DOI QR코드

DOI QR Code

Erratum to: From cell senescence to age-related diseases: differential mechanisms of action of senescence-associated secretory phenotypes

  • Byun, Hae-Ok (Department of Biochemistry, Ajou University School of Medicine) ;
  • Lee, Young-Kyoung (Department of Biochemistry, Ajou University School of Medicine) ;
  • Kim, Jeong-Min (Department of Biochemistry, Ajou University School of Medicine) ;
  • Yoon, Gyesoon (Department of Biochemistry, Ajou University School of Medicine)
  • Received : 2015.06.23
  • Published : 2016.11.30

Abstract

Cellular senescence is a process by which cells enter a state of permanent cell cycle arrest. It is commonly believed to underlie organismal aging and age-associated diseases. However, the mechanism by which cellular senescence contributes to aging and age-associated pathologies remains unclear. Recent studies showed that senescent cells exert detrimental effects on the tissue microenvironment, generating pathological facilitators or aggravators. The most significant environmental effector resulting from senescent cells is the senescence-associated secretory phenotype (SASP), which is constituted by a strikingly increased expression and secretion of diverse pro-inflammatory cytokines. Careful investigation into the components of SASPs and their mechanism of action, may improve our understanding of the pathological backgrounds of age-associated diseases. In this review, we focus on the differential expression of SASP-related genes, in addition to SASP components, during the progress of senescence. We also provide a perspective on the possible action mechanisms of SASP components, and potential contributions of SASP-expressing senescent cells, to age-associated pathologies.

Keywords

References

  1. Campisi J (2005) Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors. Cell 120, 513-522 https://doi.org/10.1016/j.cell.2005.02.003
  2. Dimri GP, Lee X, Basile G et al (1995) A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci U S A 92, 9363-9367 https://doi.org/10.1073/pnas.92.20.9363
  3. Hayflick L and Moorhead PS (1961) The serial cultivation of human diploid cell strains. Exp Cell Res 25, 585-621 https://doi.org/10.1016/0014-4827(61)90192-6
  4. Martin JA and Buckwalter JA (2001) Roles of articular cartilage aging and chondrocyte senescence in the pathogenesis of osteoarthritis. Iowa Orthop J 21, 1-7
  5. Minamino T, Miyauchi H, Yoshida T, Ishida Y, Yoshida H and Komuro I (2002) Endothelial cell senescence in human atherosclerosis: role of telomere in endothelial dysfunction. Circulation 105, 1541-1544 https://doi.org/10.1161/01.CIR.0000013836.85741.17
  6. Youdim MB and Riederer P (1993) The role of iron in senescence of dopaminergic neurons in Parkinson's disease. J Neural Transm Suppl 40, 57-67
  7. Castro P, Xia C, Gomez L, Lamb DJ and Ittmann M (2004) Interleukin-8 expression is increased in senescent prostatic epithelial cells and promotes the development of benign prostatic hyperplasia. Prostate 60, 153-159 https://doi.org/10.1002/pros.20051
  8. Baker DJ, Wijshake T, Tchkonia T et al (2011) Clearance of p16Ink4a-positive senescent cells delays age-ing-associated disorders. Nature 479, 232-236 https://doi.org/10.1038/nature10600
  9. Aikata H, Takaishi H, Kawakami Y et al (2000) Telomere reduction in human liver tissues with age and chronic inflammation. Exp Cell Res 256, 578-582 https://doi.org/10.1006/excr.2000.4862
  10. Herbig U, Jobling WA, Chen BP, Chen DJ and Sedivy JM (2004) Telomere shortening triggers senescence of human cells through a pathway involving ATM, p53, and p21(CIP1), but not p16(INK4a). Mol Cell 14, 501-513 https://doi.org/10.1016/S1097-2765(04)00256-4
