Biomarkers to identify and isolate senescent cells

Ageing Research Reviews

Volumn 29, Issue , 2016, Pages 1-12

  Matjusaitis, Mantas ^a   Chin, Greg ^b   Sarnoski, Ethan Anders ^b   Stolzing, Alexandra ^c,d  

^a UNIVERSITY OF EDINBURGH   (United Kingdom)

^b YALE UNIVERSITY   (United States)

^c UNIVERSITY OF LEIPZIG   (Germany)

^d LOUGHBOROUGH UNIVERSITY   (United Kingdom)

Author keywords

Aging; Biomarkers; Cell biology; Senescence

Indexed keywords

BETA GALACTOSIDASE; BIOLOGICAL MARKER; DNA; MEMBRANE LIPID; PROTEASOME; PROTEIN P16; PROTEIN P21; PROTEIN P53; REACTIVE OXYGEN METABOLITE; RETINOBLASTOMA PROTEIN;

AGING; ATHEROSCLEROSIS; CARCINOGENESIS; CELL AGING; CELL CYCLE ARREST; CELL ISOLATION; CELL PROLIFERATION; CELLS BY DEVELOPMENT; DNA DAMAGE; DNA SYNTHESIS; HUMAN; IMMUNOCYTOCHEMISTRY; IMMUNOSENESCENCE; LIPID COMPOSITION; NERVE DEGENERATION; NONHUMAN; OXIDATIVE STRESS; REPORTER GENE; REVIEW; SENESCENCE; SENESCENT CELL; ANIMAL; BIOLOGICAL THERAPY; CELL SEPARATION; GENETICS; METABOLISM; NEOPLASMS; PHENOTYPE; PHYSIOLOGY; PROCEDURES; TRENDS;

AGING; ANIMALS; ATHEROSCLEROSIS; BIOMARKERS; CELL AGING; CELL SEPARATION; CELL- AND TISSUE-BASED THERAPY; HUMANS; NEOPLASMS; PHENOTYPE;

EID: 84973129659     PISSN: 15681637     EISSN: 18729649     Source Type: Journal    
DOI: 10.1016/j.arr.2016.05.003     Document Type: Review

References (173)

