, Tarbell NJ, Treves ST, Diller L, et al. Cardiovascular status in long-term survivors of Hodgkin's disease treated with chest radiotherapy. J Clin Oncol 2004; 22:3139-48.
2. Darby SC, McGale P, Taylor CW, Peto R. Long-term mortality from heart disease and lung cancer after radiotherapy for early breast cancer: prospective cohort study of about 300, 000 women in US SEER cancer registries. Lancet Oncol 2005; 6:557-65.
3. Early Breast Cancer Trialists Collaborative Group. Favourable and unfavourable effects on long-term survival of radiotherapy for early breast cancer: an overview of the randomised trials. Lancet 2000; 355:1757-70.
4. Heidenreich PA, Kapoor JR. Radiation induced heart disease: systemic disorders in heart disease. Heart 2009; 95:252-8.
5. Martinou M, Gaya A. Cardiac complications after radical radiotherapy. Semin Oncol 2013; 40:178-85.
6. Preston DL, Shimizu Y, Pierce DA, Suyama A, Mabuchi K. Studies of mortality of atomic bomb survivors. Report 13: Solid cancer and noncancer disease mortality: 1950-1997. Radiat Res 2003; 160:381-407.
7. McGale P, Darby SC. Low doses of ionizing radiation and circulatory diseases: a systematic review of the published epidemiological evidence. Radiat Res 2005; 163:247-57.
8. Hauptmann M, Mohan AK, Doody MM, Linet MS, Mabuchi K. Mortality from diseases of the circulatory system in radiologic technologists in the United States. Am J Epidemiol 2003; 157:239-48.
9. Ivanov VK, Maksioutov MA, Chekin SY, Petrov AV, Biryukov AP, Kruglova ZG, et al. The risk of radiation-induced cerebrovascular disease in Chernobyl emergency workers. Health Phys 2006; 90:199-207.
10. Darby SC, Ewertz M, McGale P, Bennet AM, Blom-Goldman U, Bronnum D, et al. Risk of ischemic heart disease in women after radiotherapy for breast cancer. N Engl J Med 2013; 368:987-98.
11. Kole TP, Aghayere O, Kwah J, Yorke ED, Goodman KA. Comparison of heart and coronary artery doses associated with intensity-modulated radiotherapy versus three-dimensional conformal radiotherapy for distal esophageal cancer. Int J Radiat Oncol Biol Phys 2012; 83:1580-6.
12. Tillman GF, Pawlicki T, Koong AC, Goodman KA. Preoperative versus postoperative radiotherapy for locally advanced gastroesophageal junction and proximal gastric cancers: a comparison of normal tissue radiation doses. Dis Esophagus 2008; 21:437-44.
13. Wu WC, Chan CL, Wong YW, Cuijpers JP. A study on the influence of breathing phases in intensity-modulated radiotherapy of lung tumours using four-dimensional CT. Br J Radiol 2009; 83:252-6.
14. Bergmann O, Zdunek S, Felker A, Salehpour M, Alkass K, Bernard S, et al. Dynamics of cell generation and turnover in the human heart. Cell 2015; 161:1566-75.
15. Dong X, Tong F, Qian C, Zhang R, Dong J, Wu G, et al. NEMO modulates radiation-induced endothelial senescence of human umbilical veins through NF-kappaB signal pathway. Radiat Res 2015; 183:82-93.
16. Heo JI, Kim W, Choi KJ, Bae S, Jeong JH, Kim KS. XIAPassociating factor 1, a transcriptional target of BRD7, contributes to endothelial cell senescence. Oncotarget 2016; 7:5118-30.
17. Kim KS, Kim JE, Choi KJ, Bae S, Kim DH. Characterization of DNA damage-induced cellular senescence by ionizing radiation in endothelial cells. Int J Radiat Biol 2014; 90:71-80.
18. Lowe D, Raj K. Premature aging induced by radiation exhibits pro-atherosclerotic effects mediated by epigenetic activation of CD44 expression. Aging Cell 2014; 13:900-10.
