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Cellular aging in vitro

Published online by Cambridge University Press:  17 November 2008

Matthew D Gray
Affiliation:
University of Washington, Seattle, Washington, USA
Thomas H Norwood*
Affiliation:
University of Washington, Seattle, Washington, USA
*
Thomas H Norwood, Professor of Pathology, Department of Pathology, University of Washington, School of Medicine, Box 357470, Seattle, WA 98195–7470, USA.

Abstract

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Type
Biological gerontology
Copyright
Copyright © Cambridge University Press 1995

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References

1Harrison, RE. Observations on the living developing nerve fiber. Proc Soc Exp Biol 1907; 4: 140–43.CrossRefGoogle Scholar
2Hayflick, L. The limited in vitro lifetime of human diploid cell strains. Exp Cell Res 1965; 37: 614–36.CrossRefGoogle ScholarPubMed
3Hayflick, L, Moorhead, PS. The serial cultivation of human diploid cell strains. Exp Cell Res 1961; 25: 585621.CrossRefGoogle ScholarPubMed
4Martin, GM, Sprague, CA, Epstein, CJ. Replicative life-span of cultivated human cells. Effects of donor's age, tissue, and genotype. Lab Invest 1970; 23: 8692.Google ScholarPubMed
5Goldstein, S. Lifespan of cultured cells in progeria. Lancet 1969; i: 424.CrossRefGoogle Scholar
6Martin, GM. Genetic syndromes in man with potential relevance to the pathobiology of aging. Birth Defects 1978; 14: 539.Google Scholar
7Goldstein, S. Human genetic disorders that feature premature onset and accelerated progression of biological aging. In: Schneider, EL ed. The genetics of aging. New York: Plenum Press, 1978: 171224.CrossRefGoogle Scholar
8Daniel, CW. Cell longevity in vivo. In: Hayflick, L, Finch, CE eds. Handbook of the biology of aging. New York: Van Nostrand Reinhold, 1977: 122–58.Google Scholar
9Daniel, CW, Young, LJ. Influence of cell division on an aging process. Life span of mouse mammary epithelium during serial propagation in vivo. Exp Cell Res 1971; 65: 2732.CrossRefGoogle Scholar
10Daniel, CW. DeOme, KB, Young, JT, Blair, PB, Faulken, LJ. The in vivo life span of normal and preneoplastic mouse mammary glands: a serial transplantation study. Proc Natl Acad Sci USA 1968; 61: 5260.CrossRefGoogle ScholarPubMed
11Norwood, TH, Smith, JR, Stein, GH. Aging at the cellular level: the human fibroblast cell model. In: Schneider, EL, Rowe, JW eds. Handbook of the biology of aging. New York: Academic Press, 1990: 131–54.Google Scholar
12Harrison, DE. Cell and tissue transplantation: a means of studying the aging process. In: Finch, CE, Schneider, EL eds. Handbook of the biology of aging, second edition. New York: Van Nostrand Reinhold, 1985: 322–56.Google Scholar
13Kohn, RR. Aging and cell division. Science 1975; 188: 203204.CrossRefGoogle ScholarPubMed
14Norwood, TH. Cellular aging. In: Cassel, CK, Riesenberg, DE, Sorensen, LB, Walsh, JR eds. Geriatric medicine, second edition. New York/Berlin: Springer-Verlag, 1990: 115.Google Scholar
15Martin, GM, Ogburn, CE, Sprague, CA. Senescence and vascular disease. In: Cristofalo, VJ, Roberts, J, Adelman, RC eds. Explorations in aging. New York: Plenum Press, 1975: 163–93.CrossRefGoogle Scholar
16Gey, GO, Coffman, WD, Kubicek, M. Tissue culture studies of the proliferative capacity of cervical carcinoma and normal epithelium. Cancer Res 1952; 12: 264–65.Google Scholar
17McCormick, JJ, Maher, VM. Towards an understanding of the malignant transformation of diploid human fibroblasts. Mutat Res 1988; 199: 273–91.CrossRefGoogle ScholarPubMed