1. Aan G.J., Hairi H.A., Makpol S., Rahman M.A., Karsani S.A. Differences in protein changes between stress-induced premature senescence and replicative senescence states. Electrophoresis 2013, 34:2209-2217. 10.1002/elps.201300086.
2. Aan G.J., H.A.H Differential protein expression in senescent human skin fibroblasts and stress induced premature senescence (SIPS) fibroblasts. Sains Malaysiana 2011, 40:1247-1253.
3. Acosta J.C., O'Loghlen A., Banito A., Guijarro M., Augert V., Raguz A., Fumagalli S., Da Costa M., Brown M., Popov C., Takatsu N., Melamed Y., d'Adda di Fagagna J., Bernard F., Hernando D., Gil E., J Chemokine signaling via the CXCR2 receptor reinforces senescence. Cell 2008, 133:1006-1008. 10.1016/j.cell.2008.03.038.
4. Acosta J.C., Banito A., Wuestefeld T., Georgilis A., Janich P., Morton J.P., Athineos D., Kang T.-W., Lasitschka F., Andrulis M., Pascual G., Morris K.J., Khan S., Jin H., Dharmalingam G., Snijders A.P., Carroll T., Capper D., Pritchard C., Inman G.J., Longerich T., Sansom O.J., Benitah S.A., Zender L., Gil J. A complex secretory program orchestrated by the inflammasome controls paracrine senescence. Nat. Cell Biol. 2013, 15:978-990. 10.1038/ncb2784.
5. Aird K.M., Zhang R. Detection of senescence-associated heterochromatin foci (SAHF). Methods Mol. Biol. 2013, 965:185-196. 10.1007/978-1-62703-239-1_12.
6. Althubiti M., Lezina L., Carrera S., Jukes-Jones R., Giblett S.M., Antonov A., Barlev N., Saldanha G.S., Pritchard C.A., Cain K., Macip S. Characterization of novel markers of senescence and their prognostic potential in cancer. Cell Death Dis. 2014, 5:e1528. 10.1038/cddis.2014.489.
7. Amaral J.D., Xavier J.M., Steer C.J., Rodrigues C.M. The role of p53 in apoptosis. Discov. Med. 2010, 9:145-152.
8. Awasthi P., Foiani M., Kumar A. ATM and ATR signaling at a glance. J. Cell Sci. 2015, 128:4255-4262. 10.1242/jcs.169730.
9. Badie S., Escandell J.M., Bouwman P., Carlos A.R., Thanasoula M., Gallardo M.M., Suram A., Jaco I., Benitez J., Herbig U., Blasco M.A., Jonkers J., Tarsounas M. BRCA2 acts as a RAD51 loader to facilitate telomere replication and capping. Nat. Struct. Mol. Biol. 2010, 17:1461-1469. 10.1038/nsmb.1943.
10. Baerlocher G.M., Vulto I., de Jong G., Lansdorp P.M. Flow cytometry and FISH to measure the average length of telomeres (flow FISH). Nat. Protoc. 2006, 1:2365-2376. 10.1038/nprot.2006.263.
11. Baker D.J., Wijshake T., Tchkonia T., LeBrasseur N.K., Childs B.G., van de Sluis B., Kirkland J.L., van Deursen J.M. Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature 2011, 479:232-236. 10.1038/nature10600.
12. Baker D.J., Childs B.G., Durik M., Wijers M.E., Sieben C.J., Zhong J., Saltness R.A., Jeganathan K.B., Casaclang Verzosa G., Pezeshki A., Khazaie K., Miller J.D., Van Deursen J.M. Naturally occurring p16 Ink4a-positive cells shorten healthy lifespan. Nature 2016, 530:184-189. 10.1038/nature16932.
13. Barker S.D., Dmitriev I.P., Nettelbeck D.M., Liu B., Rivera A.A., Alvarez R.D., Curiel D.T., Hemminki A. Combined transcriptional and transductional targeting improves the specificity and efficacy of adenoviral gene delivery to ovarian carcinoma. Gene Ther. 2003, 10:1198-1204. 10.1038/sj.gt.3301974.
14. Bartkova J., Rezaei N., Liontos M., Karakaidos P., Kletsas D., Issaeva N., Vassiliou L.-V.F., Kolettas E., Niforou K., Zoumpourlis V.C., Takaoka M., Nakagawa H., Tort F., Fugger K., Johansson F., Sehested M., Andersen C.L., Dyrskjot L., Ørntoft T., Lukas J., Kittas C., Helleday T., Halazonetis T.D., Bartek J., Gorgoulis V.G. Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints. Nature 2006, 444:633-637. 10.1038/nature05268.
15. Bassaneze V., Miyakawa A.A., Krieger J.E. A quantitative chemiluminescent method for studying replicative and stress-induced premature senescence in cell cultures. Anal. Biochem. 2008, 372:198-203. 10.1016/j.ab.2007.08.016.
16. Beauséjour C.M., Krtolica A., Galimi F., Narita M., Lowe S.W., Yaswen P., Campisi J. Reversal of human cellular senescence: roles of the p53 and p16 pathways. EMBO J. 2003, 22:4212-4222. 10.1093/emboj/cdg417.
17. Beech J.P., Holm S.H., Adolfsson K., Tegenfeldt J.O. Sorting cells by size, shape and deformability. Lab Chip 2012, 12:1048-1051. 10.1039/c2lc21083e.
18. Bekaert S., De Meyer T., Van Oostveldt P. Telomere attrition as ageing biomarker. Anticancer Res. 2005, 25:3011-3021.
19. Biran A., Krizhanovsky V. Senescent cells talk frankly with their neighbors. Cell Cycle 2015, 14:2181-2182. 10.1080/15384101.2015.1056608.
20. Blondal J.A., Dick J.E., Wright J.A. Membrane glycoprotein changes during the senescence of normal human diploid fibroblasts in culture. Mech. Ageing Dev. 1985, 30:273-283.
21. Braig M., Pällmann N., Preukschas M., Steinemann D., Hofmann W., Gompf A., Streichert T., Braunschweig T., Copland M., Rudolph K.L., Bokemeyer C., Koschmieder S., Schuppert A., Balabanov S., Brümmendorf T.H. A telomere-associated secretory phenotype cooperates with BCR-ABL to drive malignant proliferation of leukemic cells. Leukemia 2014, 10.1038/leu.2014.95.
22. Brown D.A. Lipid rafts, detergent-resistant membranes, and raft targeting signals. Physiology (Bethesda) 2006, 21:430-439. 10.1152/physiol.00032.2006.