19. Mendonca MS, Chin-Sinex H, Dhaemers R, Mead LE, Yoder MC, Ingram DA. Differential mechanisms of x-ray-induced cell death in human endothelial progenitor cells isolated from cord blood and adults. Radiat Res 2011; 176:208-16.
20. Oh CW, Bump EA, Kim JS, Janigro D, Mayberg MR. Induction of a senescence-like phenotype in bovine aortic endothelial cells by ionizing radiation. Radiat Res 2001; 156:232-40.
21. Panganiban RA, Day RM. Inhibition of IGF-1R prevents ionizing radiation-induced primary endothelial cell senescence. PLoS One 2013; 8:e78589.
22. Panganiban RA, Mungunsukh O, Day RM. X-irradiation induces ER stress, apoptosis, and senescence in pulmonary artery endothelial cells. Int J Radiat Biol 2013; 89:656-67.
23. Park H, Kim CH, Jeong JH, Park M, Kim KS. GDF15 contributes to radiation-induced senescence through the ros-mediated p16 pathway in human endothelial cells. Oncotarget 2016; 7:9634-44.
24. Petrache I, Petrusca DN, Bowler RP, Kamocki K. Involvement of ceramide in cell death responses in the pulmonary circulation. Proc Am Thorac Soc 2011; 8:492-6.
25. Sermsathanasawadi N, Ishii H, Igarashi K, Miura M, Yoshida M, Inoue Y, et al. Enhanced adhesion of early endothelial progenitor cells to radiation-induced senescence-like vascular endothelial cells in vitro. J Radiat Res 2009; 50:469-75.
26. Ungvari Z, Podlutsky A, Sosnowska D, Tucsek Z, Toth P, Deak F, et al. Ionizing radiation promotes the acquisition of a senescence-associated secretory phenotype and impairs angiogenic capacity in cerebromicrovascular endothelial cells: role of increased DNA damage and decreased DNA repair capacity in microvascular radiosensitivity. J Gerontol A Biol Sci Med Sci 2013; 68:1443-57.
27. Yentrapalli R, Azimzadeh O, Sriharshan A, Malinowsky K, Merl J, Wojcik A, et al. The PI3K/Akt/mTOR pathway is implicated in the premature senescence of primary human endothelial cells exposed to chronic radiation. PLoS One 2013; 8:e70024.
28. Yentrapalli R, Azimzadeh O, Barjaktarovic Z, Sarioglu H, Wojcik A, Harms-Ringdahl M, et al. Quantitative proteomic analysis reveals induction of premature senescence in human umbilical vein endothelial cells exposed to chronic low-dose rate gamma radiation. Proteomics 2013; 13:1096-107.
29. Haimovitz-Friedman A, Kan CC, Ehleiter D, Persaud RS, McLoughlin M, Fuks Z, et al. Ionizing radiation acts on cellular membranes to generate ceramide and initiate apoptosis. J Exp Med 1994; 180:525-35.
30. Lee CL, Moding EJ, Cuneo KC, Li Y, Sullivan JM, Mao L, et al. p53 functions in endothelial cells to prevent radiation-induced myocardial injury in mice. Sci Signal 2012; 5:ra52.
31. Garcia-Barros M, Paris F, Cordon-Cardo C, Lyden D, Rafii S, Haimovitz-Friedman A, et al. Tumor response to radiotherapy regulated by endothelial cell apoptosis. Science 2003; 300:1155-9.
32. Paris F, Fuks Z, Kang A, Capodieci P, Juan G, Ehleiter D, et al. Endothelial apoptosis as the primary lesion initiating intestinal radiation damage in mice. Science 2001; 293:293-7.
33. Pena LA, Fuks Z, Kolesnick RN. Radiation-induced apoptosis of endothelial cells in the murine central nervous system: protection by fibroblast growth factor and sphingomyelinase deficiency. Cancer Res 2000; 60:321-7.
34. Kirsch DG, Santiago PM, di TE, Sullivan JM, Hou WS, Dayton T, et al. p53 controls radiation-induced gastrointestinal syndrome in mice independent of apoptosis. Science 2010; 327:593-6.