18Rhim, JS. Neoplastic transformation of human cells in vitro. Crit Rev Oncogenesis 1993; 4: 313–35.Google ScholarPubMed
19Mukherji, B, MacAlister, TJ, Guha, A, Gillies, CG, Jeffers, DC, Slocum, SK. Spontaneous in vitro transformation of human fibroblasts. J Natl Cancer Inst 1984; 73: 583–93.Google ScholarPubMed
20Bischoff, FZ, Yin, SZ, Palhak, S et al. Spontaneous abnormalities in normal fibroblasts from patients with Li-Fraumeni syndrome: aneuploidy and immortalization. Cancer Res 1990; 50: 7979–84.Google ScholarPubMed
21Malkin, D, Li, FP, Strong, LC et al. Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science 1990; 250: 1233–38.CrossRefGoogle Scholar
22Croce, CM, Koprowski, H. Somatic cell hybrids between mouse peritoneal macrophages and SV40 transformed human cells. I. Positive control of the transformed phenotypes by the human chromosome 7 carrying the SV40 genome. J Exp Med 1974; 140: 1221–29.CrossRefGoogle ScholarPubMed
23Mayne, LV, Priestley, A, James, MR, Burke, JF. Efficient immortalization and morphological transformation of human fibroblasts by transfection with SV40 DNA linked to a dominant marker. Exp Cell Res 1986; 162: 530–38.CrossRefGoogle ScholarPubMed
24Namba, M, Nishitani, K, Hyodoh, F, Fukushima, F, Kimoto, T. Neoplastic transformation of human diploid fibroblasts (KMST-6) by treatment with 60Co gamma rays. Int J Cancer 1985; 35: 275–80.CrossRefGoogle ScholarPubMed
25Curatolo, L, Erba, E, Moresca, L. Culture conditions induce the appearance of immortalized C2H mouse cell lines. In Vitro 1984; 28: 597601.CrossRefGoogle Scholar
26Todaro, G, Green, H. Quantitative growth of mouse embryo cells in culture and their development into established lines. J Cell Biol 1963; 17: 299313.CrossRefGoogle ScholarPubMed
27Macieira-Coehlo, A, Azzarone, B. The transition from primary culture to spontaneous immortalization in mouse fibroblast populations. Anticancer Res 1988; 8: 669–76.Google Scholar
28Mondal, S, Heidelberger, C. Transformation of C3H/10T1/2C18 mouse embryo fibroblasts by ultraviolet radiation and phorbol ester. Nature 1977; 260: 710–11.CrossRefGoogle Scholar
29Macieira-Coehlo, A. Cancer and aging at the cellular level. In: Macieira-Coehlo, A, Nordenskjold, B eds. Cancer and aging. Boca Raton, FL: CRC Press, 1990: 1137.Google Scholar
30Sager, R. Tumor suppressor genes: the puzzle and the promise. Science 1989; 246: 1406–12.CrossRefGoogle ScholarPubMed
31Bell, E, Marek, LF, Levinstone, DS et al. Loss of division potential in vitro: aging or differentiation? Departure of cells from cycle may not be a sign of aging, but a sign of differentiation. Science 1978; 202: 1158–63.CrossRefGoogle ScholarPubMed
32Altman, PS, Dittmer, DS eds. Lifespan: mammals. In: Growth including reproduction and morphological development. Washington, DC: Federation of American Societies for Experimental Biology, 1962: 445–50.Google Scholar
33Orgel, LE. The maintenance of the accuracy of protein synthesis and its relevance to ageing. Proc Natl Acad Sci USA 1963; 49: 517–21.CrossRefGoogle ScholarPubMed
34Orgel, LE. The maintenance of the accuracy of protein synthesis and its relevance to ageing: a correction. Proc Natl Acad Sci USA 1970; 67: 1476.CrossRefGoogle ScholarPubMed
35Harmon, D. The free radical theory of aging. In: Warner, HR, Butler, RN, Sprott, RL, Schneider, EL eds. Modern biological theories of aging. New York: Raven Press, 1987: 8187.Google Scholar
36Ames, BN, Shigenaga, MK. Oxidants are a major contributor to aging. Ann NY Acad Sci 1992; 663: 8596.CrossRefGoogle Scholar