23. Brugat T., Nguyen-Khac F., Grelier A., Merle-Béral H., Delic J. Telomere dysfunction-induced foci arise with the onset of telomeric deletions and complex chromosomal aberrations in resistant chronic lymphocytic leukemia cells. Blood 2010, 116:239-249. 10.1182/blood-2009-12-257618.
24. Burton D.G.A., Faragher R.G.A. Cellular senescence: from growth arrest to immunogenic conversion. Age (Omaha) 2015, 37:1-19. 10.1007/s11357-015-9764-2.
25. Cai L., Yang Y., Jiao N., Zhang R. Evaluation of tangential flow filtration for the concentration and separation of bacteria and viruses in contrasting marine environments. PLoS One 2015, 10:e0136741. 10.1371/journal.pone.0136741.
26. Campisi J., d' F., Adda di Fagagna Cellular senescence: when bad things happen to good cells. Nat. Rev. Mol. Cell Biol. 2007, 8:729-740. 10.1038/nrm2233.
27. Campisi J., Nelson P., Patil C., Coppé J.-P., Rodier F., Sun Y., Goldstein J., Munoz D., Desprez P.-Y. Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. Public Libr. Sci. 2008.
28. Campisi J., Andersen J.K., Kapahi P., Melov S. Cellular senescence: a link between cancer and age-related degenerative disease?. Semin. Cancer Biol. 2011, 21:354-359. 10.1016/j.semcancer.2011.09.001.
29. Campisi J. The biology of replicative senescence. Eur. J. Cancer 1997, 33:703-709. 10.1016/S0959-8049(96)00058-5.
30. Campisi J. Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors. Cell 2005, 120:513-522. 10.1016/j.cell.2005.02.003.
31. Cawthon R.M. Telomere measurement by quantitative PCR. Nucleic Acids Res. 2002, 30:e47.
32. Chang J., Wang Y., Shao L., Laberge R.-M., Demaria M., Campisi J., Janakiraman K., Sharpless N.E., Ding S., Feng W., Luo Y., Wang X., Aykin-Burns N., Krager K., Ponnappan U., Hauer-Jensen M., Meng A., Zhou D. Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice. Nat. Med. 2016, 22:78-83. 10.1038/nm.4010.
33. Chapman J.R., Taylor M.R.G., Boulton S.J. Playing the end game: DNA double-strand break repair pathway choice. Mol. Cell 2012, 47:497-510. 10.1016/j.molcel.2012.07.029.
34. Chen J.-H., Hales C.N., Ozanne S.E. DNA damage, cellular senescence and organismal ageing: causal or correlative?. Nucleic Acids Res. 2007, 35:7417-7428. 10.1093/nar/gkm681.
35. Chondrogianni N., Gonos E.S. Proteasome inhibition induces a senescence-like phenotype in primary human fibroblasts cultures. Biogerontology 2004, 5:55-61.
36. Chondrogianni N., Stratford F.L.L., Trougakos I.P., Friguet B., Rivett A.J., Gonos E.S. Central role of the proteasome in senescence and survival of human fibroblasts: induction of a senescence-like phenotype upon its inhibition and resistance to stress upon its activation. J. Biol. Chem. 2003, 278:28026-28037. 10.1074/jbc.M301048200.
37. Christensen K., Doblhammer G., Rau R., Vaupel J.W. Ageing populations: the challenges ahead. Lancet 2009, 374:1196-1208. 10.1016/S0140-6736(09)61460-4.
38. Coppé J.-P., Patil C.K., Rodier F., Sun Y., Muñoz D.P., Goldstein J., Nelson P.S., Desprez P.-Y., Campisi J. Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol. 2008, 6:2853-2868. 10.1371/journal.pbio.0060301.
39. Coppé J.-P., Desprez P.-Y., Krtolica A., Campisi J. The senescence-associated secretory phenotype: the dark side of tumor suppression. Annu. Rev. Pathol. 2010, 5:99-118. 10.1146/annurev-pathol-121808-102144.
40. Cosgrove B.D., Gilbert P.M., Porpiglia E., Mourkioti F., Lee S.P., Corbel S.Y., Llewellyn M.E., Delp S.L., Blau H.M. Rejuvenation of the muscle stem cell population restores strength to injured aged muscles. Nat. Med. 2014, 20:255-264. 10.1038/nm.3464.
41. Darling E.M., Topel M., Zauscher S., Vail T.P., Guilak F. Viscoelastic properties of human mesenchymally-derived stem cells and primary osteoblasts, chondrocytes, and adipocytes. J. Biomech. 2008, 41:454-464. 10.1016/j.jbiomech.2007.06.019.
42. De Cecco M., Jeyapalan J., Zhao X., Tamamori-Adachi M., Sedivy J.M. Nuclear protein accumulation in cellular senescence and organismal aging revealed with a novel single-cell resolution fluorescence microscopy assay. Aging (Albany. NY) 2011, 3:955-967.
43. Debacq-Chainiaux F., Erusalimsky J.D., 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, 4:1798-1806. 10.1038/nprot.2009.191.
44. Demaria M., Ohtani N., Youssef S.A., Rodier F., Toussaint W., Mitchell J.R., Laberge R.-M., Vijg J., Van Steeg H., Dollé M.E.T., Hoeijmakers J.H.J., 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, 31:722-733. 10.1016/j.devcel.2014.11.012.
45. Dierick J.-F., Eliaers F., Remacle J., Raes M., Fey S.J., Larsen P.M., Toussaint O. Stress-induced premature senescence and replicative senescence are different phenotypes proteomic evidence. Biochem. Pharmacol. 2002, 64:1011-1017.
46. Dimri G.P., Lee X., Basile G., Acosta M., Scott G., Roskelley C., Medrano E.E., 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. U. S. A. 1995, 92:9363-9367.
47. Dumitrescu R.G. Epigenetic markers of early tumor development. Methods Mol. Biol. 2012, 863:3-14. 10.1007/978-1-61779-612-8_1.
48. Elsedawy N.B., Russell S.J. Oncolytic vaccines. Expert Rev. Vaccines 2013, 12:1155-1172. 10.1586/14760584.2013.836912.
49. Erusalimsky J.D., Kurz D.J. Cellular senescence in vivo: its relevance in ageing and cardiovascular disease. Exp. Gerontol. 2005, 40:634-642. 10.1016/j.exger.2005.04.010.