35. Hooper AT, Butler JM, Nolan DJ, Kranz A, Iida K, Kobayashi M, et al. Engraftment and reconstitution of hematopoiesis is dependent on VEGFR2-mediated regeneration of sinusoidal endothelial cells. Cell Stem Cell 2009; 4:263-74.
36. Doan PL, Russell JL, Himburg HA, Helms K, Harris JR, Lucas J, et al. Tie2() bone marrow endothelial cells regulate hematopoietic stem cell regeneration following radiation injury. Stem Cells 2013; 31:327-37.
37. Muramoto GG, Chen B, Cui X, Chao NJ, Chute JP. Vascular endothelial cells produce soluble factors that mediate the recovery of human hematopoietic stem cells after radiation injury. Biol Blood Marrow Transplant 2006; 12:530-40.
38. Campisi J. Aging, cellular senescence, and cancer. Annu Rev Physiol 2013; 75:685-705.
39. Childs BG, Durik M, Baker DJ, van Deursen JM. Cellular senescence in aging and age-related disease: from mechanisms to therapy. Nat Med 2015; 21:1424-35.
40. Kim G, Meriin AB, Gabai VL, Christians E, Benjamin I, Wilson A, et al. The heat shock transcription factor Hsf1 is downregulated in DNA damage-associated senescence, contributing to the maintenance of senescence phenotype. Aging Cell 2012; 11:617-27.
41. Yaglom JA, McFarland C, Mirny L, Sherman MY. Oncogenetriggered suppression of DNA repair leads to DNA instability in cancer. Oncotarget 2014; 5:8367-78.
42. Hoenicke L, Zender L. Immune surveillance of senescent cells-biological significance in cancer-and non-cancer pathologies. Carcinogenesis 2012; 33:1123-6.
43. Kang TW, Yevsa T, Woller N, Hoenicke L, Wuestefeld T, Dauch D, et al. Senescence surveillance of pre-malignant hepatocytes limits liver cancer development. Nature 2011; 479:547-51.
44. Krizhanovsky V, Yon M, Dickins RA, Hearn S, Simon J, Miething C, et al. Senescence of activated stellate cells limits liver fibrosis. Cell 2008; 134:657-67.
45. Acosta JC, Gil J. Senescence: a new weapon for cancer therapy. Trends Cell Biol 2012; 22:211-9.
46. Citrin DE, Shankavaram U, Horton JA, Shield W, III, Zhao S, Asano H, et al. Role of type II pneumocyte senescence in radiation-induced lung fibrosis. J Natl Cancer Inst 2013; 105:1474-84.
47. Suzuki M, Boothman DA. Stress-induced premature senescence (SIPS)-influence of SIPS on radiotherapy. J Radiat Res 2008; 49:105-12.
48. Chang J, Wang Y, Shao L, Laberge RM, Demaria M, Campisi J, et al. Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice. Nat Med 2016; 22:78-83.
49. Ohtani N, Takahashi A, Mann DJ, Hara E. Cellular senescence: a double-edged sword in the fight against cancer. Exp Dermatol 2012; 21 Suppl 1:1-4.
50. Luo X, Suzuki M, Ghandhi SA, Amundson SA, Boothman DA. ATM regulates insulin-like growth factor 1-secretory clusterin (IGF-1-sCLU) expression that protects cells against senescence. PLoS One 2014; 9:e99983.
51. Bondar T, Medzhitov R. p53-mediated hematopoietic stem and progenitor cell competition. Cell Stem Cell 2010; 6:309-22.
52. Marusyk A, Casas-Selves M, Henry CJ, Zaberezhnyy V, Klawitter J, Christians U, et al. Irradiation alters selection for oncogenic mutations in hematopoietic progenitors. Cancer Res 2009; 69:7262-9.
53. Marusyk A, Porter CC, Zaberezhnyy V, DeGregori J. Irradiation selects for p53-deficient hematopoietic progenitors. PLoS Biol 2010; 8:e1000324.