37Chen, Q, Ames, BN. Senescence-like growth arrest induced by hydrogen peroxide in human diploid fibroblast F65 cells. Proc Natl Acad Sci USA 1994; 91: 4130–34.CrossRefGoogle ScholarPubMed
38Rohme, D. Evidence for a relationship between longevity of mammalian species and life-spans of normal fibroblasts in vitro and erythrocytes in vivo. Proc Natl Acad Sci USA 1981; 78: 5009–13.CrossRefGoogle ScholarPubMed
39Norwood, TH, Pendergrass, WR, Sprague, CA, Martin, GM. Dominance of the senescent phenotypes in heterokaryons between replicative and post-replicative human fibroblast-like cells. Proc Natl Acad Sci USA 1974; 73: 2223–36.Google Scholar
40Pereira-Smith, OM, Smith, JR. The phenotype of low proliferative potential is dominant in hybrids of normal human fibroblasts. Somat Cell Genet 1982; 6: 731–42.CrossRefGoogle Scholar
41Pereira-Smith, OM, Smith, JR. Evidence for the recessive nature of cellular immortality. Science 1983; 221: 964–66.CrossRefGoogle ScholarPubMed
42Stein, GH, Yanishevsky, RM, Gordon, L, Beeson, M. Carcinogen-transformed human cells are inhibited from entry into S phase by fusion to senescent cells but cells transformed by DNA tumor viruses overcome the inhibition. Proc Natl Acad Sci USA 1982; 79: 5287–91.CrossRefGoogle ScholarPubMed
43Pereira-Smith, OM, Smith, JR. Genetic analysis of indefinite division in human cells. Identification of four complementation groups. Proc Natl Acad Sci USA 1988; 85: 6042–46.CrossRefGoogle ScholarPubMed
44Duncan, EL, Whitaker, NJ, Moy, EL, Reddel, RR. Assignment of SV40-immortalized cells to more than one complementation group for immortalization. Exp Cell Res 1993; 205: 337–44.CrossRefGoogle Scholar
45Ryan, PA, Maher, VM, McCormick, JJ. Failure of infinite life span cells from different immortality complementation group to yield finite life span hybrids. J Cell Physiol 1994; 159: 151–60.CrossRefGoogle ScholarPubMed
46Sugawara, O, Shimura, M, Koi, M, Annab, LA, Barrett, JC. Induction of cellular senescence in immortalized cells by human chromosome 1. Science 1990; 247: 707–10.CrossRefGoogle ScholarPubMed
47Ning, Y, Weber, JL, Killary, AM, Ledbetter, DH, Smith, JR, Pereira-Smith, OM. Genetic analysis of indefinite division in human cells: evidence for a cell senescence-related gene(s) on human chromosome 4. Proc Natl Acad Sci USA 1991; 88: 5635–39.CrossRefGoogle ScholarPubMed
48Collins, FS. Positional cloning moves from perditional to traditional. Nature Genet 1995; 9: 347–50.CrossRefGoogle ScholarPubMed
49Noda, A, Ning, Y, Venable, SF, Pereira-Smith, OM, Smith, JR. Cloning of senescent cell-derived inhibitors of DNA synthesis using an expression screen. Exp Cell Res 1994; 211: 9098.CrossRefGoogle ScholarPubMed
50Morgan, DO. Principles of CDK regulation. Nature 1995; 374: 131–34.CrossRefGoogle ScholarPubMed
51Pines, J. The cell cycle kinases. Semin Cancer Biol 1994; 5: 305–13.Google ScholarPubMed
52Sherr, CJ. Mammalian G1 cyclins. Cell 1993; 73: 1059–65.CrossRefGoogle ScholarPubMed
53Koff, A, Giordano, A, Desai, D et al. Formation and activation of a cyclin E-cdk2 complex during the G1 phase of the human cell cycle. Science 1992; 257: 1689–94.CrossRefGoogle ScholarPubMed
54Ohtsubo, M, Roberts, JM. Cyclin-dependent regulation of G1 in mammalian fibroblasts. Science 1993; 259: 1908–12.CrossRefGoogle ScholarPubMed
55Harper, JW, Adami, GR, Wei, N, Keyomarsi, K, Elledge, SJ. The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. Cell 1993; 75: 805–16.CrossRefGoogle ScholarPubMed
56El-Deiry, WS, Tokino, T, Velculescu, VE et al. WAF1, a potential mediator of p53 tumor suppression. Cell 1993; 75: 817–25.CrossRefGoogle ScholarPubMed