  11. d'Adda di Fagagna F, Reaper PM, Clay-Farrace L et al (2003) A DNA damage checkpoint response in telo-mere-initiated senescence. Nature 426, 194-198 https://doi.org/10.1038/nature02118
  12. Rodier F, Coppe JP, Patil CK et al (2009) Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion. Nat Cell Biol 11, 973-979 https://doi.org/10.1038/ncb1909
  13. Braig M and Schmitt CA (2006) Oncogene-induced senescence: putting the brakes on tumor development. Cancer Res 66, 2881-2884 https://doi.org/10.1158/0008-5472.CAN-05-4006
  14. Lee S, Dorken B and Schmitt CA (2004) Extracorporeal photopheresis in graft-versus-host disease: ultraviolet radiation mediates T cell senescence in vivo. Transplantation 78, 484-485
  15. 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
  16. Chen QM, Tu VC, Catania J, Burton M, Toussaint O and Dilley T (2000) Involvement of Rb family proteins, focal adhesion proteins and protein synthesis in senescent mor-phogenesis induced by hydrogen peroxide. J Cell Sci 113 (Pt 22), 4087-4097
  17. Balaban RS, Nemoto S and Finkel T (2005) Mitochondria, oxidants, and aging. Cell 120, 483-495 https://doi.org/10.1016/j.cell.2005.02.001
  18. Passos JF, Nelson G, Wang C et al (2010) Feedback be-tween p21 and reactive oxygen production is necessary for cell senescence. Mol Syst Biol 6, 347
  19. Itahana K, Campisi J and Dimri GP (2007) Methods to detect biomarkers of cellular senescence: the sen-escence-associated beta-galactosidase assay. Methods Mol Biol 371, 21-31 https://doi.org/10.1007/978-1-59745-361-5_3
  20. Kuilman T, Michaloglou C, Mooi WJ and Peeper DS (2010) The essence of senescence. Genes Dev 24, 2463-2479 https://doi.org/10.1101/gad.1971610
  21. Narita M, Nunez S, Heard E et al (2003) Rb-mediated het-erochromatin formation and silencing of E2F target genes during cellular senescence. Cell 113, 703-716 https://doi.org/10.1016/S0092-8674(03)00401-X
  22. Freund A, Orjalo AV, Desprez PY and Campisi J (2010) Inflammatory networks during cellular senescence: causes and consequences. Trends Mol Med 16, 238-246 https://doi.org/10.1016/j.molmed.2010.03.003
  23. Rodier F and Campisi J (2011) Four faces of cellular senescence. J Cell Biol 192, 547-556 https://doi.org/10.1083/jcb.201009094
  24. Campisi J, Andersen JK, Kapahi P and Melov S (2011) Cellular senescence: a link between cancer and age-re-lated degenerative disease? Semin Cancer Biol 21, 354-359
  25. Kim YM, Byun HO, Jee BA et al (2013) Implications of time-series gene expression profiles of replicative senescence. Aging Cell 12, 622-634 https://doi.org/10.1111/acel.12087
  26. Cristofalo VJ, Lorenzini A, Allen RG, Torres C and Tresini M (2004) Replicative senescence: a critical review. Mech Ageing Dev 125, 827-848 https://doi.org/10.1016/j.mad.2004.07.010
  27. Greenberg SB, Grove GL and Cristofalo VJ (1977) Cell size in aging monolayer cultures. In Vitro 13, 297-300 https://doi.org/10.1007/BF02616174
  28. Hwang ES, Yoon G and Kang HT (2009) A comparative analysis of the cell biology of senescence and aging. Cell Mol Life Sci 66, 2503-2524 https://doi.org/10.1007/s00018-009-0034-2
  29. Wang E and Gundersen D (1984) Increased organization of cytoskeleton accompanying the aging of human fibroblasts in vitro. Exp Cell Res 154, 191-202 https://doi.org/10.1016/0014-4827(84)90679-7
  30. Cristofalo VJ and Kritchevsky D (1969) Cell size and nucleic acid content in the diploid human cell line WI-38 during aging. Med Exp Int J Exp Med 19, 313-320