54. Shao L, Feng W, Li H, Gardner D, Luo Y, Wang Y, et al. Total body irradiation causes long-term mouse BM injury via induction of HSC premature senescence in an Ink4a-and Arf-independent manner. Blood 2014; 123:3105-15.
55. Wang Y, Schulte BA, LaRue AC, Ogawa M, Zhou D. Total body irradiation selectively induces murine hematopoietic stem cell senescence. Blood 2006; 107:358-66.
56. Baker DJ, Childs BG, Durik M, Wijers ME, Sieben CJ, Zhong J, et al. Naturally occurring p16Ink4a-positive cells shorten heathy lifespan. Nature 2016; 530:184-9.
57. Azimzadeh O, Sievert W, Sarioglu H, Merl-Pham J, Yentrapalli R, Bakshi MV, et al. Integrative proteomics and targeted transcriptomics analyses in cardiac endothelial cells unravel mechanisms of long-term radiation-induced vascular dysfunction. J Proteome Res 2015; 14:1203-19.
58. Robles SJ, Adami GR. Agents that cause DNA double strand breaks lead to p16INK4a enrichment and the premature senescence of normal fibroblasts. Oncogene 1998; 16:1113-23.
59. te Poele RH, Okorokov AL, Jardine L, Cummings J, Joel SP. DNA damage is able to induce senescence in tumor cells in vitro and in vivo. Cancer Res 2002; 62:1876-83.
60. Campisi J. Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors. Cell 2005; 120:513-22.
61. Beausejour CM, Krtolica A, Galimi F, Narita M, Lowe SW, Yaswen P, et al. Reversal of human cellular senescence: roles of the p53 and p16 pathways. EMBO J 2003; 22:4212-22.
62. Chen J, Huang X, Halicka D, Brodsky S, Avram A, Eskander J, et al. Contribution of p16INK4a and p21CIP1 pathways to induction of premature senescence of human endothelial cells: permissive role of p53. Am J Physiol Heart Circ Physiol 2006; 290:H1575-86.
63. Cho JH, Kim MJ, Kim KJ, Kim JR. POZ/BTB and AT-hookcontaining zinc finger protein 1 (PATZ1) inhibits endothelial cell senescence through a p53 dependent pathway. Cell Death Differ 2012; 19:703-12.
64. Kim HJ, Cho JH, Kim JR. Downregulation of Polo-like kinase 1 induces cellular senescence in human primary cells through a p53-dependent pathway. J Gerontol A Biol Sci Med Sci 2013; 68:1145-56.
65. Igarashi K, Miura M. Inhibition of a radiation-induced senescence-like phenotype: a possible mechanism for potentially lethal damage repair in vascular endothelial cells. Radiat Res 2008; 170:534-9.
66. Paneni F, Osto E, Costantino S, Mateescu B, Briand S, Coppolino G, et al. Deletion of the activated protein-1 transcription factor JunD induces oxidative stress and accelerates age-related endothelial dysfunction. Circulation 2013; 127:1229-21.
67. Zhan H, Suzuki T, Aizawa K, Miyagawa K, Nagai R. Ataxia telangiectasia mutated (ATM)-mediated DNA damage response in oxidative stress-induced vascular endothelial cell senescence. J Biol Chem 2010; 285:29662-70.
68. Zhang E, Guo Q, Gao H, Xu R, Teng S, Wu Y. Metformin and resveratrol inhibited high glucose-induced metabolic memory of endothelial senescence through SIRT1/p300/p53/p21 Pathway. PLoS One 2015; 10:e0143814.
69. Wan YZ, Gao P, Zhou S, Zhang ZQ, Hao DL, Lian LS, et al. SIRT1-mediated epigenetic downregulation of plasminogen activator inhibitor-1 prevents vascular endothelial replicative senescence. Aging Cell 2014; 13:890-9.
70. Imaizumi N, Monnier Y, Hegi M, Mirimanoff RO, Ruegg C. Radiotherapy suppresses angiogenesis in mice through TGFbetaRI/ ALK5-dependent inhibition of endothelial cell sprouting. PLoS One 2010; 5:e11084.
