, Volume 1, Issue 2, pp 60–67 | Cite as

Review: A comparative analysis of studies of enzyme changes with age, with comments on possible sources of error

  • Heinrich F. Klefenz
  • Bert M. Zuckerman


Studies on enzyme changes during aging from rodents, nematodes and tissue culture cells have been reviewed. In the rodent and tissue culture studies, conflicting results on aging of specific enzymes have been reported from several laboratories. These works have been analyzed, with the aim of stressing the different findings and analyzing possible reasons for the discrepancies. With regard to the nematode studies, the authors suggest that the examination of the concept of general failure of protein synthesis mechanisms as a basic cause of cellular senescence requires more rigorous methods than have been utilized in previous studies.


Culture Cell Tissue Culture Protein Synthesis Comparative Analysis Culture Study 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Reiss, U., and Gershon, D.: Comparison of cytoplasmic superoxide dismutase in liver, heart and brain of aging rats and mice. Biochem. Biophys. Res. Comm., 73: 255–262, 1976.PubMedCrossRefGoogle Scholar
  2. 2.
    Kellogg, E. W., and Fridovich, I.: Superoxide dismutase in the rat and mouse as a function of age and longevity. J. Gerontol., 31: 405–408, 1976.PubMedGoogle Scholar
  3. 3.
    Reiss, U., and Gershon, D.: Rat-liver superoxide dismutase: purification and age-related modifications. Europ. J. Biochem., 63: 617–623, 1976.PubMedCrossRefGoogle Scholar
  4. 4.
    Gershon, H., and Gershon, D.: Inactive enzyme molecules in aging mice: liver aldolase. Proc. Natl. Acad. Sci, USA, 70: 909–913, 1973.PubMedCrossRefGoogle Scholar
  5. 5.
    Weber, A., Gregori, C., and Schapira, F.: Aldolase B in the liver of senescent rats. Biochemica et Biophysia Acta, 444: 810–815, 1976.Google Scholar
  6. 6.
    Gershon, H., and Gershon, D.: Altered enzymes in senescent organisms: mouse muscle aldolase. Mech. Aging Develop., 2: 33–41, 1973.CrossRefGoogle Scholar
  7. 7.
    Yagil, G.: Are Altered glucose-6-phosphate dehydrogenase molecules present in aged liver cells? Exper. Gerontol. 11: 73–78, 1976CrossRefGoogle Scholar
  8. 8.
    Wulf, J. H., and Cutler, R. G.: Altered protein hypothesis of mammalian aging processes. 1. Thermal stability of glucose-6-phosphate dehydrogenase in C57BL/6J mouse tissue. Experi. Gerontol., 10: 101–117, 1975.CrossRefGoogle Scholar
  9. 9.
    Pendergrass, W. R., Martin, G. M., and Bornstein, P.: Evidence contrary to the protein error hypothesiss for in vitro senescence. J. Cell. Physiol., 87: 3–14, 1976.PubMedCrossRefGoogle Scholar
  10. 10.
    Kahn, A., Guillouzo, A., Cottreau, D., Marie, J., Bourel, M., Bouvin, P., and Dreyfus, J. C.: Accuracy of protein synthesis and in vitro aging. Search for altered enzymes in senescent cultured cells from human livers. Gerontology, 23: 174–184, 1977.PubMedCrossRefGoogle Scholar
  11. 11.
    Cristofalo, V. J.: Metabolic aspects of aging in diploid human cells, In Aging in Cell and Tissue Culture, edited by Holecova, E., and Cristofalo, V., New York, Plenum Press, 1970.Google Scholar
  12. 12.
    Holliday, R., and Tarrant, G. M.: Altered enzymes in ageing human fibroblasts. Nature, 238: 26–30, 1972.PubMedCrossRefGoogle Scholar
  13. 13.
    Danot, M., Gershon, H., and Gershon, D.: The lack of altered enzyme molecules in “senescent” mouse embryo fibroblasts in culture. Mech. Ageing Develop., 4: 289–299, 1975.CrossRefGoogle Scholar
  14. 14.
    Rennert, O. M., and Anker, H. S.: On the incorporation of 51, 51 51-trifluoroleucine into proteins of E. coli. Biochem., 2: 471–476, 1963.CrossRefGoogle Scholar
  15. 15.
    Orgel, L. E.: Adaptation t o wide-spread disturbance of enzyme function. J. Mol. Biol., 9: 208–212, 1964.PubMedCrossRefGoogle Scholar
  16. 16.
    Helfman, P. M., and Price, P. A.: Human parotid α-amylase — a test of the error theory of aging. Exper. Gerontol. 9: 209–214, 1974.CrossRefGoogle Scholar
  17. 17.