  31. Sherwood SW, Rush D, Ellsworth JL and Schimke RT (1988) Defining cellular senescence in IMR-90 cells: a flow cytometric analysis. Proc Natl Acad Sci U S A 85, 9086-9090 https://doi.org/10.1073/pnas.85.23.9086
  32. Wagner M, Hampel B, Bernhard D, Hala M, Zwerschke W and Jansen-Durr P (2001) Replicative senescence of human endothelial cells in vitro involves G1 arrest, poly-ploidization and senescence-associated apoptosis. Exp Gerontol 36, 1327-1347 https://doi.org/10.1016/S0531-5565(01)00105-X
  33. Takahashi A, Ohtani N and Hara E (2007) Irreversibility of cellular senescence: dual roles of p16INK4a/Rb-pathway in cell cycle control. Cell Div 2, 10 https://doi.org/10.1186/1747-1028-2-10
  34. Serrano M, Lin AW, McCurrach ME, Beach D and Lowe SW (1997) Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell 88, 593-602 https://doi.org/10.1016/S0092-8674(00)81902-9
  35. Kulju KS and Lehman JM (1995) Increased p53 protein associated with aging in human diploid fibroblasts. Exp Cell Res 217, 336-345 https://doi.org/10.1006/excr.1995.1095
  36. Chen X, Zhang W, Gao YF, Su XQ and Zhai ZH (2002) Senescence-like changes induced by expression of p21(waf1/Cip1) in NIH3T3 cell line. Cell Res 12, 229-233 https://doi.org/10.1038/sj.cr.7290129
  37. Malumbres M, Perez De Castro I, Hernandez MI, Jimenez M, Corral T and Pellicer A (2000) Cellular response to on-cogenic ras involves induction of the Cdk4 and Cdk6 inhibitor p15(INK4b). Mol Cell Biol 20, 2915-2925 https://doi.org/10.1128/MCB.20.8.2915-2925.2000
  38. He J, Kallin EM, Tsukada Y and Zhang Y (2008) The H3K36 demethylase Jhdm1b/Kdm2b regulates cell proliferation and senescence through p15(Ink4b). Nat Struct Mol Biol 15, 1169-1175 https://doi.org/10.1038/nsmb.1499
  39. Alcorta DA, Xiong Y, Phelps D, Hannon G, Beach D and Barrett JC (1996) Involvement of the cyclin-dependent kin-ase inhibitor p16 (INK4a) in replicative senescence of normal human fibroblasts. Proc Natl Acad Sci U S A 93, 13742-13747 https://doi.org/10.1073/pnas.93.24.13742
  40. Stein GH, Beeson M and Gordon L (1990) Failure to phos-phorylate the retinoblastoma gene product in senescent human fibroblasts. Science 249, 666-669 https://doi.org/10.1126/science.2166342
  41. Stein GH and Dulic V (1998) Molecular mechanisms for the senescent cell cycle arrest. J Investig Dermatol Symp Proc 3, 14-18
  42. Campisi J and d'Adda di Fagagna F (2007) Cellular senescence: when bad things happen to good cells. Nat Rev Mol Cell Biol 8, 729-740 https://doi.org/10.1038/nrm2233
  43. Fingar DC, Salama S, Tsou C, Harlow E and Blenis J (2002) Mammalian cell size is controlled by mTOR and its downstream targets S6K1 and 4EBP1/eIF4E. Genes Dev 16, 1472-1487 https://doi.org/10.1101/gad.995802
  44. Mamane Y, Petroulakis E, LeBacquer O and Sonenberg N (2006) mTOR, translation initiation and cancer. Oncogene 25, 6416-6422 https://doi.org/10.1038/sj.onc.1209888
  45. Yentrapalli R, Azimzadeh O, Sriharshan A et al (2013) The PI3K/Akt/mTOR pathway is implicated in the premature senescence of primary human endothelial cells ex-posed to chronic radiation. PLoS One 8, e70024 https://doi.org/10.1371/journal.pone.0070024
  46. Kim YM, Shin HT, Seo YH et al (2010) Sterol regulatory element-binding protein (SREBP)-1-mediated lipogenesis is involved in cell senescence. J Biol Chem 285, 29069-29077 https://doi.org/10.1074/jbc.M110.120386
  47. Seo YH, Jung HJ, Shin HT et al (2008) Enhanced glyco-genesis is involved in cellular senescence via GSK3/GS modulation. Aging Cell 7, 894-907 https://doi.org/10.1111/j.1474-9726.2008.00436.x