50. Espinoza S.E., Guo H., Fedarko N., DeZern A., Fried L.P., Xue Q.-L., Leng S., Beamer B., Walston J.D. Glutathione peroxidase enzyme activity in aging. J. Gerontol. A Biol. Sci. Med. Sci. 2008, 63:505-509.
51. Everts M., Curiel D.T. Transductional targeting of adenoviral cancer gene therapy. Curr. Gene Ther. 2004, 4:337-346.
52. Falandry C., Gilson E., Rudolph K.L. Are aging biomarkers clinically relevant in oncogeriatrics?. Crit. Rev. Oncol. Hematol. 2013, 85:257-265. 10.1016/j.critrevonc.2012.08.004.
53. Fan L.M., Li J.-M. Evaluation of methods of detecting cell reactive oxygen species production for drug screening and cell cycle studies. J. Pharmacol. Toxicol. Methods 2014, 70:40-47. 10.1016/j.vascn.2014.03.173.
54. Fan L.M., Li J.-M. Evaluation of methods of detecting cell reactive oxygen species production for drug screening and cell cycle studies. J. Pharmacol. Toxicol. Methods 2016, 70:40-47. 10.1016/j.vascn.2014.03.173.
55. Ferbeyre G., de Stanchina E., Querido E., Baptiste N., Prives C., Lowe S.W. PML is induced by oncogenic ras and promotes premature senescence. Genes Dev. 2000, 14:2015-2027.
56. Fischer B.M., Wong J.K., Degan S., Kummarapurugu A.B., Zheng S., Haridass P., Voynow J.A. Increased expression of senescence markers in cystic fibrosis airways. Am. J. Physiol. Lung Cell. Mol. Physiol. 2013, 304:L394-400. 10.1152/ajplung.00091.2012.
57. Fulop T., Le Page A., Garneau H., Azimi N., Baehl S., Dupuis G., Pawelec G., Larbi A. Aging, immunosenescence and membrane rafts: the lipid connection. Longev. Health 2012, 1:6. 10.1186/2046-2395-1-6.
58. Fumagalli M., Rossiello F., Clerici M., Barozzi S., Cittaro D., Kaplunov J.M., Bucci G., Dobreva M., Matti V., Beausejour C.M., Herbig U., Longhese M.P., d' F., Adda di Fagagna Telomeric DNA damage is irreparable and causes persistent DNA-damage-response activation. Nat. Cell Biol. 2012, 14:355-365. 10.1038/ncb2466.
59. Garber K. China approves world's first oncolytic virus therapy for cancer treatment. J. Natl. Cancer Inst. 2006, 98:298-300. 10.1093/jnci/djj111.
60. García-Prat L., Martínez-Vicente M., Perdiguero E., Ortet L., Rodríguez-Ubreva J., Rebollo E., Ruiz-Bonilla V., Gutarra S., Ballestar E., Serrano A.L., Sandri M., Muñoz-Cánoves P. Autophagy maintains stemness by preventing senescence. Nature 2016, 529:37-42. 10.1038/nature16187.
61. Georgila K., Voutetakis K., Delitsikou V., Chondrogianni N., Gonos E.S. Optimization of in vitro measurement of proteasome activity in mammalian cells using fluorogenic substrates. Free Radic. Biol. Med. 2014, 75(Suppl 1):S31. 10.1016/j.freeradbiomed.2014.10.762.
62. Ghosh A.K., Kanda T., Steele R., Ray R.B. Knockdown of MBP-1 in human foreskin fibroblasts induces p53-p21 dependent senescence. PLoS One 2008, 3:e3384. 10.1371/journal.pone.0003384.
63. Golde T.E., Miller V.M. Proteinopathy-induced neuronal senescence: a hypothesis for brain failure in Alzheimer's and other neurodegenerative diseases. Alzheimers Res. Ther. 2009, 1:5. 10.1186/alzrt5.
64. Gratzner H.G. Monoclonal antibody to 5-bromo- and 5-iododeoxyuridine: a new reagent for detection of DNA replication. Science 1982, 218:474-475.
65. Gu L., Kitamura M. Sensitive detection and monitoring of senescence-associated secretory phenotype by SASP-RAP assay. PLoS One 2012, 7:e52305. 10.1371/journal.pone.0052305.
66. Guo X., Keyes W.M., Papazoglu C., Zuber J., Li W., Lowe S.W., Vogel H., Mills A.A. TAp63 induces senescence and suppresses tumorigenesis in vivo. Nat. Cell Biol. 2009, 11:1451-1457. 10.1038/ncb1988.
67. Harman D. Aging: a theory based on free radical and radiation chemistry. J. Gerontol. 1956, 11:298-300.
68. Harper S. Economic and social implications of aging societies. Science 2014, 346:587-591. 10.1126/science.1254405.
69. Hayflick L. The limited in vitro lifetime of human diploid cell strains. Exp. Cell Res. 1965, 37:614-636.
70. Henry N.L., Hayes D.F. Cancer biomarkers. Mol. Oncol. 2012, 6:140-146. 10.1016/j.molonc.2012.01.010.
71. Herbig U., Ferreira M., Condel L., Carey D., Sedivy J.M. Cellular senescence in aging primates. Science 2006, 311:1257. 10.1126/science.1122446.
72. Hildebrand D.G., Lehle S., Borst A., Haferkamp S., Essmann F., Schulze-Osthoff K. α-Fucosidase as a novel convenient biomarker for cellular senescence. Cell Cycle 2013, 12:1922-1927. 10.4161/cc.24944.
73. Hipkiss A.R. Accumulation of altered proteins and ageing: causes and effects. Exp. Gerontol. 2006, 41:464-473. 10.1016/j.exger.2006.03.004.
74. Holleran B.J. Differential recruitment of alpha2beta1 and alpha4beta1 integrins to lipid rafts in jurkat T lymphocytes exposed to collagen type IV and fibronectin. J. Leukoc. Biol. 2003, 73:243-252. 10.1189/jlb.0902439.
75. Horvath S. DNA methylation age of human tissues and cell types. Genome Biol. 2013, 14:R115. 10.1186/gb-2013-14-10-r115.
76. Huang Y., Corbley M.J., Tang Z., Yang L., Peng Y., Zhang Z.Y., Tong T.J. Down-regulation of p21WAF1 promotes apoptosis in senescent human fibroblasts: involvement of retinoblastoma protein phosphorylation and delay of cellular aging. J. Cell. Physiol. 2004, 201:483-491. 10.1002/jcp.20125.
77. Hultdin M., Gronlund E., Norrback K.-F., Eriksson-Lindstrom E., Roos G., Just T. Telomere analysis by fluorescence in situ hybridization and flow cytometry. Nucleic Acids Res. 1998, 26:3651-3656. 10.1093/nar/26.16.3651.