    Stevens, C. O., and Sauberlich, H.: Proteolytic digestion rates for altered enzymes. Radiation Res., 41: 362–374, 1970.PubMedGoogle Scholar
  18. 18.
    Goldberg, A. L.: Degradation of abnormal proteins in Escherichia coli Proc. Natl. Acad. Sci., USA, 69: 422–426, 1972.PubMedCrossRefGoogle Scholar
  19. 19.
    Goldberg, A. L., and Dice, J. F.: Intracellular protein degradation in mammalian and bacterial cells. Ann. Rev. Biochem., 43: 835–869, 1974.PubMedCrossRefGoogle Scholar
  20. 20.
    Capecchi, M. R., Capecchi, N. E., Hughes, S. H., Wahl, G. M.: Selective degradation of abnormal proteins in mammalian tissue culture cells. Proc. Natl. Acad. Sci., USA, 71: 4732–4736, 1974.PubMedCrossRefGoogle Scholar
  21. 21.
    Rothstein, M.: Ageing and the alteration of enzymes: a review. Mech. Ageing Develop. 4: 325–338, 1975.CrossRefGoogle Scholar
  22. 22.
    Schlessinger, D., and Ben-Hamida, F.: Turnover of protein in Escherichia coli starving for nitrogen. Biochemica Biophysica Acta, 119: 171–182, 1966.Google Scholar
  23. 23.
    Pine, M. J.: Steady-state measurement of the turnover of amino acid in the cellular proteins of growing Escherichia coli. Existence of two kinetically distinct reactions. J. Bacteriol, 103: 207–215, 1970.PubMedGoogle Scholar
  24. 24.
    Halvorson, H.: Intracellular protein and nucleic acid turnover in resting yeast cells. Biochemica Biophysica Acta, 27: 255–266, 1958.CrossRefGoogle Scholar
  25. 25.
    Steinberg, D., and Vaughan, M.: Intracellular protein degradation in vitro. Biochemica Biophysica Acta, 19: 584–585, 1956.CrossRefGoogle Scholar
  26. 26.
    Yoshidu, A., Buetler, E., Motulsky, A. G.: Table of human glucose-6-phosphate dehydrogenase variants. 1971. In “Mendelian Inheritance in Man.” (Ed. V. McKusich), Baltimore, Johns Hopkins Univ. Press, 561A–565a.Google Scholar
  27. 27.
    Fornaini, G., Leoncini, G., Segni, P., Calabria, G. A., and Dacha, M.: Relationship between age and properties of human and rabbit glucose-6-phosphate dehydrogenase. Europ. J. Biochem., 7: 214,–222, 1969.PubMedCrossRefGoogle Scholar
  28. 28.
    Bolla, R., and Brot, N.: Age dependent changes in enzymes involved in macromolecular synthesis in Turbatrix aceti. Arch. Biochem. Biophy., 169: 227–236, 1975.CrossRefGoogle Scholar
  29. 29.
    Reitz, M. S., Jr., and Sanadi, D. R.: An aspect of translational control of protein synthesis in aging. Changes in the iso-accepting forms of tRNA in Turbatrix aceti. Exper. Gerontol., 7: 119–129, 1972.CrossRefGoogle Scholar
  30. 30.
    Wallach, A., and Gershon, D.: Altered ribosomal particles in senescent nematodes. Mech. Ageing Develop., 3: 225–234, 1974.CrossRefGoogle Scholar
  31. 31.
    Gershon, D.: Studies on aging in nematodes. 1. The nematode as a model organism for aging research. Exper. Gerontol., 5: 7–12, 1974.CrossRefGoogle Scholar
  32. 32.
    Erlanger, M., and Gershon, D.: Studies on aging in nematodes. 2 Studies on the activities of several enzymes as a function of age. Exper. Gerontol. 5: 13–19, 1976.CrossRefGoogle Scholar
  33. 33.
    Gershon, H., and Gershon, D.: Detection of inactive enzyme molecules in ageing organisms. Nature, London, 227: 1214–1217, 1970.PubMedCrossRefGoogle Scholar
  34. 34.
    Zeelon, P., Gershon, H., and Gershon, D.: Inactive enzyme molecules in aging organisms. Nematode fructose-1, 6 diphosphate aldolase. Biochemistry, 12: 1743–1750, 1973.PubMedCrossRefGoogle Scholar
  35. 35.
    Reiss, U., and Rothstein, M.: Age-related changes in isocitrate lyase from the free-living nematode Turbatrix aceti. J. Biol. Chem., 250: 826–830, 1975.PubMedGoogle Scholar
  36. 36.
    Sharma, H., Gupta, S., and Rothstein, M.: Age-related alteration of enolase in the free-living nematode, Turbatrix actei. Arch. Biochem. Biophy. 174: 324–332, 1976.CrossRefGoogle Scholar
  37. 37.
    Gershon, H., Zeelon, P., and Gershon, D.: Faulty proteins: altered gene products in senescent cells and organisms. Advan. Exper. Med. Biol., 44: 255–264, 1974.Google Scholar
  38. 38.