  48. De Priester W, Van Manen R and Knook DL (1984) Lysosomal activity in the aging rat liver: II. Morphometry of acid phosphatase positive dense bodies. Mech Ageing Dev 26, 205-216 https://doi.org/10.1016/0047-6374(84)90094-0
  49. Yoon YS, Yoon DS, Lim IK et al (2006) Formation of elongated giant mitochondria in DFO-induced cellular senescence: involvement of enhanced fusion process through modulation of Fis1. J Cell Physiol 209, 468-480 https://doi.org/10.1002/jcp.20753
  50. Atadja P, Wong H, Garkavtsev I, Veillette C and Riabowol K (1995) Increased activity of p53 in senescing fibroblasts. Proc Natl Acad Sci U S A 92, 8348-8352 https://doi.org/10.1073/pnas.92.18.8348
  51. Nishio K, Inoue A, Qiao S, Kondo H and Mimura A (2001) Senescence and cytoskeleton: overproduction of vimentin induces senescent-like morphology in human fibroblasts. Histochem Cell Biol 116, 321-327 https://doi.org/10.1007/s004180100325
  52. Kumazaki T, Kobayashi M and Mitsui Y (1993) Enhanced expression of fibronectin during in vivo cellular aging of human vascular endothelial cells and skin fibroblasts. Exp Cell Res 205, 396-402 https://doi.org/10.1006/excr.1993.1103
  53. Eren M, Boe AE, Murphy SB et al (2014) PAI-1-regulated extracellular proteolysis governs senescence and survival in Klotho mice. Proc Natl Acad Sci U S A 111, 7090-7095 https://doi.org/10.1073/pnas.1321942111
  54. Coppe JP, Patil CK, Rodier F et al (2008) Senescence-asso-ciated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol 6, 2853-2868
  55. Vital P, Castro P, Tsang S and Ittmann M (2014) The sen-escence-associated secretory phenotype promotes benign prostatic hyperplasia. Am J Pathol 184, 721-731 https://doi.org/10.1016/j.ajpath.2013.11.015
  56. Brookes S, Rowe J, Gutierrez Del Arroyo A, Bond J and Peters G (2004) Contribution of p16(INK4a) to replicative senescence of human fibroblasts. Exp Cell Res 298, 549-559 https://doi.org/10.1016/j.yexcr.2004.04.035
  57. Kueper T, Grune T, Prahl S et al (2007) Vimentin is the specific target in skin glycation. Structural prerequisites, functional consequences, and role in skin aging. J Biol Chem 282, 23427-23436 https://doi.org/10.1074/jbc.M701586200
  58. Salminen A and Kaarniranta K (2010) Glycolysis links p53 function with NF-kappaB signaling: impact on cancer and aging process. J Cell Physiol 224, 1-6
  59. Childs BG, Durik M, Baker DJ and van Deursen JM (2015) Cellular senescence in aging and age-related disease: from mechanisms to therapy. Nat Med 21, 1424-1435 https://doi.org/10.1038/nm.4000
  60. Bavik C, Coleman I, Dean JP, Knudsen B, Plymate S and Nelson PS (2006) The gene expression program of prostate fibroblast senescence modulates neoplastic epithelial cell proliferation through paracrine mechanisms. Cancer Res 66, 794-802 https://doi.org/10.1158/0008-5472.CAN-05-1716
  61. Wajapeyee N, Serra RW, Zhu X, Mahalingam M and Green MR (2008) Oncogenic BRAF induces senescence and apoptosis through pathways mediated by the secreted protein IGFBP7. Cell 132, 363-374 https://doi.org/10.1016/j.cell.2007.12.032
  62. Parrinello S, Coppe JP, Krtolica A and Campisi J (2005) Stromal-epithelial interactions in aging and cancer: senescent fibroblasts alter epithelial cell differentiation. J Cell Sci 118, 485-496 https://doi.org/10.1242/jcs.01635
  63. Krtolica A, Parrinello S, Lockett S, Desprez PY and Campisi J (2001) Senescent fibroblasts promote epithelial cell growth and tumorigenesis: a link between cancer and aging. Proc Natl Acad Sci U S A 98, 12072-12077 https://doi.org/10.1073/pnas.211053698
  64. Acosta JC, O'Loghlen A, Banito A, Raguz S and Gil J (2008) Control of senescence by CXCR2 and its ligands. Cell Cycle 7, 2956-2959 https://doi.org/10.4161/cc.7.19.6780