57Xiong, Y, Hannon, GJ, Zhang, H, Casso, D, Kobayashi, R, Beach, D. p21 is a universal inhibitor of cyclin kinases. Nature 1993; 366: 701704.CrossRefGoogle ScholarPubMed
58Gu, Y, Turck, CW, Morgan, DO. Inhibition of CDK2 activity in vivo by an associated 20K regulatory subunit. Nature 1993; 366: 707–10.CrossRefGoogle ScholarPubMed
59Rabinovitch, PS, Norwood, TH. Comparative heterokaryon study of cellular senescence and the serum-derived state. Exp Cell Res 1980; 130: 101109.CrossRefGoogle Scholar
60Schneider, EL, Fowlkes, BJ. Measurement of DNA content and cell volume in senescent human fibroblasts utilizing flow multiparameter single cell analysis. Exp Cell Res 1976; 98: 298302.CrossRefGoogle ScholarPubMed
61Yanishevsky, R, Mendelsohn, ML, Mayall, BH, Cristofalo, VJ. Proliferative capacity and DNA content of aging human diploid cells in culture: a cytophotometric and autoradiographic analysis. J Cell Physiol 1974; 84: 165–70.CrossRefGoogle ScholarPubMed
62Peter, M, Herskowitz, I. Joining the complex: cyclin-dependent kinase inhibitory proteins and the cell cycle. Cell 1994; 79: 181–84.CrossRefGoogle ScholarPubMed
63Halevy, O, Novitch, BG, Spicer, DB et al. Correlation of terminal cell cycle arrest of skeletal muscle with induction of p21 by MyoD. Science 1995; 267: 1018–21.CrossRefGoogle ScholarPubMed
64Parker, SB, Eichele, G, Zhang, P et al. p53-Independent expression of p21ciP1 in muscle and other terminally differentiating cells. Science 1995; 267: 1024–27.CrossRefGoogle ScholarPubMed
65Di Leonardo, A, Linke, SP, Clarkin, K, Wahl, GM. DNA damage triggers a prolonged p53-dependent G1 arrest and long-term induction of Cipl in normal human fibroblasts. Gene Dev 1994; 8: 2540–51.CrossRefGoogle Scholar
66El-Deiry, WS, Harper, JW, O'Connor, PM et al. WAF1/CIP1 is induced in p53-mediated G1 arrest and apoptosis. Cancer Res 1994; 54: 1169–74.Google Scholar
67Kastan, MB, Onyekwere, O, Sidransky, D, Vogelstein, B, Craig, RW. Participation of p53 protein in the cellular response to DNA damage. Cancer Res 1991; 51: 6304–11.Google ScholarPubMed
68Kastan, MB, Zhan, Q, El-Deiry, WS et al. A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia. Cell 1992; 71: 587–97.CrossRefGoogle ScholarPubMed
69Weinberg, RA. Positive and negative controls on cell growth. Biochemistry 1989; 28: 8263–69.CrossRefGoogle ScholarPubMed
70Miller, C, Koeffler, HP. p53 mutations in human cancer. Leukemia 1993; 7: 1821.Google ScholarPubMed
71Weinberg, RA. The retinoblastoma gene and gene product. Cancer Surv 1992; 12: 4357.Google ScholarPubMed
72Huang, HJ, Yee, JK, Show, JY et al. Suppression of the neoplastic phenotype by replacement of the RB gene in human cancer cells. Science 1988; 242: 1563–66.CrossRefGoogle ScholarPubMed
73Casey, G, Lo-Hsueh, M, Lopez, ME, Vogelstein, B, Stanbridge, EJ. Growth suppression of human breast cancer cells by introduction of a wild-type p63 gene. Oncogene 1991; 6: 1791–97.Google Scholar
74Goodrich, DW, Wang, NP, Qian, Y-W, Lee, EY-HP, Lee, W-H. The retinoblastoma gene product regulates progression through G1 phase of the cell cycle. Cell 1991; 67: 293302.CrossRefGoogle ScholarPubMed
75Chen, PL, Scully, P, Shew, JY, Wang, JY, Lee, WH. Phosphorylation of the retinoblastoma gene product is modulated during the cell cycle and cellular differentiation. Cell 1989; 58: 1193–98.CrossRefGoogle ScholarPubMed
76Hinds, PW, Mittnacht, S, Dulic, V, Arnold, A, Need, SI, Wainberg, RA. Regulation of retinoblastoma protein functions by ectopine expression of human cyclins. Cell 1992; 70: 9931006.CrossRefGoogle ScholarPubMed
