Are Age-Related Changes in Receptor Activity an Expression of Altered Membrane Fluidity?

  • Kern Von Hungen
  • Claude F. Baxter


Among the various theories of aging, the membrane hypothesis of aging is particularly appealing (Sun and Sun, 1979; Grinna, 1977). Cellular membranes function in mediating and regulating active transport of substances across the cell boundary as well as serving as an important permeability barrier. Enzyme activities and receptor functions are also modulated by the lipid composition of membranes. The nature of membranes may change during aging either as a result of oxidative damage (Tappel, 1973) or from a deterioration of homeostatic mechanisms that maintain proper lipid composition (Kates and Kuksis, 1980). In vitro and in vivo manipulation of membrane lipids may thus provide a model of aging.


Membrane Fluidity Fluorescence Polarization Synaptic Membrane Dopaminergic Receptor Active Lipid 
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. Bonetti, A.C., Battistella, A., Calderini, G., Teolato, S., Crews, F.T., Gaiti, A., Algeri, S., and Toffano, G. (1983) Biochemical alterations in the mechanisms of synaptic transmission in aging brain. In: Samuel, D., et al. (eds.) Aging of the brain. New York: Raven, pp. 171–181.Google Scholar
  2. Borochov, H., and Shinitzky, M. (1976) Vertical displacement of membrane proteins mediated by changes in microviscosity. Proc. Natl. Acad. Sci. USA 73:4526–4530.PubMedCrossRefGoogle Scholar
  3. Calderini, G., Bonetti, A.C., Batistella, A., Crews F.T., and Toffano, G. (1983) Biochemical changes of rat brain membranes with aging. Neurochem. Res. 8:483–492.PubMedCrossRefGoogle Scholar
  4. Cimino, M., Valtini, G., Algeri, S., Curatola, G., Pezzoli, G., and Stramentinoli, G. (1984) Age-related modification of dopaminergic and beta-adrenergic receptor system: restoration to normal activity by modifying membrane fluidity with S-adenosylmethionine. Life Sci. 34:2029–2039.PubMedCrossRefGoogle Scholar
  5. Cooper, R.A. (1978) Influence of increased membrane cholesterol on membrane fluidity and cell function in human red blood cells. J. Supramol. Struct. 8:413–430.PubMedCrossRefGoogle Scholar
  6. Greenberg, L.H., and Weiss, B. (1978) Beta-adrenergic receptors in aged rat brain: reduced number and capacity of pineal gland to develop supersensitivity. Science 201:61–63.PubMedCrossRefGoogle Scholar
  7. Grinna, L.S. (1977) Changes in cell membranes during aging. Gerontology 23:452–464.PubMedCrossRefGoogle Scholar
  8. Hawthorne, J.N., and Pickard, M.R. (1979) Phospholipids in synaptic function. J. Neurochem. 32:5–14.PubMedCrossRefGoogle Scholar
  9. Heron, D.S., Shinitzky, M., Hershkowitz, M., and Samuel, D. (1980) Lipid fluidity markedly modulates the binding of serotonin to mouse brain membranes. Proc. Natl. Acad. Sci. USA 77:7463–7467.PubMedCrossRefGoogle Scholar
  10. Hershkowitz, M., Heron, D., Samuel, D., and Shinitzky, M. (1982) The modulation of protein phosphorylation and receptor binding in synaptic membranes by changes in lipid fluidity: implications for ageing. In: Gispen, W.H., and Routtenberg, A. (eds.) Progress in brain research, vol. 56. Amsterdam: Elsevier.Google Scholar
  11. Hitzemann, R.J., and Johnson, D.A. (1983) Developmental changes in synaptic membrane lipid composition and fluidity. Neurochem. Res. 8:121–131.PubMedCrossRefGoogle Scholar
  12. Horrocks, L.A., Sun, G.Y., and D’Amato, R.A. (1975) Changes in brain lipids during aging. In: Ordy, J.M., and Brizzee, K.R., (eds.) Neurobiology of aging. New York: Plenum.Google Scholar
  13. Joseph, J.A.V, and Roth, G.S. (1983) Age-related alterations in dopaminergic mechanisms. In: Samuel, D., et al., (eds.) Aging of the brain. New York: Raven.Google Scholar
  14. Kates, M.J and Kuksis, A. (1980) Membrane fluidity. In: Biophysical techniques and cellular regulation. Clifton, NJ: Humana.Google Scholar
  15. Kessler, A.R., Kessler, B., and Yehuda, S. (1985) Changes in the cholesterol level, cholesterol-to-phospholipid mole ratio, and membrane lipid microviscosity in rat brain induced by age and a plant oil mixture. Biochem. Pharmacol. 34:1120–1121.PubMedCrossRefGoogle Scholar
  16. Limbird, L.E., and Lefkowitz, R.J. (1976) Adenylate cyclase-coupled beta adrenergic receptors: effect of membrane lipid-perturbing agents on receptor binding the enzyme stimulation by catecholamines. Mol. Pharmacol. 12:559–567.PubMedGoogle Scholar
  17. Loh, H.H., and Law, P.Y. (1980) The role of membrane lipids in receptor mechanisms. Annu. Rev. Pharmacol. Toxicol. 20:201–234.PubMedCrossRefGoogle Scholar
