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Somatic Cell and Molecular Genetics

, Volume 15, Issue 3, pp 191–202 | Cite as

In vivo aging of human fibroblasts does not alter nuclear plasticity in heterokaryons

  • Grace K. Pavlath
  • Choy -Pik Chiu
  • Helen M. Blau
Article

Abstract

In vivo aging of human fibroblasts altered proliferative properties but not the potential for novel gene expression in response to muscle trans-acting factors. Heterokaryons produced by fusing fibroblasts with muscle cells permitted a dissociation of the effects of aging on cell division and other cell functions. Skin fibroblasts derived from fetal and adult stages of development were distinct cell types based on their doubling time, protein content, cell size, and specific binding of insulin and insulin-like growth factor I. Despite these differences in growth parameters, the two cell types were indistinguishable in heterokaryons. Muscle gene activation occurred in the absence of changes in chromatin structure requiring DNA replication. In addition, the time course, maximal efficiency, and effect of gene dosage on the expression of muscle gene products were similar for heterokaryons containing fetal and adult fibroblasts but distinct for heterokaryons containing keratinocytes. The difference between fibroblasts and keratinocytes in the time course of muscle gene expression is likely to reflect mechanisms of gene activation at the transcriptional level, since the kinetics of muscle protein accumulation paralleled that of muscle transcripts. These results indicate that nuclear plasticity is not altered in fibroblasts by in vivo aging.

Keywords

Gene Activation Doubling Time Chromatin Structure Human Fibroblast Muscle Protein 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Literature cited