77Stein, GH, Beeson, M, Gordon, L. Failure to phosphorylate the retinoblastoma gene product in senescent human fibroblasts. Science 1990; 249: 666–69.CrossRefGoogle ScholarPubMed
78Stein, GH, Drullinger, LF, Robetorye, RS, Pereira-Smith, OM, Smith, JR. Senescent cells fail to express cdc2, cycA, and cycB in response to mitogen stimulation. Proc Natl Acad Sci USA 1991; 88: 11012–16.CrossRefGoogle ScholarPubMed
79Hartwell, L. Defects in a cell cycle checkpoint may be responsible for the genomic instability of cancer cells. Cell 1992; 71: 543–46.CrossRefGoogle Scholar
80Afshari, CA, Vojta, PJ, Annab, LA, Futreal, PA, Willard, TB, Barrett, JC. Investigation of the role of G1/S cell cycle mediators in cellular senescence. Exp Cell Res 1993; 209: 231–37.CrossRefGoogle ScholarPubMed
81Kulju, KS, Lehman, JM. Increased p53 protein associated with aging in human diploid fibroblasts. Exp Cell Res 1995; 217: 336–45.CrossRefGoogle ScholarPubMed
82Bond, JA, Wyllie, FS, Wynford-Thomas, D. Escape from senescence in human diploid fibroblasts induced directly by mutant p53. Oncogene 1994; 9: 1885–89.Google ScholarPubMed
83Rattan, SIS. DNA damage and repair during cellular aging. Int Rev Cytol 1989; 116: 4788.CrossRefGoogle ScholarPubMed
84Thompson, KVA, Holliday, R. Chromosome changes during the in vitro aging of MRC-5 human fibroblasts. Exp Cell Res 1975; 96: 16.CrossRefGoogle ScholarPubMed
85Benn, PA. Specific chromosome aberrations in senescent fibroblast cell lines derived from human embryos. Am J Hum Genet 1976; 28: 465–73.Google ScholarPubMed
86Mayer, PJ, Bradley, MO, Nichols, WW. No change in DNA damage or repair of single- and double-strand breaks as human diploid fibroblasts age in vitro. Exp Cell Res 1986; 166: 497509.CrossRefGoogle ScholarPubMed
87Icard, C, Beaupain, R. Spontaneous structural changes in DNA during fibroblast aging and the establishment process in vitro. Mech Ageing Dev 1980; 14: 8187.CrossRefGoogle ScholarPubMed
88Gupta, RS. Senescence of cultured human diploid fibroblasts. Are mutations responsible? J Cell Physiol 1980; 103: 209–16.CrossRefGoogle ScholarPubMed
89Fulder, SJ, Holliday, R. A rapid rise in cell variants during the senescence of populations of human fibroblasts. Cell 1975; 6: 6773.CrossRefGoogle ScholarPubMed
90Goldstein, S. The role of DNA repair in aging of cultured fibroblasts from xeroderma pigmentosum and normals (35655). Proc Soc Exp Biol Med 1971; 137: 730–34.CrossRefGoogle Scholar
91Hart, RW, Setlow, RB. DNA repair in late-passage human cells. Mech Ageing Dev 1976; 5: 6777.CrossRefGoogle ScholarPubMed
92Cristofalo, VJ, Stanulis-Praeger, BM. Cellular senescence in vitro. Adv Cell Culture 1982; 2: 168.CrossRefGoogle Scholar
93Harley, CB, Futcher, AB, Greider, CW. Telomeres shorten during ageing of human fibroblasts. Nature 1990; 345: 458–60.CrossRefGoogle ScholarPubMed
94Harley, CB. Telomere loss: mitotic clock or genetic time bomb? Mutat Res 1991; 256: 271–82.CrossRefGoogle ScholarPubMed
95Greider, CW, Blackburn, EH. A telomeric sequence in the RNA of Tetrahymena telomerase required for telomere repeat synthesis. Nature 1989; 337: 331–37.CrossRefGoogle ScholarPubMed
96Yu, G-L, Bradley, JD, Altardi, LD, Blackburn, EH. In vivo alteration of telomere sequences and senescence caused by mutated Tetrahymena telomerase RNAs. Nature 1990; 334: 126–32.CrossRefGoogle Scholar
97Kim, NW, Piatyszek, MA, Prowse, KR et al. Specific association of human telomerase activity with immortal cells and cancer. Science 1994; 266: 2011–15.CrossRefGoogle ScholarPubMed