78. Ide T., Tsuji Y., Ishibashi S., Mitsui Y. Reinitiation of host DNA synthesis in senescent human diploid cells by infection with simian virus 40. Exp. Cell Res. 1983, 143:343-349.
79. Irvine K.M., Skoien R., Bokil N.J., Melino M., Thomas G.P., Loo D., Gabrielli B., Hill M.M., Sweet M.J., Clouston A.D., Powell E.E. Senescent human hepatocytes express a unique secretory phenotype and promote macrophage migration. World J. Gastroenterol. 2014, 20:17851-17862. 10.3748/wjg.v20.i47.17851.
80. Jeyapalan J.C., Ferreira M., Sedivy J.M., Herbig U. Accumulation of senescent cells in mitotic tissue of aging primates. Mech. Ageing Dev. 2007, 128:36-44. 10.1016/j.mad.2006.11.008.
81. Jiang H., Schiffer E., Song Z., Wang J., Zürbig P., Thedieck K., Moes S., Bantel H., Saal N., Jantos J., Brecht M., Jenö P., Hall M.N., Hager K., Manns M.P., Hecker H., Ganser A., Döhner K., Bartke A., Meissner C., Mischak H., Ju Z., Rudolph K.L. Proteins induced by telomere dysfunction and DNA damage represent biomarkers of human aging and disease. Proc. Natl. Acad. Sci. U. S. A. 2008, 105:11299-11304. 10.1073/pnas.0801457105.
82. Jones B. Epigenetics: detecting the dynamics and memory of heterochromatin. Nat. Rev. Genet. 2012, 13:517. 10.1038/nrg3283.
83. Kabouridis P.S. Lipid rafts in T cell receptor signalling. Mol. Membr. Biol. 2006, 23:49-57. 10.1080/09687860500453673.
84. Kankeu H.T., Saksena P., Xu K., Evans D.B. The financial burden from non-communicable diseases in low- and middle-income countries: a literature review. Health Res. Policy Syst. 2013, 11:31. 10.1186/1478-4505-11-31.
85. Kennedy S.R., Loeb L.A., Herr A.J. Somatic mutations in aging, cancer and neurodegeneration. Mech. Ageing Dev. 2012, 133:118-126. 10.1016/j.mad.2011.10.009.
86. Kim M.S., Jo S., Park J.T., Shin H.Y., Kim S.S., Gurel O., Park S.C. Method to purify and analyze heterogeneous senescent cell populations using a microfluidic filter with uniform fluidic profile. Anal. Chem. 2015, 87:9584-9588. 10.1021/acs.analchem.5b00445.
87. Kosar M., Bartkova J., Hubackova S., Hodny Z., Lukas J., Bartek J. Senescence-associated heterochromatin foci are dispensable for cellular senescence, occur in a cell type- and insult-dependent manner and follow expression of p16(ink4a). Cell Cycle 2011, 10:457-468.
88. Krishnamurthy J., Torrice C., Ramsey M.R., Kovalev G.I., Al-Regaiey K., Su L., Sharpless N.E. Ink4a/Arf expression is a biomarker of aging. J. Clin. Invest. 2004, 114:1299-1307. 10.1172/JCI22475.
89. Kuilman T., Michaloglou C., Vredeveld L.C.W., Douma S., van Doorn R., Desmet C.J., Aarden L.A., Mooi W.J., Peeper D.S. Oncogene-induced senescence relayed by an interleukin-dependent inflammatory network. Cell 2008, 133:1019-1031. 10.1016/j.cell.2008.03.039.
90. Kurz D.J., Decary S., Hong Y., Erusalimsky J.D. Senescence-associated (beta)-galactosidase reflects an increase in lysosomal mass during replicative ageing of human endothelial cells. J. Cell Sci. 2000, 113:3613-3622. (Pt 2).
91. Lagerholm B.C., Weinreb G.E., Jacobson K., Thompson N.L. Detecting microdomains in intact cell membranes. Annu. Rev. Phys. Chem. 2005, 56:309-336. 10.1146/annurev.physchem.56.092503.141211.
92. Larbi A., Douziech N., Dupuis G., Khalil A., Pelletier H. Age-associated alterations in the recruitment of signal- transduction proteins to lipid rafts in human T lymphocytes abstract: aging is associated with a decline in T cell activation and proliferation, but the underlying ings suggest that lipid rafts ac. J. Leukoc. Biol. 2004, 75:373-381. 10.1189/jlb.0703319.1.
93. Larbi A., Dupuis G., Khalil A., Douziech N., Fortin C., Fülöp T. Differential role of lipid rafts in the functions of CD4+ and CD8+ human T lymphocytes with aging. Cell Signal. 2006, 18:1017-1030. 10.1016/j.cellsig.2005.08.016.
94. Larson C., Oronsky B., Scicinski J., Fanger G.R., Stirn M., Oronsky A., Reid T.R. Going viral: a review of replication-selective oncolytic adenoviruses. Oncotarget 2015, 6:19976-19989.
95. Lawless C., Wang C., Jurk D., Merz A., Zglinicki T., von Passos J.F. Quantitative assessment of markers for cell senescence. Exp. Gerontol. 2010, 45:772-778. 10.1016/j.exger.2010.01.018.
96. Lee C.Y.F., Bu L.X.X., DeBenedetti A., Williams B.J., Rennie P.S., Jia W.W.G. Transcriptional and translational dual-regulated oncolytic herpes simplex virus type 1 for targeting prostate tumors. Mol. Ther. 2010, 18:929-935. 10.1038/mt.2010.26.
97. Leikam C., Hufnagel A.L., Otto C., Murphy D.J., Mühling B., Kneitz S., Nanda I., Schmid M., Wagner T.U., Haferkamp S., Bröcker E.-B., Schartl M., Meierjohann S. In vitro evidence for senescent multinucleated melanocytes as a source for tumor-initiating cells. Cell Death Dis. 2015, 6:e1711. 10.1038/cddis.2015.71.
98. Li L., Bhatia R. Stem cell quiescence. Clin. Cancer Res. 2011, 17:4936-4941. 10.1158/1078-0432.CCR-10-1499.
99. Li Y., Yuan H., Yang K., Xu W., Tang W., Li X. The structure and functions of P-glycoprotein. Curr. Med. Chem. 2010, 17:786-800.
100. Liochev S.I. Reactive oxygen species and the free radical theory of aging. Free Radic. Biol. Med. 2013, 60:1-4. 10.1016/j.freeradbiomed.2013.02.011.
