Calcium and Cellular Ageing

  • Alexej Verkhratsky
  • Emil Toescu


Calcium, an ubiquitous cytoplasmic second messenger, controls numerous physiological events and is also involved in cellular pathology. Either excess or deficit of cytoplasmic calcium could initiate cellular malfunction and result in cellular death. As will be highlighted in this volume, intracellular calcium is regulated by co-ordinated activity of several molecular cascades, represented by calcium transporters (i.e. ion channels, pumps and exchangers) and calcium binding proteins. Any unbalance of this delicate ensemble of calcium handling proteins may result in fatal consequences for living tissues.


Calcium Homeostasis Cellular Ageing Calcium Current Cerebellar Granule Neurone Cytoplasmic Calcium 
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. Barnes, C.A., 1988, Aging and the physiology of spatial memory, Neurobiol. Aging 9, 563–568.PubMedCrossRefGoogle Scholar
  2. Campbell, L.W., Hao, S.-Y., Thibault, O., Blalock, E.M. and Landfield, P.W., 1996, Aging changes in voltage-gated calcium currents in hippocampal CA1 neurones, J. Neurosci. 16, 6286–6295.PubMedGoogle Scholar
  3. Choi, D.W., 1994, Calcium and excitotoxic neuronal injury, Ann NY Acad Sci. 747, 162–171.PubMedCrossRefGoogle Scholar
  4. Colvin, R.A., Walker, J.P., Schummers, J. and Davis, N., 1996, Aging does not affect steady-state expression of the Na+/Ca2+ exchanger in rat brain, Cell Mol. Neurobiol. 16, 11–19.PubMedCrossRefGoogle Scholar
  5. De Jong, G.I., Naber, P.A., Van den Zee, E.A., Thompson, L.T., Disterhoft, J.F. and Luiten, P.G.M., 1996. Age-related loss of calcium binding proteins in rabbit hippocampus, Neurobiol. Aging 17, 459–465.PubMedCrossRefGoogle Scholar
  6. Duckies, S.P., Tsai, H. and Buchholz, J.N., 1996, Evidence for decline in intracellular calcium buffering in adrenergic nerves of aged rats, Life Sci. 58, 2029–2035.CrossRefGoogle Scholar
  7. Etcheberrigaray, E., Gibson, G.E. and Alkon, D.L., 1994, Molecular mechanisms of memory and the pathophysiology of Alzheimer’s disease, Ann. NY Acad. Sci. 747, 245–255.PubMedCrossRefGoogle Scholar
  8. Foster, T.C. and Norris, C.M., 1997, Age-associated changes in Ca2+-dependent processes: Relation to hippocampal synaptic plasticity, Hippocampus 7, 602–612.PubMedCrossRefGoogle Scholar
  9. Friel, D.D. and Tsien, R.W., 1992, A caffeine-and ryanodine-sensitive Ca2+ store in bullfrog sympathetic neurones modulates effects of Ca2+ entry on [Ca2+]i, J. Physiol. Lond. 450, 217–246.PubMedGoogle Scholar
  10. Gibson, G.E. and Peterson, C., 1987, Calcium and the aging nervous system, Neurobiol. Aging 8, 329–343.PubMedCrossRefGoogle Scholar
  11. Gibson, G.E., Perrino, P. and Dienel, G.A., 1986, In vivo brain calcium homeostasis during aging, Mech. Ageing. Dev. 37, 1–12.PubMedCrossRefGoogle Scholar
  12. Giovannelli, L. and Pepeu, G., 1989, Effect of age on K+-induced cytosolic Ca2+ changes in rat cortical synaptosomes, J. Neurochem. 53, 392–398.PubMedCrossRefGoogle Scholar
  13. Gomez-Isla, T., Price, J.L., McKell, D.W., Jr., Morris, J.C., Growdon, J.H. and Hyman, B.T., 1996, Profound loss of layer II entorhinal cortex neurones occurs in very mild Alzheimer’s disease, J. Neurosci. 16, 4491–4500.PubMedGoogle Scholar