98Starling, JA, Maule, J, Hastie, ND, Allshire, R. Extensive telomere repeat arrays in mouse are hypervariable. Nucl Acid Res 1991; 18: 6881–88.CrossRefGoogle Scholar
99Dizdaroglu, M. Oxidative damage to DNA in mammalian chromatin. Mutat Res 1992; 275: 331–42.CrossRefGoogle ScholarPubMed
100Demple, B, Harrison, L. Repair of oxidative damage to DNA: enzymology and biology. Annu Rev Biochem 1994; 63: 915–48.CrossRefGoogle ScholarPubMed
101Bohr, VA, Smith, CA, Okumoto, DS, Hanawalt, PC. DNA repair in an active gene: removal of pyrimidine dimers from the DHFR gene of CHO cells is much more efficient than in the genome overall. Cell 1985; 40: 359–69.CrossRefGoogle Scholar
102Madhani, HD, Bohr, VA, Hanawalt, PC. Differential DNA reapir in transcriptionally active and inactive proto-oncogenes: c-abl and c-mos. Cell 1986; 45: 417–23.CrossRefGoogle Scholar
103Hanawalt, PC, Gee, P, Ho, L, Hsu, RK, Kane, CJM. Genomic heterogeneity of DNA repair. Ann NY Acad Sci 1992; 663: 1725.CrossRefGoogle ScholarPubMed
104Hanawalt, PC. Transcription-coupled repair and human disease. Science 1994; 266: 1957–58.CrossRefGoogle ScholarPubMed
105Weirich-Schwaiger, H, Weirich, HG, Gruber, B, Schweiger, M, Hirsch-Kauffmann, M. Correlation between senescence and DNA repair in cells from young and old individuals and in premature aging syndromes. Mutat Res 1994; 316: 3748.CrossRefGoogle Scholar
106Kruk, PA, Rampino, NJ, Bohr, VA. DNA damage and repair in telomeres: relation to aging. Proc Natl Acad Sci USA 1995; 92: 258–62.CrossRefGoogle ScholarPubMed
107Yamamoto, Y, Fujiwara, Y. Abnormal regulation of uracil-DNA glycosylase induction during cell cycle and cell passage in Bloom's syndrome fibroblast. Carcinogenesis 1986; 7: 305–10.CrossRefGoogle Scholar
108Yamamoto, Y, Fujiwara, Y. Culture-age effect on uracil-DNA glycosylase activity in normal human skin fibroblasts. J Gerontol 1987; 42: 470–75.CrossRefGoogle ScholarPubMed
109Rosenberger, RF, Gounaris, E, Kolettas, E. Mechanisms responsible for the limited lifespan and immortal phenotypes in cultured mammalian cells. J Theor Biol 1991; 148: 383–92.CrossRefGoogle ScholarPubMed
110Hart, RW, Setlow, RB. Correlation between deoxyribonucleic acid excision repair and lifespan in a number of mammalian species. Proc Natl Acad Sci USA 1974; 71: 2169–73.CrossRefGoogle Scholar
111Norwood, TH, Pendergrass, W, Bornstein, P, Martin, GM. DNA synthesis of sub-lethally injured cells in heterokaryons and its relevance to clonal senescence. Exp Cell Res 1979; 119: 1521.CrossRefGoogle Scholar
112Sandell, LL, Zakian, VA. Loss of a yeast telomere: arrest, recovery, and chromosome loss. Cell 1993; 75: 729–39.CrossRefGoogle ScholarPubMed
113Wright, WE, Shay, JW. Telomere positional effects and the regulation of cellular senescence. Trends Genet 1992; 8: 193–97.CrossRefGoogle ScholarPubMed
114Wright, WE, Pereira-Smith, OM, Shay, J. Reversible cellular senescence: implications for immortalization of normal human diploid fibroblasts. Mol Cell Biol 1989; 9: 3088–92.Google ScholarPubMed
115Hayflick, L. The cellular basis for biological aging. In: Hayflick, L, Finch, CE eds. Handbook of the biology of aging. New York: Van Nostrand Reinhold, 1977: 159–86.Google Scholar
116Hefton, JM, Darlington, GJ, Casazza, BA, Weksler, ME. Immunologic studies of aging. V: Impaired proliferation of PHA-responsive human lymphocytes in culture. J Immunol 1980; 125: 1007–10.CrossRefGoogle ScholarPubMed
117Siskind, GW. Aging and the immune system. In: Warner, HR, Butler, RN, Sprott, RL eds. Modern biological theories of aging. New York: Raven Press, 1987: 235–42.Google Scholar