101. Liu H., Ding Y., Voskuhl R.R. Method to detect functional estrogen receptor expression using estrogen receptor probing compound. J. Immunoassay Immunochem. 2005, 26:295-301. 10.1080/15321810500220894.
102. Lu Y.-Y., Yang X., Chen W.-Q., Ju Z.-Y., Shou Z.-F., Jin J., Zhang X.-H., Chen J.-H., Jiang H. Proteins induced by telomere dysfunction are associated with human IgA nephropathy. J. Zhejiang Univ. Sci. B 2014, 15:566-574. 10.1631/jzus.B1300115.
103. Lynch M.D. The role of cellular senescence may be to prevent proliferation of neighboring cells within stem cell niches. Ann. N. Y. Acad. Sci. 2004, 1019:191-194. 10.1196/annals.1297.030.
104. Mäbert K., Cojoc M., Peitzsch C., Kurth I., Souchelnytskyi S., Dubrovska A. Cancer biomarker discovery: current status and future perspectives. Int. J. Radiat. Biol. 2014, 90:659-677. 10.3109/09553002.2014.892229.
105. Maciel-Barón L.A., Morales-Rosales S.L., Aquino-Cruz A.A., Triana-Martínez F., Galván-Arzate S., Luna-López A., González-Puertos V.Y., López-Díazguerrero N.E., Torres C., Königsberg M. Senescence associated secretory phenotype profile from primary lung mice fibroblasts depends on the senescence induction stimuli. Age (Dordr) 2016, 38:26. 10.1007/s11357-016-9886-1.
106. Mather K.A., Jorm A.F., Parslow R.A., Christensen H. Is telomere length a biomarker of aging? A review. J. Gerontol. A Biol. Sci. Med. Sci. 2011, 66:202-213. 10.1093/gerona/glq180.
107. Melk A., Schmidt B.M.W., Braun H., Vongwiwatana A., Urmson J., Zhu L.-F., Rayner D., Halloran P.F. Effects of donor age and cell senescence on kidney allograft survival. Am. J. Transplant. 2009, 9:114-123. 10.1111/j.1600-6143.2008.02500.x.
108. Mikhalyov I., Samsonov A. Lipid raft detecting in membranes of live erythrocytes. Biochim. Biophys. Acta 2011, 1808:1930-1939. 10.1016/j.bbamem.2011.04.002.
109. Momchilova A., Petkova D., Staneva G., Markovska T., Pankov R., Skrobanska R., Nikolova-Karakashian M., Koumanov K. Resveratrol alters the lipid composition, metabolism and peroxide level in senescent rat hepatocytes. Chem. Biol. Interact. 2014, 207:74-80. 10.1016/j.cbi.2013.10.016.
110. Muñoz-Espín D., Cañamero M., Maraver A., Gómez-López G., Contreras J., Murillo-Cuesta S., Rodríguez-Baeza A., Varela-Nieto I., Ruberte J., Collado M., Serrano M. Programmed cell senescence during mammalian embryonic development. Cell 2013, 155:1104-1118. 10.1016/j.cell.2013.10.019.
111. Muller P.A.J., Vousden K.H. p53 mutations in cancer. Nat. Cell Biol. 2013, 15:2-8. 10.1038/ncb2641.
112. Narita M., Nũnez S., Heard E., Narita M., Lin A.W., Hearn S.A., Spector D.L., Hannon G.J., Lowe S.W. Rb-mediated heterochromatin formation and silencing of E2 F target genes during cellular senescence. Cell 2003, 113:703-716.
113. Narita M. Cellular senescence and chromatin organisation. Br. J. Cancer 2007, 96:686-691. 10.1038/sj.bjc.6603636.
114. Nishimatsu H., Suzuki E., Saito Y., Niimi A., Nomiya A., Fukuhara H., Kume H., Homma Y. Senescent cells impair erectile function through induction of endothelial dysfunction and nerve injury in mice. PLoS One 2015, 10:e0124129. 10.1371/journal.pone.0124129.
115. O' N.J., Callaghan, Fenech M. A quantitative PCR method for measuring absolute telomere length. Biol. Proced. 2011, 13:3. (Online). 10.1186/1480-9222-13-3.
116. O'sullivan J.N., Finley J.C., Risques R.-A., Shen W.-T., Gollahon K.A., Rabinovitch P.S. Quantitative fluorescence in situ hybridization (QFISH) of telomere lengths in tissue and cells. Curr. Protoc. Cytom. 2005, (Chapter 12, Unit 12.6). 10.1002/0471142956.cy1206s33.
117. Obradovic J., Jurisic V. Evaluation of current methods to detect the mutations of epidermal growth factor receptor in non-small cell lung cancer patients. Multidiscip. Respir. Med. 2012, 7:52. 10.1186/2049-6958-7-52.
118. Oishi T., Imai H., Go Y., Imamura M., Hirai H., Takada M. Sporadic premature aging in a Japanese monkey: a primate model for progeria. PLoS One 2014, 9:e111867. 10.1371/journal.pone.0111867.
119. Ourliac-Garnier I., Londoño-Vallejo A. Telomere length analysis by quantitative fluorescent in situ hybridization (Q-FISH). Methods Mol. Biol. 2011, 735:21-31. 10.1007/978-1-61779-092-8_3.
120. Pallis A.G., Hatse S., Brouwers B., Pawelec G., Falandry C., Wedding U., Lago L.D., Repetto L., Ring A., Wildiers H. Evaluating the physiological reserves of older patients with cancer: the value of potential biomarkers of aging?. J. Geriatr. Oncol. 2014, 5:204-218. 10.1016/j.jgo.2013.09.001.
121. Paradis V., Youssef N., Dargère D., Bâ N., Bonvoust F., Deschatrette J., Bedossa P. Replicative senescence in normal liver, chronic hepatitis C, and hepatocellular carcinomas. Hum. Pathol. 2001, 32:327-332. 10.1053/hupa.2001.22747.
122. Park D.C., Yeo S.G. Aging. Korean J. Audiol. 2013, 17:39-44. 10.7874/kja.2013.17.2.39.
123. Parrinello S., Coppe J.-P., Krtolica A., Campisi J. Stromal-epithelial interactions in aging and cancer: senescent fibroblasts alter epithelial cell differentiation. J. Cell Sci. 2005, 118:485-496. 10.1242/jcs.01635.
124. Paul A., Belton A., Nag S., Martin I., Grotewiel M.S., Duttaroy A. Reduced mitochondrial SOD displays mortality characteristics reminiscent of natural aging. Mech. Ageing Dev. 2007, 128:706-716. 10.1016/j.mad.2007.10.013.