  1. 1.
    Hayflick, L., and Moorhead, M.S. (1961).Exp. Cell Res. 25:585–621.Google Scholar
  2. 2.
    Hayflick, L. (1965).Exp. Cell Res. 37:614–636.PubMedGoogle Scholar
  3. 3.
    Martin, G.M., Sprague, C.A., and Epstein, C.J. (1970).Lab Invest. 23:86–92.PubMedGoogle Scholar
  4. 4.
    LeGuilly, Y., Simon, M., Lenoir, P., and Bourel, M. (1973).Gerontology 19:303–313.Google Scholar
  5. 5.
    Tice, R.R., Schneider, E.L., Kram, D., and Thorne, P. (1979).J. Exp. Med. 149:1029–1041.PubMedGoogle Scholar
  6. 6.
    Cristafalo, V.J., Stanulis-Praeger, B.M. (1982). InAdvances in Cell Culture, Vol. 2. (ed.) Maramorosch, K. (Academic Press) New York, pp. 1–68.Google Scholar
  7. 7.
    Stanulis-Praeger, B.M. (1987).Mech. Aging Dev. 38:1–48.PubMedGoogle Scholar
  8. 8.
    Orgel, L.E. (1963).Proc. Natl. Acad. Sci. U.S.A. 49:517–521.PubMedGoogle Scholar
  9. 9.
    Orgel, L.E. (1973).Nature 243:441–445.PubMedGoogle Scholar
  10. 10.
    Crowley, C., and Curtis, H.J. (1963).Proc. Natl. Acad. Sci. U.S.A. 49:626–628.Google Scholar
  11. 11.
    Harman, D. (1981).Proc. Natl. Acad. Sci. U.S.A. 78:7124–7128.PubMedGoogle Scholar
  12. 12.
    Linn, S., Kairis, M., and Holliday, R. (1976).Proc. Natl. Acad. Sci. U.S.A. 23:2818–2822.Google Scholar
  13. 13.
    Schmookler-Reis, R.J., and Goldstein, S. (1980).Cell 21:739–749.PubMedGoogle Scholar
  14. 14.
    Murray, V., and Holliday, R. (1981).J. Mol. Biol. 146:55–76.PubMedGoogle Scholar
  15. 15.
    Martin, G.M., Smith, A.C., Ketterer, D.J., Ogburn, C.E., and Disteche, C.M. (1985).Isr. J. Med. Sci. 21:296–301.PubMedGoogle Scholar
  16. 16.
    Martin, G.M., Sprague, C.A., Norwood, T.H., and Pendergrass, W.R. (1974).Am. J. Pathol. 74:137–153.PubMedGoogle Scholar
  17. 17.
    Bell, E., Marek, L.F., Merrill, C., Levinstone, D.S., Young, I.T., Eden, M., and Sher, S. (1978).Science 202:1158–1163.PubMedGoogle Scholar
  18. 18.
    Hoehn, H., Bryant, E.M., and Martin, G.M. (1978).Cytogenet. Cell Genet. 21:282–295.PubMedGoogle Scholar
  19. 19.
    Pereira-Smith, O.M., and Smith, J.R. (1982).Somat. Cell Genet. 8:731–742.PubMedGoogle Scholar
  20. 20.
    Burmer, G.C., Zeigler, C.J. and Norwood, T.H. (1982).J. Cell Biol. 94:187–192.PubMedGoogle Scholar
  21. 21.
    Burmer, G.C., Motulsky, H., Zeigler, C.J., and Norwood, T.H. (1983).Exp. Cell Res. 145:79–84.PubMedGoogle Scholar
  22. 22.
    Drescher-Lincoln, C.K., and Smith, J.R. (1983).Exp. Cell Res. 144:455–462.PubMedGoogle Scholar
  23. 23.
    Lumpkin, C.K., Jr., McClung, J.K., Pereira-Smith, O.M., and Smith, J.R. (1986).Science 232:393–395.PubMedGoogle Scholar
  24. 24.
    Blau, H.M., Chiu, C.-P., and Webster, C. (1983).Cell 32:1171–1180.PubMedGoogle Scholar
  25. 25.
    Chiu, C.-P. and Blau, H.M. (1984).Cell 37:879–887.PubMedGoogle Scholar
  26. 26.
    Chiu, C.-P. and Blau, H.M. (1985).Cell 40:417–424.PubMedGoogle Scholar
  27. 27.
    Miller, S.C., Pavlath, G.K., Blakely, B.T., and Blau, H.M. (1988).Genes Dev 2:330–340.PubMedGoogle Scholar
  28. 28.
    Blau, H.M., Pavlath, G.K., Hardeman, E.C., Chiu, C-P., Silberstein, L., Webster, S.G., Miller, S.C., and Webster, C. (1985).Science 230:758–766.PubMedGoogle Scholar
  29. 29.
    Bradford, M.M. (1976).Anal. Biochem. 72:248–254.PubMedGoogle Scholar
  30. 30.
    Roth, R.A., Maddux, B., Wong, K.Y., Styne, D.M., Van Vliet, G., Humbel, R.E., and Goldfine, I. (1983).Endocrinology 112:1865–1867.PubMedGoogle Scholar
  31. 31.
    Shimizu, M., Webster, C., Morgan, D.O., Blau, H.M., and Roth, R.A. (1986).Am J. Physiol. 251:E611-E615.PubMedGoogle Scholar
  32. 32.
    Rheinwald, J.G., and Green, H. (1977).Nature 265:421–424.PubMedGoogle Scholar
  33. 33.
    Rheinwald, J.G., and Green, H. (1975).Cell 6:331–344.PubMedGoogle Scholar
  34. 34.
    Gilfix, B.M., and Green, H. (1984).J. Cell Physiol. 119:172–174.PubMedGoogle Scholar