  65. Kortlever RM, Higgins PJ and Bernards R (2006) Plasminogen activator inhibitor-1 is a critical downstream target of p53 in the induction of replicative senescence. Nat Cell Biol 8, 877-884 https://doi.org/10.1038/ncb1448
  66. Kuilman T, Michaloglou C, Vredeveld LC et al (2008) Oncogene-induced senescence relayed by an inter-leukin-dependent inflammatory network. Cell 133, 1019-1031 https://doi.org/10.1016/j.cell.2008.03.039
  67. Salminen A, Ojala J, Kaarniranta K, Haapasalo A, Hiltunen M and Soininen H (2011) Astrocytes in the aging brain express characteristics of senescence-associated secretory phenotype. Eur J Neurosci 34, 3-11 https://doi.org/10.1111/j.1460-9568.2011.07738.x
  68. Kumar S, Millis AJ and Baglioni C (1992) Expression of interleukin 1-inducible genes and production of interleukin 1 by aging human fibroblasts. Proc Natl Acad Sci U S A 89, 4683-4687 https://doi.org/10.1073/pnas.89.10.4683
  69. Garfinkel S, Brown S, Wessendorf JH and Maciag T (1994) Post-transcriptional regulation of interleukin 1 alpha in various strains of young and senescent human umbilical vein endothelial cells. Proc Natl Acad Sci U S A 91, 1559-1563 https://doi.org/10.1073/pnas.91.4.1559
  70. Lu SY, Chang KW, Liu CJ et al (2006) Ripe areca nut ex-tract induces G1 phase arrests and senescence-associated phenotypes in normal human oral keratinocyte. Carcinogenesis 27, 1273-1284 https://doi.org/10.1093/carcin/bgi357
  71. Sarkar D, Lebedeva IV, Emdad L, Kang DC, Baldwin AS, Jr. and Fisher PB (2004) Human polynucleotide phosphor-ylase (hPNPaseold-35): a potential link between aging and inflammation. Cancer Res 64, 7473-7478 https://doi.org/10.1158/0008-5472.CAN-04-1772
  72. Orjalo AV, Bhaumik D, Gengler BK, Scott GK and Campisi J (2009) Cell surface-bound IL-1alpha is an upstream regulator of the senescence-associated IL-6/IL-8 cytokine network. Proc Natl Acad Sci U S A 106, 17031-17036 https://doi.org/10.1073/pnas.0905299106
  73. Coppe JP, Patil CK, Rodier F et al (2010) A human-like senescence-associated secretory phenotype is conserved in mouse cells dependent on physiological oxygen. PLoS One 5, e9188 https://doi.org/10.1371/journal.pone.0009188
  74. 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
  75. West MD, Pereira-Smith OM and Smith JR (1989) Replicative senescence of human skin fibroblasts correlates with a loss of regulation and overexpression of colla-genase activity. Exp Cell Res 184, 138-147 https://doi.org/10.1016/0014-4827(89)90372-8
  76. Millis AJ, Hoyle M, McCue HM and Martini H (1992) Differential expression of metalloproteinase and tissue inhibitor of metalloproteinase genes in aged human fibroblasts. Exp Cell Res 201, 373-379 https://doi.org/10.1016/0014-4827(92)90286-H
  77. Zeng G and Millis AJ (1996) Differential regulation of col-lagenase and stromelysin mRNA in late passage cultures of human fibroblasts. Exp Cell Res 222, 150-156 https://doi.org/10.1006/excr.1996.0019
  78. Blasi F and Carmeliet P (2002) uPAR: a versatile signalling orchestrator. Nat Rev Mol Cell Biol 3, 932-943
  79. 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
  80. Brew K, Dinakarpandian D and Nagase H (2000) Tissue inhibitors of metalloproteinases: evolution, structure and function. Biochim Biophys Acta 1477, 267-283 https://doi.org/10.1016/S0167-4838(99)00279-4
  81. Reichenstein M, Reich R, LeHoux JG and Hanukoglu I (2004) ACTH induces TIMP-1 expression and inhibits col-lagenase in adrenal cortex cells. Mol Cell Endocrinol 215, 109-114 https://doi.org/10.1016/j.mce.2003.11.011