118Fry, M, Silber, J, Loeb, LA, Martin, GM. Delayed and reduced cell replication and diminishing levels of DNA polymerase α in regenerating liver of aging mice. J Cell Physiol 1984; 118: 225–32.CrossRefGoogle ScholarPubMed
119Linskens, MHK, Feng, J, Andrews, WH et al. Cataloging altered gene expression in young and senescent cells using enhanced differential display. Nucl Acids Res 1995; 23: 3244–51.CrossRefGoogle Scholar
120Kaminer, MS, Gilchrest, BA. Aging of the skin. In: Hazzard, WR, Bierman, EL, Blass, JP, Ettinger, WH Jr, Halter, JB eds. Principles of geriatric medicine and gerontology, third edition. New York: McGraw-Hill, 1994: 411–29.Google Scholar
121Goodman, L, Stein, GH. Basal and induced amounts of interleukin-C mRNA decline progressively with age in human fibroblasts. J Biol Chem 1994; 269: 19250–55.CrossRefGoogle ScholarPubMed
122Graeve, L, Baumann, M, Heinrich, PC. Interleukin 6 in autoimmune disease. The role of IL6 in the physiology and pathology of the immune defense. Clin Invest 1993; 71: 664–71.CrossRefGoogle ScholarPubMed
123West, MD, Smith, JR, Shay, JW, Wright, WE, Linskens, MHK. Altered expression of plasminogen activator and plasminogen activator inhibitor during cellular senescence. Exp Gerontol 1995 (in press).CrossRefGoogle Scholar
124Goldstein, S, Moerman, EJ, Fujii, S, Sobel, BE. Overexpression of plasminogen activator inhibitor type-1 in senescent fibroblasts from normal subjects and those with Werner syndrome. J Cell Physiol 1994; 161: 571–79.CrossRefGoogle ScholarPubMed
125Murano, S, Thweatt, R, Shmookler, Reis RJ, Jones, RA, Moerman, EJ, Goldstein, S. Diverse gene sequences are overexpressed in Werner syndrome fibroblasts undergoing premature replicative senescence. Mol Cell Biol 1991; 11: 3905–14.Google ScholarPubMed
126Kumar, S, Millis, AJ, Baglioni, C. Expression of interleukin 1-inducible genes and production of interleukin 1 by aging human fibroblasts. Proc Natl Acad Sci USA 1992; 89: 4683–87.CrossRefGoogle ScholarPubMed
127Millis, AJ, Sottile, J, Hoyle, M, Mann, DM, Diemer, V. Collagenase production by early and late passage cultures of human fibroblasts. Exp Gerontol 1989; 24: 559–75.CrossRefGoogle ScholarPubMed
128DiPaolo, BR, Pignolo, RJ, Cristofalo, VJ. Overexpression of the two-chain form of cathepsin B in senescent WI-38 cells. Exp Cell Res 1992; 201: 500505.CrossRefGoogle ScholarPubMed
129Zeng, G, Millis, AJ. Expression of 72-kDa gelatinase and TIMP-2 in early and late passage human fibroblasts. Exp Cell Res 1994; 213: 148–55.CrossRefGoogle ScholarPubMed
130Millis, AJ, Hoyle, M. McCue, HM, Martini, H. Differential expression of metalloproteinase and tissue inhibitor of metalloproteinase genes in aged human fibroblasts. Exp Cell Res 1992; 201: 373–79.CrossRefGoogle ScholarPubMed
131Luce, MC, Cristofalo, VJ. Reduction in heat shock gene expression correlates with increased thermosensitivity in senescent human fibroblasts. Exp Cell Res 1992; 202: 916.CrossRefGoogle ScholarPubMed
132Pignolo, RJ, Cristofalo, VJ, Rotenberg, MO. Senescent WI-38 cells fail to express EPC-1, a gene induced in young cells upon entry into the G0 state. J Biol Chem 1993; 268: 8949–57.CrossRefGoogle ScholarPubMed
133Pignolo, RJ, Rotenberg, MO, Cristofalo, VJ. Analysis of EPC-1 growth state-dependent expression, specificity, and conservation of related sequences. J Cell Physiol 1995; 162: 110–18.CrossRefGoogle ScholarPubMed
134Ferber, A, Chang, C, Sell, C et al. Failure of senescent human fibroblasts to express the insulin-like growth factor-1 gene. J Biol Chem 1993; 268: 17883–88.CrossRefGoogle ScholarPubMed