  35. 35.
    Sun, T.-T., and Green, H. (1978).Cell 14:469–476.PubMedGoogle Scholar
  36. 36.
    Yaffe, D., and Saxel, O. (1977).Nature 270:725–727.PubMedGoogle Scholar
  37. 37.
    Thompson, L.H., and Baker, R.M. (1973). InMethods in Cell Physiology, (ed.) Prescott, D.M. (Academic Press) New York, pp. 209–281.Google Scholar
  38. 38.
    Pavlath, G.K., and Blau, H.M. (1986).J. Cell Biol. 102:124–130.PubMedGoogle Scholar
  39. 39.
    Hardeman, E.C., Chiu, C.-P., Minty, A., and Blau, H.M. (1986).Cell 47:123–130.PubMedGoogle Scholar
  40. 40.
    Strohman, R.C., Moss, P.S., Micou-Eastwood, J., Spector, D., Przybyla, A., and Paterson, B. (1977).Cell 10:265–273.PubMedGoogle Scholar
  41. 41.
    Gunning, P., Ponte, P., Blau, H., and Kedes, L. (1983).Mol. Cell. Biol. 3:1985–1995.PubMedGoogle Scholar
  42. 42.
    Gunning, P., Ponte, P., Okayama, H., Engel, J., Blau, H., and Kedes, L. (1983).Mol. Cell. Biol. 3:787–795.PubMedGoogle Scholar
  43. 43.
    Gunning, P., Mohun, T., Ng, S.-Y., Ponte, P. and Kedes, L. (1984).J. Mol. Evol. 20:202–214.PubMedGoogle Scholar
  44. 44.
    Rosenbloom, A.L., Goldstein, S., and Yip, C.C. (1976).Science 193:412–415.Google Scholar
  45. 45.
    Schneider, E.L., and Mitsui, Y. (1976).Proc. Natl. Acad. Sci. U.S.A. 73:3584–3588.PubMedGoogle Scholar
  46. 46.
    Conover, C.A., Rosenfeld, R.G., and Hintz, R.L. (1987).J. Gerontol. 42:308–314.PubMedGoogle Scholar
  47. 47.
    Bains, W., Ponte, P., Blau, H., and Kedes, L. (1984).Mol. Cell. Biol. 4:1449–1453.PubMedGoogle Scholar
  48. 48.
    Barrandon, Y., and Green, H. (1985).Proc. Natl. Acad. Sci. U.S.A. 82:5390–5394.PubMedGoogle Scholar
  49. 49.
    Taylor, S.M., and Jones, P.A. (1982).J. Cell. Physiol. 111:187–194.PubMedGoogle Scholar
  50. 50.
    Wilson, V.L., and Jones, P.A. (1983).Science 220:1055–1057.PubMedGoogle Scholar
  51. 51.
    Brown, D.B. (1984).Cell 37:359–365.PubMedGoogle Scholar
  52. 52.
    Weintraub, H. (1985).Cell 42:705–774.PubMedGoogle Scholar
  53. 53.
    Forrester, W.C., Takegawa, S., Papayannopoulou, T., Stamatoyannopoulos, G., and Groudine, M. (1987).Nucleic Acids Res. 15:10159–10177.PubMedGoogle Scholar
  54. 54.
    Kull, F.C., Jr., Jacobs, S., Su, Y.-F., Svoboda, M.E., Van Wyck, J.J., and Cuatrecasas, P. (1983).J. Biol. Chem. 258:6561–6566.PubMedGoogle Scholar
  55. 55.
    Morgan, D.O., Jarnagin, K., and Roth, R.A. (1986).Biochemistry 25:5560–5564.PubMedGoogle Scholar
  56. 56.
    Webster, C., Pavlath, G.K., Parks, D.R., Walsh, F.S., and Blau, H.M. (1988).Exp. Cell Res. 174:252–265.PubMedGoogle Scholar
  57. 57.
    Flier, J.S., Usher, P., and Moses, A.C. (1986).Proc. Natl. Acad. Sci. U.S.A. 83:664.PubMedGoogle Scholar
  58. 58.
    Furlanetto, R.W., DiCarlo, J.N., and Wisehart, C. (1987).J. Clin. Endocrinol. Metab. 64:1142–1149.PubMedGoogle Scholar
  59. 59.
    Holliday, R., and Tarrant, G.M. (1972).Nature 238:26–30.PubMedGoogle Scholar
  60. 60.
    Hoehn, H., Bryant, E.M., Au, K., Norwood, T.H., Boman, H., and Martin, G.M. (1975).Cytogenet. Cell Genet. 15:282–298.PubMedGoogle Scholar
  61. 61.
    Hayflick, L. (1973).Am. J. Med. Sci. 265:432–445.PubMedGoogle Scholar
  62. 62.
    Martin, G.M., Hoehn, H., and Bryant, E.M. (1980).Adv. Exp. Med. Biol. 129:139–145.PubMedGoogle Scholar
  63. 63.
    Pereira-Smith, O.M., and Smith, J.R. (1983).Science 221:964–966.PubMedGoogle Scholar
  64. 64.
    Drescher-Lincoln, C.K., and Smith, J.R. (1984).Exp. Cell Res. 153:208–217.PubMedGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1989

Authors and Affiliations

  • Grace K. Pavlath
    • 1
  • Choy -Pik Chiu
    • 1
  • Helen M. Blau
    • 1
  1. 1.Department of PharmacologyStanford University School of MedicineStanford

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