  82. Binder BR, Christ G, Gruber F et al (2002) Plasminogen activator inhibitor 1: physiological and pathophysiological roles. News Physiol Sci 17, 56-61
  83. Alessi MC, Poggi M and Juhan-Vague I (2007) Plasminogen activator inhibitor-1, adipose tissue and insulin resistance. Curr Opin Lipidol 18, 240-245 https://doi.org/10.1097/MOL.0b013e32814e6d29
  84. Gils A and Declerck PJ (2004) The structural basis for the pathophysiological relevance of PAI-I in cardiovascular diseases and the development of potential PAI-I inhibitors. Thromb Haemost 91, 425-437
  85. Schroder WA, Major L and Suhrbier A (2011) The role of SerpinB2 in immunity. Crit Rev Immunol 31, 15-30 https://doi.org/10.1615/CritRevImmunol.v31.i1.20
  86. Hwa V, Oh Y and Rosenfeld RG (1999) The insulin-like growth factor-binding protein (IGFBP) superfamily. Endocr Rev 20, 761-787
  87. Stewart CE, Bates PC, Calder TA, Woodall SM and Pell JM (1993) Potentiation of insulin-like growth factor-I (IGF-I) activity by an antibody: supportive evidence for enhancement of IGF-I bioavailability in vivo by IGF binding proteins. Endocrinology 133, 1462-1465 https://doi.org/10.1210/endo.133.3.7689959
  88. Clemmons DR, Busby WH, Arai T et al (1995) Role of in-sulin-like growth factor binding proteins in the control of IGF actions. Prog Growth Factor Res 6, 357-366 https://doi.org/10.1016/0955-2235(95)00013-5
  89. Chow FL and Fernandez-Patron C (2007) Many membrane proteins undergo ectodomain shedding by proteolytic cleavage. Does one sheddase do the job on all of these proteins? IUBMB Life 59, 44-47 https://doi.org/10.1080/15216540600879087
  90. Hayashida K, Bartlett AH, Chen Y and Park PW (2010) Molecular and cellular mechanisms of ectodomain shedding. Anat Rec (Hoboken) 293, 925-937 https://doi.org/10.1002/ar.20757
  91. Athauda G, Giubellino A, Coleman JA et al (2006) c-Met ectodomain shedding rate correlates with malignant potential. Clin Cancer Res 12, 4154-4162 https://doi.org/10.1158/1078-0432.CCR-06-0250
  92. Kenyon C, Chang J, Gensch E, Rudner A and Tabtiang R (1993) A C. elegans mutant that lives twice as long as wild type. Nature 366, 461-464 https://doi.org/10.1038/366461a0
  93. Kenyon C (2005) The plasticity of aging: insights from long-lived mutants. Cell 120, 449-460 https://doi.org/10.1016/j.cell.2005.02.002
  94. Kojima H, Kunimoto H, Inoue T and Nakajima K (2012) The STAT3-IGFBP5 axis is critical for IL-6/gp130-induced premature senescence in human fibroblasts. Cell Cycle 11, 730-739 https://doi.org/10.4161/cc.11.4.19172
  95. Chen D, Yoo BK, Santhekadur PK et al (2011) Insulin-like growth factor-binding protein-7 functions as a potential tumor suppressor in hepatocellular carcinoma. Clin Cancer Res 17, 6693-6701 https://doi.org/10.1158/1078-0432.CCR-10-2774
  96. Micutkova L, Diener T, Li C et al (2011) Insulin-like growth factor binding protein-6 delays replicative senescence of human fibroblasts. Mech Ageing Dev 132, 468-479 https://doi.org/10.1016/j.mad.2011.07.005
  97. Comi P, Chiaramonte R and Maier JA (1995) Senescence-dependent regulation of type 1 plasminogen activator inhibitor in human vascular endothelial cells. Exp Cell Res 219, 304-308 https://doi.org/10.1006/excr.1995.1232
  98. West MD, Shay JW, Wright WE and Linskens MH (1996) Altered expression of plasminogen activator and plasmi-nogen activator inhibitor during cellular senescence. Exp Gerontol 31, 175-193 https://doi.org/10.1016/0531-5565(95)02013-6
  99. Han X and Boisvert WA (2015) Interleukin-10 protects against atherosclerosis by modulating multiple athero-genic macrophage function. Thromb Haemost 113, 505-512 https://doi.org/10.1160/TH14-06-0509