  14. Ichas, F. and Mazat, J.-P., 1998, From calcium signaling to cell death: Two conformations for the mitochondrial permeability transition pore. Switching from low-to high-conductance state, Biochim. Biophys. Acta 1366, 33–50.PubMedCrossRefGoogle Scholar
  15. Igwe, O.J. and Filla, M.B., 1995, Regulaton of phosphainositide transduction system in the rat spinal cord during aging, Neuroscience 69, 1239–1251.PubMedCrossRefGoogle Scholar
  16. Igwe, O.J. and Filla, M.B., 1997, Aging-related regulation of two myo-inositol 1,4,5-trisphosphate signal transduction pathway in the rat striatum, Brain Res. Mol. Brain. Res 46, 39–53.PubMedCrossRefGoogle Scholar
  17. Igwe, O.J. and Ning, L., 1993, Inositol 1,4,5-trisphosphate arm of the phosphatidylinositide signal transduction pathway in the rat cerebellum during aging, Neurosci. Lett. 164, 167–170.PubMedCrossRefGoogle Scholar
  18. Ito, E., Oka, K., Etcheberrigaray, R., Nelson, T.J., McPhie, D.L., Tofel-Grehl, B., Gibson, G.E. and Alkon, D.L., 1994, Internal Ca2+ mobilization is altered in fibroblasts from patients with Alzheimer diseasem Proc. Natl. Acad. Sci, USA 91, 534–538.PubMedCrossRefGoogle Scholar
  19. Keller, B.U., 2000, The role of intracellular calcium signaling in motoneuron function and disease, this book.Google Scholar
  20. Khachaturian, Z.S., 1991, Calcium and the aging brain: Upsetting a delicate balance?, Geriatrics 46, 78–79.PubMedGoogle Scholar
  21. Khachaturian, Z.S., Cotman, C.W. and Pettegrew, W., 1989, Calcium, membranes, aging, and Alzheimer’s disease, Ann. NY Acad. Sci. 568, 1–292.PubMedCrossRefGoogle Scholar
  22. Kirischuk, S. and Verkhratsky, A., 1996, Calcium homeostasis in aged neurones, Life Sci. 59, 451–459.PubMedCrossRefGoogle Scholar
  23. Kirischuk, S., Pronchuk, N. and Verkhratsky, A., 1992, Measurements of intracellular calcium in sensory neurons of adult and old rats, Neuroscience 50, 947–951.PubMedCrossRefGoogle Scholar
  24. Kirischuk, S., Voitenko, N., Kostyuk, P. and Verkhratsky, A., 1996, Age associated changes of cytoplasmic calcium homeostasis in cerebellar granule neurons in situ: Investigation on thin cerebellar slices, Exp. Gerontology 31, 475–487.CrossRefGoogle Scholar
  25. Kostyuk, P., Pronchuk, N., Savchenko, A. and Verkhratsky, A., 1993, Calcium currents in aged rat dorsal root ganglion neurones, J. Physiol. Lond. 461, 467–483.PubMedGoogle Scholar
  26. Krzywkowski, P., De Bilbao, F., Senut, M.C. and Lamour, Y, 1995, Age-related changes in parvalbumin-and GABA-immunoreactive cells in the rat septum, Neurobiol. Aging 16, 29–40.PubMedCrossRefGoogle Scholar
  27. Krzywkowski, P., Potier, B., Billard, J.M., Dutar, P. and Lamour, Y., 1996, Synaptic mechanisms and calcium binding proteins in the aged rat brain, Life Sci. 59, 421–428.PubMedCrossRefGoogle Scholar
  28. Kurumatani, T., Fastbom, J., Bonkale, W.L., Bogdanovic, N., Winblad, B., Ohm, T.G. and Cowburn, R.F., 1998, Loss of inositol 1,4,5-trisphosphate receptor sites and decreased PKC levels correlate with staging of Alzheimer’s disease neurofibrillary pathology, Brain Res. 796, 209–221.PubMedCrossRefGoogle Scholar
  29. Landfield, P.W., 1988, Hippocampal neurobiological mechanisms of age-related memory dysfunction, Neurobiol. Aging 9, 571–579.PubMedCrossRefGoogle Scholar