125. Paul M.K., Bisht B., Darmawan D.O., Chiou R., Ha V.L., Wallace W.D., Chon A.T., Hegab A.E., Grogan T., Elashoff D.A., Alva-Ornelas J.A., Gomperts B.N. Dynamic changes in intracellular ROS levels regulate airway basal stem cell homeostasis through Nrf2-dependent notch signaling. Cell Stem Cell 2014, 15:199-214. 10.1016/j.stem.2014.05.009.
126. Perez J.T., García-Sastre A., Manicassamy B. Insertion of a GFP reporter gene in influenza virus. Curr. Protoc. Microbiol. 2013, (Chapter 15, Unit 15G.4). 10.1002/9780471729259.mc15g04s29.
127. Pol J., Kroemer G., Galluzzi L. First oncolytic virus approved for melanoma immunotherapy. Oncoimmunology 2015, 5:e1115641. 10.1080/2162402X.2015.1115641.
128. Pontes B., Ayala Y., Fonseca A.C.C., Romão L.F., Amaral R.F., Salgado L.T., Lima F.R., Farina M., Viana N.B., Moura-Neto V., Nussenzveig H.M. Membrane elastic properties and cell function. PLoS One 2013, 8:e67708. 10.1371/journal.pone.0067708.
129. Poot M., Verkerk A., Jongkind J.F. Accumulation of a high molecular weight glycoprotein during in vitro ageing and contact inhibition of growth. Mech. Ageing Dev. 1986, 34:219-232.
130. Reinheckel T., Sitte N., Ullrich O., Kuckelkorn U., Davies K.J., Grune T. Comparative resistance of the 20 S and 26 S proteasome to oxidative stress. Biochem. J. 1998, 335:637-642. (Pt 3).
131. Riess O., Krüger R. Parkinson's disease-a multifactorial neurodegenerative disorder. J. Neural. Transm. 1999, (Suppl. 56):113-125.
132. Rodier F., Campisi J. Four faces of cellular senescence. J. Cell Biol. 2011, 192:547-556. 10.1083/jcb.201009094.
133. Rodier F., Coppé J.-P., Patil C.K., Hoeijmakers W.A.M., Muñoz D.P., Raza S.R., Freund A., Campeau E., Davalos A.R., Campisi J. Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion. Nat. Cell Biol. 2009, 11:973-979. 10.1038/ncb1909.
134. Rodier F. Detection of the senescence-associated secretory phenotype (SASP). Methods Mol. Biol. 2013, 965:165-173. 10.1007/978-1-62703-239-1_10.
135. Rossi M.L., Ghosh A.K., Bohr V.A. Roles of Werner syndrome protein in protection of genome integrity. DNA Repair (Amst) 2010, 9:331-344. 10.1016/j.dnarep.2009.12.011.
136. Sahin E., Colla S., Liesa M., Moslehi J., Müller F.L., Guo M., Cooper M., Kotton D., Fabian A.J., Walkey C., Maser R.S., Tonon G., Foerster F., Xiong R., Wang Y.A., Shukla S.A., Jaskelioff M., Martin E.S., Heffernan T.P., Protopopov A., Ivanova E., Mahoney J.E., Kost-Alimova M., Perry S.R., Bronson R., Liao R., Mulligan R., Shirihai O.S., Chin L., DePinho R.A. Telomere dysfunction induces metabolic and mitochondrial compromise. Nature 2011, 470:359-365. 10.1038/nature09787.
137. Salama R., Sadaie M., Hoare M., Narita M. Cellular senescence and its effector programs. Genes Dev. 2014, 28:99-114. 10.1101/gad.235184.113.
138. Salic A., Mitchison T.J. A chemical method for fast and sensitive detection of DNA synthesis in vivo. Proc. Natl. Acad. Sci. U. S. A. 2008, 105:2415-2420. 10.1073/pnas.0712168105.
139. Sandeman S.R., Faragher R.G., Allen M.C., Liu C., Lloyd A.W. Does MMP-2 expression and secretion change with increasing serial passage of keratocytes in culture?. Mech. Ageing Dev. 2001, 122:157-167.
140. Schnabl B., Purbeck C.A., Choi Y.H., Hagedorn C.H., Brenner D. Replicative senescence of activated human hepatic stellate cells is accompanied by a pronounced inflammatory but less fibrogenic phenotype. Hepatology 2003, 37:653-664. 10.1053/jhep.2003.50097.
141. Sedelnikova O.A., Horikawa I., Zimonjic D.B., Popescu N.C., Bonner W.M., Barrett J.C. Senescing human cells and ageing mice accumulate DNA lesions with unrepairable double-strand breaks. Nat. Cell Biol. 2004, 6:168-170. 10.1038/ncb1095.
142. Sharma A., Singh K., Almasan A. Histone H2AX phosphorylation: a marker for DNA damage. Methods Mol. Biol. 2012, 920:613-626. 10.1007/978-1-61779-998-3_40.
143. Shay J.W., Pereira-Smith O.M., Wright W.E. A role for both RB and p53 in the regulation of human cellular senescence. Exp. Cell Res. 1991, 196:33-39.
144. Sheikh S., Haque E., Mir S.S. Neurodegenerative diseases: multifactorial conformational diseases and their therapeutic interventions. J. Neurodegener. Dis. 2013, 2013:1-8. 10.1155/2013/563481.
145. Sinclair D.A., Oberdoerffer P. The ageing epigenome: damaged beyond repair?. Ageing Res. Rev. 2009, 8:189-198. 10.1016/j.arr.2009.04.004.
146. Singh P.K., Doley J., Kumar G.R., Sahoo A.P., Tiwari A.K. Oncolytic viruses & their specific targeting to tumour cells. Indian J. Med. Res. 2012, 136:571-584.
147. Starkov A.A. Measurement of mitochondrial ROS production. Methods Mol. Biol. 2010, 648:245-255. 10.1007/978-1-60761-756-3_16.
148. Sud M., Fahy E., Cotter D., Brown A., Dennis E.A., Glass C.K., Merrill A.H., Murphy R.C., Raetz C.R.H., Russell D.W., Subramaniam S. LMSD: LIPID MAPS structure database. Nucleic Acids Res. 2007, 35:D527-D532. 10.1093/nar/gkl838.
149. Suresh S., Spatz J., Mills J.P., Micoulet A., Dao M., Lim C.T., Beil M., Seufferlein T. Connections between single-cell biomechanics and human disease states: gastrointestinal cancer and malaria. Acta Biomater. 2005, 1:15-30. 10.1016/j.actbio.2004.09.001.
150. Suresh S. Biomechanics and biophysics of cancer cells. Acta Biomater. 2007, 3:413-438. 10.1016/j.actbio.2007.04.002.