    Gupta, S., and Rothstein, M.: A heat-stable factor which aggregates 3-phosphoglycerate kinase from Turbatrix aceti. Biochem. Biophys. Res. Comm., 69: 48–54, 1976.PubMedCrossRefGoogle Scholar
  39. 39.
    Gupta, S., K., and Rothstein, M.: Triosephosphate isomerase from young and old Turbatrix aceti. Arch. Biochem. Biophys. 174: 333–338, 1976.PubMedCrossRefGoogle Scholar
  40. 40.
    Samoiloff, M., and Pasternak, J.: Nematode morphogenesis; fine structure of the cuticle of each stage of the nematode, Panagrellus silusiae (de Man 1913) Goodey 1945. Can. J. Zool., 46: 1019–1022, 1968.PubMedCrossRefGoogle Scholar
  41. 41.
    Tilby, J. J., and Moses, V.: Nematode ageing: automatic maintenance of age-synchrony without inhibitors. Exper. Gerontol., 10: 213–223, 1975.CrossRefGoogle Scholar
  42. 42.
    Fatt, H. V.: Nutritional requirements for reproduction of a temperature sensitive nematode, reared in axenic culture. Proc. Soc. Exper. Biol. Med., 124: 897–903, 1967.Google Scholar
  43. 43.
    Hieb, W. F., and Rothstein, M.: Aging in the free-living nematode Turbatrix aceti. Techniques for synchronization and aging of large-scale axenic cultures. Exper. Gerontol. 10: 145–153, 1975.CrossRefGoogle Scholar
  44. 44.
    Lower, W. R., Hansen, E. L., and Yarwood, E. A.: Selection for adaptation to increased temperatures in free-living nematodes. Life Sciences, 7: 139–146, 1968.CrossRefGoogle Scholar
  45. 45.
    Zuckerman, B. M.: Nematodes as models for aging studies. In Croll, N.A. (Ed.). Organization of Nematodes, London, Academic Press, 211–241, 1976.Google Scholar
  46. 46.
    Lewis, M. Helmsing, P. J., and Ashburner, M.: Parallel changes in puffing activity and patterns of protein synthesis in salivary glands of Drosophila. Proc. Natl. Acad. Sci., USA, 72: 3604–3608, 1975.PubMedCrossRefGoogle Scholar
  47. 47.
    McKenzie, S. L., Henikoff, S., and Meselson, M.: Localization of RNA from heat-induced polysomes at puff sites in Drosophila melanogaster. Proc. Natl. Acad. Sci., USA, 72: 1117–1121, 1975.PubMedCrossRefGoogle Scholar
  48. 48.
    Spradling, A., Penman, S., and Pardue, M. L.: Analysis of Drosophila mRNA by in situ hybridization: sequences transcribed in normal and heat shocked culture cells. Cells, 4: 395–404, 1975.CrossRefGoogle Scholar
  49. 49.
    Kisiel, M., Nelson, B., and Zuckerman, B. M.: Effects of DNA synthesis inhibitors on Caenorhabditis briggsae and Turbatrix aceti. Nematologica, 18: 373–384, 1972.CrossRefGoogle Scholar
  50. 50.
    Kisiel, M., Himmelhoch, S., and Zuckerman, B. M.: Caenorhabditis briggsae: effects of aminopterin. Exper. Parsitol., 36: 430–438, 1974.CrossRefGoogle Scholar
  51. 51.
    Morris, J.: Histogensis and dependent glutamine synthetase inducibility in embryonic neural retina. Irreversible inhibition of differentiation by 5-bromodeoxyuridine. Develop. Biol., 35: 125–142, 1973.PubMedCrossRefGoogle Scholar
  52. 52.
    Rozenkranz, H. S., Pollak, R. D., and Schmidt, R. M.: Biologic effects of isohydroxyurea. Cancer Res., 29: 209–218, 1969.Google Scholar
  53. 53.
    Krowke, R., and Bochert, G.: Inhibitation of RNA synthesis, a possible mode of the embryotoxic action of hydroxyurea. Naunyn-Schmied Gerg’s Arch. Pharmacol., 288: 7–16, 1975.CrossRefGoogle Scholar
  54. 54.
    Knight, S. A.: Differentiation of Herpetomonas megaseliae; Effects of hydroxyurea on morphology and growth. J. Parasitol. 62: 515–522, 1976.PubMedCrossRefGoogle Scholar
  55. 55.
    Ramsier, H. P., Burkhalter, M., and Gautschi, J. R.: Survival of CHO cells that replicated DNA in the presence of hydroxyurea. Exper. Cell Res., 105: 445–453, 1977.CrossRefGoogle Scholar
  56. 56.
    Yarwood, E. A., and Hansen, E. L.: Dauer larvae of Caenorhabditis briggsaein axenic culture. J. Nematology, 1: 184–189, 1969.Google Scholar

Copyright information

© American Aging Association, Inc. 1978

Authors and Affiliations

  • Heinrich F. Klefenz
    • 1
  • Bert M. Zuckerman
    • 2
  1. 1.Institut für Biochemie I die Universität HeidelbergHeidelbergGermany
  2. 2.Laboratory of Experimental BiologyUniversity of MassachusettsEast Wareham

Personalised recommendations