71. Chang H, Rha SY, Jeung HC, Park KH, Kim TS, Kim YB, et al. Telomerase-and angiogenesis-related gene responses to irradiation in human umbilical vein endothelial cells. Int J Mol Med 2013; 31:1202-8.
72. Spallarossa P, Altieri P, Barisione C, Passalacqua M, Aloi C, Fugazza G, et al. p38 MAPK and JNK antagonistically control senescence and cytoplasmic p16INK4A expression in doxorubicin-treated endothelial progenitor cells. PLoS One 2010; 5:e15583.
73. Iwasa H, Han J, Ishikawa F. Mitogen-activated protein kinase p38 defines the common senescence-signalling pathway. Genes Cells 2003; 8:131-44.
74. Wang Y, Kellner J, Liu L, Zhou D. Inhibition of p38 mitogenactivated protein kinase promotes ex vivo hematopoietic stem cell expansion. Stem Cells Dev 2011; 20:1143-52.
75. Koziel R, Pircher H, Kratochwil M, Lener B, Hermann M, Dencher NA, et al. Mitochondrial respiratory chain complex I is inactivated by NADPH oxidase Nox4. Biochem J 2013; 452:231-9.
76. Frey RS, Ushio-Fukai M, Malik AB. NADPH oxidase-dependent signaling in endothelial cells: role in physiology and pathophysiology. Antioxid Redox Signal 2009; 11:791-810.
77. Donato AJ, Morgan RG, Walker AE, Lesniewski LA. Cellular and molecular biology of aging endothelial cells. J Mol Cell Cardiol 2015; 89:122-35.
78. Muller M. Cellular senescence: molecular mechanisms, in vivo significance, and redox considerations. Antioxid Redox Signal 2009; 11:59-98.
79. Coppe JP, Desprez PY, Krtolica A, Campisi J. The senescenceassociated secretory phenotype: the dark side of tumor suppression. Annu Rev Pathol 2010; 5:99-118.
80. Geiger H, Pawar SA, Kerschen EJ, Nattamai KJ, Hernandez I, Liang HP, et al. Pharmacological targeting of the thrombomodulin-activated protein C pathway mitigates radiation toxicity. Nat Med 2012; 18:1123-9.
81. Pathak R, Shao L, Ghosh SP, Zhou D, Boerma M, Weiler H, et al. Thrombomodulin contributes to gamma tocotrienol-mediated lethality protection and hematopoietic cell recovery in irradiated mice. PLoS One 2015; 10:e0122511.
82. Erusalimsky JD. Vascular endothelial senescence: from mechanisms to pathophysiology. J Appl Physiol (1985) 2009; 106:326-32.
83. Abderrahmani R, Francois A, Buard V, Tarlet G, Blirando K, Hneino M, et al. PAI-1-dependent endothelial cell death determines severity of radiation-induced intestinal injury. PLoS One 2012; 7:e35740.
84. Tian XL, Li Y. Endothelial cell senescence and age-related vascular diseases. J Genet Genomics 2014; 41:485-95.
85. Minamino T, Miyauchi H, Yoshida T, Tateno K, Kunieda T, Komuro I. Vascular cell senescence and vascular aging. J Mol Cell Cardiol 2004; 36:175-83.
86. Minamino T, Komuro I. Vascular cell senescence: contribution to atherosclerosis. Circ Res 2007; 100:15-26.
87. Kovacic JC, Moreno P, Nabel EG, Hachinski V, Fuster V. Cellular senescence, vascular disease, and aging: part 2 of a 2-part review: clinical vascular disease in the elderly. Circulation 2011; 123:1900-10.
88. Kovacic JC, Moreno P, Hachinski V, Nabel EG, Fuster V. Cellular senescence, vascular disease, and aging: Part 1 of a 2-part review. Circulation 2011; 123:1650-60.
89. Korpela E, Liu SK. Endothelial perturbations and therapeutic strategies in normal tissue radiation damage. Radiat Oncol 2014; 9:266-73.
90. Taunk NK, Haffty BG, Kostis JB, Goyal S. Radiation-induced heart disease: pathologic abnormalities and putative mechanisms. Front Oncol 2015; 5:39-46.