151. Takai H., Smogorzewska A., de Lange T. DNA damage foci at dysfunctional telomeres. Curr. Biol. 2003, 13:1549-1556. 10.1016/S0960-9822(03)00542-6.
152. Tominaga K. The emerging role of senescent cells in tissue homeostasis and pathophysiology. Pathobiol. Aging Age Relat. Dis. 2015, 5:27743.
153. Torres C.A., Perez V.I. Proteasome modulates mitochondrial function during cellular senescence. Free Radic. Biol. Med. 2008, 44:403-414. 10.1016/j.freeradbiomed.2007.10.002.
154. Toussaint O., Medrano E.E., von Zglinicki T. Cellular and molecular mechanisms of stress-induced premature senescence (SIPS) of human diploid fibroblasts and melanocytes. Exp. Gerontol. 2000, 35:927-945.
155. Urruticoechea A., Smith I.E., Dowsett M. Proliferation marker Ki-67 in early breast cancer. J. Clin. Oncol. 2005, 23:7212-7220. 10.1200/JCO.2005.07.501.
156. Vandenberk B., Brouwers B., Hatse S., Wildiers H. p16INK4a: a central player in cellular senescence and a promising aging biomarker in elderly cancer patients. J. Geriatr. Oncol. 2011, 2:259-269. 10.1016/j.jgo.2011.08.004.
157. Verheije M.H., Rottier P.J.M. Retargeting of viruses to generate oncolytic agents. Adv. Virol. 2012, 798526. 10.1155/2012/798526.
158. Voutetakis K., Chatziioannou A., Gonos E.S., Trougakos I.P. Comparative meta-Analysis of transcriptomics data during cellular senescence and In vivo tissue ageing. Oxid. Med. Cell. Longev. 2015, 2015:1-17. 10.1155/2015/732914.
159. Wang J.C., Bennett M. Aging and atherosclerosis: mechanisms functional consequences, and potential therapeutics for cellular senescence. Circ. Res. 2012, 111:245-259. 10.1161/CIRCRESAHA.111.261388.
160. Wang X., Su C., Cao H., Li K., Chen J., Jiang L., Zhang Q., Wu X., Jia X., Liu Y., Wang W., Liu X., Wu M., Qian Q. A novel triple-regulated oncolytic adenovirus carrying p53 gene exerts potent antitumor efficacy on common human solid cancers. Mol. Cancer Ther. 2008, 7:1598-1603. 10.1158/1535-7163.MCT-07-2429.
161. Wang C., Jurk D., Maddick M., Nelson G., Martin-Ruiz C., von Zglinicki T. DNA damage response and cellular senescence in tissues of aging mice. Aging Cell 2009, 8:311-323. 10.1111/j.1474-9726.2009.00481.x.
162. Wang F., Pan X., Kalmbach K., Seth-Smith M.L., Ye X., Antumes D.M.F., Yin Y., Liu L., Keefe D.L., Weissman S.M. Robust measurement of telomere length in single cells. Proc. Natl. Acad. Sci. U. S. A. 2013, 110:E1906-E1912. 10.1073/pnas.1306639110.
163. Webley K., Bond J.A., Jones C.J., Blaydes J.P., Craig A., Hupp T., Wynford-Thomas D. Posttranslational modifications of p53 in replicative senescence overlapping but distinct from those induced by DNA damage. Mol. Cell. Biol. 2000.
164. Wei Y.H., Ma Y.S., Lee H.C., Lee C.F., Lu C.Y. Mitochondrial theory of aging matures-roles of mtDNA mutation and oxidative stress in human aging. Zhonghua Yi Xue Za Zhi (Taipei) 2001, 64:259-270.
165. Willoughby N.A., Bock H., Hoeve M.A., Pells S., Williams C., McPhee G., Freile P., Choudhury D., De Sousa P.A. A scalable label-free approach to separate human pluripotent cells from differentiated derivatives. Biomicrofluidics 2016, 10:014107. 10.1063/1.4939946.
166. Wimo A., Jönsson L., Bond J., Prince M., Winblad B. The worldwide economic impact of dementia 2010. Alzheimers Dement. 2013, 9(1-11):e3. 10.1016/j.jalz.2012.11.006.
167. Wu B., Ueno M., Onodera M., Kusaka T., Huang C., Hosomi N., Kanenishi K., Sakamoto H. Age-related changes in P-glycoprotein expression in senescence-accelerated mouse. Curr. Aging Sci. 2009, 2:187-192.
168. Yang N.-C., Hu M.-L. The limitations and validities of senescence associated-beta-galactosidase activity as an aging marker for human foreskin fibroblast Hs68 cells. Exp. Gerontol. 2005, 40:813-819. 10.1016/j.exger.2005.07.011.
169. Zacarias-Fluck M.F., Morancho B., Vicario R., Luque Garcia A., Escorihuela M., Villanueva J., Rubio I.T., Arribas J. Effect of cellular senescence on the growth of HER2-positive breast cancers. J. Natl. Cancer Inst. 2015, 107. 10.1093/jnci/djv020.
170. Zhu Y., Tchkonia T., Fuhrmann-Stroissnigg H., Dai H.M., Ling Y.Y., Stout M.B., Pirtskhalava T., Giorgadze N., Johnson K.O., Giles C.B., Wren J.D., Niedernhofer L.J., Robbins P.D., Kirkland J.L. Identification of a novel senolytic agent, navitoclax, targeting the bcl-2 family of anti-apoptotic factors. Aging Cell 2015, 10.1111/acel.12445.
171. Zhu Y., Tchkonia T., Pirtskhalava T., Gower A.C., Ding H., Giorgadze N., Palmer A.K., Ikeno Y., Hubbard G.B., Lenburg M., O' S.P., Hara, LaRusso N.F., Miller J.D., Roos C.M., Verzosa G.C., LeBrasseur N.K., Wren J.D., Farr J.N., Khosla S., Stout M.B., McGowan S.J., Fuhrmann-Stroissnigg H., Gurkar A.U., Zhao J., Colangelo D., Dorronsoro A., Ling Y.Y., Barghouthy A.S., Navarro D.C., Sano T., Robbins P.D., Niedernhofer L.J., Kirkland J.L. The Achilles' heel of senescent cells: from transcriptome to senolytic drugs. Aging Cell 2015, 14:644-658. 10.1111/acel.12344.
172. Zietzer A., Hillmeister P. Leucocyte telomere length as marker for cardiovascular ageing. Acta Physiol. (Oxf) 2014, 211:251-256. 10.1111/apha.12284.
173. von Zglinicki T., Saretzki G., Ladhoff J., d'Adda di Fagagna F., Jackson S.P. Human cell senescence as a DNA damage response. Mech. Ageing Dev. 2005, 126:111-117. 10.1016/j.mad.2004.09.034.