  30. Leslie, S.W., Chandler, L.J., Barr, E. and Farrar, R.P., 1985, Reduced calcium uptake by rat brain mitochondrial and synaptosomes in responses to aging, Brain Res. 329, 177–183.PubMedCrossRefGoogle Scholar
  31. Lips, M.B. and Keller B.U., 1998, Endogenous calcium buffering in motoneurons of the nucleus hypoglossus from mouse, J. Physiol. Lond. 511, 105–117.PubMedCrossRefGoogle Scholar
  32. Martinez, A., Vitorica, J. and Satrustegui, J., 1988, Cytosolic free calcium levels increase with age in rat brain synaptosomes, Neurosci. Lett. 88, 336–342.PubMedCrossRefGoogle Scholar
  33. Martini, A., Battaini, F., Govoni, S. and Volpe, P., 1994, Inositol 1,4,5-trisphosphate receptor and ryanodine receptor in the aging brain of Wistar rats, Neurobiol. Aging 15, 203–206.PubMedCrossRefGoogle Scholar
  34. Mattson, M.P., Barger, S.W., Cheng, B., Lieberburg, I., Smith Swintosky, V.L. and Rydel, R.E., 1993, β-Amyloid precursor protein metabolites and loss of neuronal Ca2+ homeostasis in Alzheimer’s disease, Trends Neurosci. 16, 409–414.PubMedCrossRefGoogle Scholar
  35. Michaelis, M.L., Bigelow, D.J., Schoneich, C., Williams, T.D., Ramonda, L., Yin, D., Huhmer, A.F., Yao, Y., Gao, J. and Squier, T.C., 1996, Decreased plasma membrane calcium transport activity in aging brain, Life Sci. 59, 405–412.PubMedCrossRefGoogle Scholar
  36. Murchison, D. and Griffith, W.H., 1995, Low-voltage activated calcium currents increase in basal forebrain neurones from aged rats, J. Neurophysiol. 74, 876–887.PubMedGoogle Scholar
  37. Murchison, D. and Griffith, W.H., 1996, High-voltage-activated calcium currents in basal forebrain neurons during aging, J. Neurophysiol. 76, 158–174.PubMedGoogle Scholar
  38. Murchison, D. and Griffith, W.H., 1998, Increased calcium buffering in basal forebrain neurons during aging, J. Neurophysiol. 76, 350–364.Google Scholar
  39. Murchison, D. and Griffith, W.H., 1999, Age-related alterations in caffeine-sensitive calcium stores and mitochondrial buffering in rat basal forebrain, Cell Calcium 25, 439–452.PubMedCrossRefGoogle Scholar
  40. Neher, E., 1998, Usefulness and limitations of linear approximations to the understanding of Ca2+ signals, Cell Calcium 24, 345–357.PubMedCrossRefGoogle Scholar
  41. Novi, I., 1912, Le calcium et le magnésium du cerveau dans les différents âges, Arch. Ital. Biol. 58, 333–336.Google Scholar
  42. Pagliusi, S.R., Gerrard, P., Abdallah, M., Talabot, D. and Catsicas, S., 1994, Age-related changes in expression of AMPA-selective glutamate receptor subunits: Is calcium-permeability altered in hippocampal neurons?, Neuroscience 61, 429–433.PubMedCrossRefGoogle Scholar
  43. Papazafiri, P., Podini, P., Meldolesi, J. and Yamaguchi, T., 1995, Ageing affects cytosolic Ca2+ binding proteins and synaptic markers in the retina but not in cerebral cortex neurons of the rat, Neurosci. Lett. 186, 65–68.PubMedCrossRefGoogle Scholar
  44. Peterson, C. and Gibson, G.E., 1983, 3,4-diaminopyridine alter synaptosomal calcium uptake, J. Biol. Chem. 258, 11482–11486.PubMedGoogle Scholar
  45. Peterson, C., Gibson, G.E. and Blass, J.P., 1985, Altered calcium uptake in cultured skin fibroblasts from patients with Alzheimer’s disease, New Engl. J. Med. 312, 1063–1064.PubMedCrossRefGoogle Scholar