91. Zagar TM, Cardinale DM, Marks LB. Breast cancer therapyassociated cardiovascular disease. Nat Rev Clin Oncol 2016; 13:172-84.
92. Stewart FA, Heeneman S, Te PJ, Kruse J, Russell NS, Gijbels M, et al. Ionizing radiation accelerates the development of atherosclerotic lesions in ApoE-/-mice and predisposes to an inflammatory plaque phenotype prone to hemorrhage. Am J Pathol 2006; 168:649-58.
93. Yeung TK, Lauk S, Simmonds RH, Hopewell JW, Trott KR. Morphological and functional changes in the rat heart after X irradiation: strain differences. Radiat Res 1989; 119:489-99.
94. Baker JE, Fish BL, Su J, Haworth ST, Strande JL, Komorowski RA, et al. 10 Gy total body irradiation increases risk of coronary sclerosis, degeneration of heart structure and function in a rat model. Int J Radiat Biol 2009; 85:1089-100.
95. Higashi Y, Kihara Y, Noma K. Endothelial dysfunction and hypertension in aging. Hypertens Res 2012; 35:1039-47.
96. Tchkonia T, Zhu Y, van DJ, Campisi J, Kirkland JL. Cellular senescence and the senescent secretory phenotype: therapeutic opportunities. J Clin Invest 2013; 123:966-72.
97. Herranz N, Gallage S, Mellone M, Wuestefeld T, Klotz S, Hanley CJ, et al. mTOR regulates MAPKAPK2 translation to control the senescence-associated secretory phenotype. Nat Cell Biol 2015; 17:1205-17.
98. Laberge RM, Sun Y, Orjalo AV, Patil CK, Freund A, Zhou L, et al. MTOR regulates the pro-tumorigenic senescence-associated secretory phenotype by promoting IL1A translation. Nat Cell Biol 2015; 17:1049-61.
99. Wu Z, Yu Y, Liu C, Xiong Y, Montani JP, Yang Z, et al. Role of p38 mitogen-activated protein kinase in vascular endothelial aging: interaction with Arginase-II and S6K1 signaling pathway. Aging (Albany NY) 2015; 7:70-81.
100. Chien Y, Scuoppo C, Wang X, Fang X, Balgley B, Bolden JE, et al. Control of the senescence-associated secretory phenotype by NF-kappaB promotes senescence and enhances chemosensitivity. Genes Dev 2011; 25:2125-36.
101. Freund A, Patil CK, Campisi J. p38MAPK is a novel DNA damage response-independent regulator of the senescenceassociated secretory phenotype. EMBO J 2011; 30:1536-48.
102. Xu M, Tchkonia T, Ding H, Ogrodnik M, Lubbers ER, Pirtskhalava T, et al. JAK inhibition alleviates the cellular senescence-associated secretory phenotype and frailty in old age. Proc Natl Acad Sci U S A 2015; 112:E6301-10.
103. Baker DJ, Wijshake T, Tchkonia T, LeBrasseur NK, Childs BG, van de Sluis B, et al. Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature 2011; 479:232-6.
104. Zhu Y, Tchkonia T, Pirtskhalava T, Gower AC, Ding H, Giorgadze N, et al. The Achilles' heel of senescent cells: from transcriptome to senolytic drugs. Aging Cell 2015; 14:644-58.
105. Childs BG, Baker DJ, Kirkland JL, Campisi J, van Deursen JM. Senescence and apoptosis: dueling or complementary cell fates? EMBO Rep 2014; 15:1139-53.
106. Tse C, Shoemaker AR, Adickes J, Anderson MG, Chen J, Jin S, et al. ABT-263: a potent and orally bioavailable Bcl-2 family inhibitor. Cancer Res 2008; 68:3421-8.
107. Munoz-Espin D, Serrano M. Cellular senescence: from physiology to pathology. Nat Rev Mol Cell Biol 2014; 15:482-96.
108. van Deursen JM. The role of senescent cells in ageing. Nature 2014; 509:439-46.