  18. Lyte, M., and Shinitzky, M. (1985) A special lipid mixture for membrane fluidization. Biochim. Biophys. Acta 812:133–138.PubMedCrossRefGoogle Scholar
  19. Maggi, A., Schmidt, M.J., Ghetti, B., and Enna, S.J. (1979) Effect of aging on neurotransmitter receptor binding in rat and human brain. Life Sci. 24:367–374.PubMedCrossRefGoogle Scholar
  20. Marcusson, J., Oreland, L., and Winblad, B. (1984) Effect of age on human brain serotonin (S-l) binding sites.Google Scholar
  21. Misra, C.H., Shelat, H.S., and Smith, R.C. (1980) Effect of age on adrenergic and dopaminergic receptor binding in rat brain. Life Sci. 27:521–526.PubMedCrossRefGoogle Scholar
  22. Morin, A.M., and Wasterlain, C.G. (1980) Aging and rat brain muscarinic receptors as measured by quinuclidinyl benzylate binding. Neurochem. Res. 5:301–308.PubMedCrossRefGoogle Scholar
  23. Moroi, K., and Hsu, L.L. (1983) Dopamine receptors: effects of phosphatidyl choline. Trans. Am. Soc. Neurochem. 14:158.Google Scholar
  24. Nagy, K., Simon, P., and Zs.-Nagy, I. (1983) Spin label studies on synaptosomal membranes of rat brain cortex during aging. Biochem. Biophys. Res. Commun. 117:688–694.PubMedCrossRefGoogle Scholar
  25. Norton, W.T., and Poduslo, S.E. (1973) Myelination in rat brain: changes in myelin composition during brain maturation. J. Neurochem. 21:759–773.PubMedCrossRefGoogle Scholar
  26. O’Connor, S.W., Scarpace, P.J., and Abrass, I.B. (1984) The effect of age and cholesterol on the rat lung beta-adrenergic system. Biochim. Biophys. Acta 778:497–502.PubMedCrossRefGoogle Scholar
  27. Sandermann, H. (1978) Regulation of membrane enzymes by lipids. Biochim. Biophys. Acta 515:209–237.PubMedGoogle Scholar
  28. Severson, J.A., and Finch, C.E. (1980) Reduced dopaminergic binding during aging in rodent striatum. Brain Res. 192:147–162.PubMedCrossRefGoogle Scholar
  29. Severson, J.A., Marcusson, J., Winblad, B., and Finch, C.E. (1983) Age-correlated loss of dopaminergic binding sites in human basal ganglia. J. Neurochem. 39:1623–1631.CrossRefGoogle Scholar
  30. Shih, J.C., and Ohsawa, R. (1983) Differential effect of cholesterol on two types of 5-hydroxytryptamine binding sites. Neurochem. Res. 8:701–710.PubMedCrossRefGoogle Scholar
  31. Shih, J.C., and Young, H. (1978) The alteration of serotonin binding sites in aged human brain. Life Sci. 23:1441–1448.PubMedCrossRefGoogle Scholar
  32. Shinitzky, M. (1984) Membrane fluidity and cellular functions. In: Shinitzky, M. (ed.) Physiology of membrane fluidity, vol. 1. Boco Raton, FL: CRC Press, pp. 1–51.Google Scholar
  33. Shinitzky, M., and Berenholz, Y. (1978) Fluidity parameters of lipid regions determined by fluorescence polarization. Biochim. Biophys. Acta 515:367–394.PubMedGoogle Scholar
  34. Shinitzky, M., Heron, D.S., and Samuel, D. (1983) Restoration of membrane fluidity and serotonin receptors in the aged mouse brain. In: Samuel, D., et al., (eds.) Aging of the brain, New York: Raven.Google Scholar
  35. Stubbs, C.D., and Smith, A.D. (1984) The modification of mammalian membrane polyunsaturated fatty acid composition in relation to membrane fluidity and function. Biochim. Biophys. Acta 779:89–137.PubMedGoogle Scholar
  36. Sun, A.Y., and Sun G.Y. (1979) Neurochemical aspects of the membrane hypothesis of aging. Interdiscipl. Top. Gerontol. 15:34–53.Google Scholar
  37. Tappel, A.L., Fletcher, B., and Deamer, D. (1973) Effect of antioxidants and nutrients on lipid peroxidation fluorescent products and aging parameters in the mouse. J. Gerontol 28:415–424.PubMedGoogle Scholar
  38. Thang, N.X., Borsodi, A., and Wolleman, M. (1980) Effects of phospholipids on the binding of 3H-dihydroalprenolol to the beta adrenergic receptor of rabbit heat membranes. Biochem. Pharmacol. 29:2791–2797.PubMedCrossRefGoogle Scholar
  39. Von Hungen, K., Derby, P., and Baxter, C.F. (1987) Modulation of serotonin receptors by specific phosphatidylcholines. Neurochem. Internat. (in press).Google Scholar
  40. Wince, L.C., and Rutledge, C.O. (1981) The effect of dietary lipid on the 3H-dihydroalprenolol and adenylate cyclase activity in rat atria. J. Pharmacol. Exp. Ther. 219:625–631.PubMedGoogle Scholar
  41. Wood, W.G., Strong, R., Williamson, L.S., and Wise, R.W. (1984) Changes in lipid composition of cortical synaptosomes from different age groups of mice. Life Sci. 35:1947–1952.PubMedCrossRefGoogle Scholar
  42. Yeagle, P.L. (1985) Cholesterol and the cell membrane. Biochim. Biophys. Acta 822:267–287.PubMedGoogle Scholar

Copyright information

© Martinus Nijhoff Publishing, Boston 1987

Authors and Affiliations

  • Kern Von Hungen
  • Claude F. Baxter

There are no affiliations available

Personalised recommendations