  46. Pozzan, T., Rizzuto, R., Volpe, P. and Meldolesi, J., 1994, Molecular and cellular physiology of intracellular calcium stores, Physiol. Rev. 74, 595–636.PubMedCrossRefGoogle Scholar
  47. Satrustegui, J., Villalba, M., Pereira, R., Bogonez, E. and Martinez Serrano, A., 1996, Cytosolic and mitochondrial calcium in synaptosomes during aging, Life Sci. 59, 429–434.PubMedCrossRefGoogle Scholar
  48. Thibault, O. and Landfield, P.W., 1996, Increase in single L-type calcium channels in hippocampal neurons during aging, Science 272, 1017–1020.PubMedCrossRefGoogle Scholar
  49. Thibault, O., Mazzanti, M.L., Blalock, E.M., Porter, N.M. and Landfield, P.W., 1995, Single-channel and whole-cell studies of calcium currents in young and aged rat hippocampal slice neurons, J. Neurosci. Methods 59, 77–83.PubMedCrossRefGoogle Scholar
  50. Thibault, O., Porter, N.M., Chen, K.C., Blalock, E.M., Kaminker, P.G., Clodfelter, G.V., Brewer, L.D. and Landfield, P.W., 1998, Calcium dysregulation in neuronal aging and Alzheimer’s disease: history and new directions, Cell Calcium 24, 417–433.PubMedCrossRefGoogle Scholar
  51. Toescu, E.C., 1998a, Apoptosis and cell death in neuronal cells: Where does calcium fit in?, Cell Calcium 24, 387–403.PubMedCrossRefGoogle Scholar
  52. Toescu, E.C., 1998b, Intraneuronal Ca2+ stores act mainly as a ‘Ca2+ sink’ in cerebellar granule neurones, Neuroreport 9, 1227–1231.PubMedCrossRefGoogle Scholar
  53. Verkhratsky, A. and Petersen, O.H., 1998, Neuronal calcium stores, Cell Calcium 24, 333–343.PubMedCrossRefGoogle Scholar
  54. Verkhratsky, A. and Shmigol, A., 1996, Calcium-induced calcium release in neurones, Cell Calcium 19, 1–14.PubMedCrossRefGoogle Scholar
  55. Verkhratsky, A., Shmigol, A., Kirischuk, S., Pronchuk, N. and Kostyuk, P., 1994, Age-dependent changes in calcium currents and calcium homeostasis in mammalian neurons, Ann. NY Acad. Sci. 747, 365–381.PubMedCrossRefGoogle Scholar
  56. Verkhratsky, A. and Toescu, E.C., 1998a, Calcium and neuronal ageing, Trends Neurosci. 21, 2–7.PubMedCrossRefGoogle Scholar
  57. Verkhratsky, A.N. and Toescu, E.C., 1998b, Integrative Aspects of Calcium Signalling, Plenum Press, London.Google Scholar
  58. Villa, A., Podini, P., Panzeri, M.C., Racchetti, G. and Meldolesi, J., 1994, Cytosolic Ca2+ binding proteins during rat brain ageing: Loss of calbindin and calretinin in the hippocampus, with no change in the cerebellum, Eur. J. Neurosci. 6, 1491–1499.PubMedCrossRefGoogle Scholar
  59. West, M.J., Coleman, P.D., Flood, D.G. and Troncoso, J.C., 1994, Differences in the pattern of hippocampal neuronal loss in normal ageing and Alzheimer’s disease, Lancet 344, 769–772.PubMedCrossRefGoogle Scholar
  60. Zipfel, G.J. and Choi, D.W, 1999, The changing landscape of ischaemic brain injury mechanisms, Nature 399(Suppl. 6738), A7–A14.PubMedGoogle Scholar
  61. Zipfel, G.J., Lee, J.M. and Choi, D.W, 1999, Reducing calcium overload in the ischemic brain, New Engl. J. Med. 341, 1543–1544.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2000

Authors and Affiliations

  • Alexej Verkhratsky
    • 1
  • Emil Toescu
    • 2
  1. 1.School of Biological SciencesManchester UniversityManchesterUK
  2. 2.Department of PhysiologyBirmingham UniversityBirminghamUK

Personalised recommendations