Brain aging: The zinc connection

Carlo Bertoni-Freddari, Patrizia Fattoretti, Tiziana Casoli, Giuseppina Di Stefano, Belinda Giorgetti, Marta Balietti

Research output: Contribution to journalArticlepeer-review


At variance with other organs, where the functional and structural units are repeated, the brain is a composite assembly of groups of cells with different metabolic features and functional units. Deterioration of brain function occurs when the number of neurons or their connections decrease below a critical reserve level and coping with environmental stimulation is seriously hampered. Physiopathological alterations of the synaptic junctional areas are reported to play a central role in the process of brain aging. Current research is documenting an age-related numeric loss of synapses which is paired by a significant enlargement of the persisting contact zones: the final outcome of these balanced changes is a significant reduction of the overall synaptic junctional area per unit volume of neuropil. The progressive decline of the mitochondrial metabolic competence, i.e. the capacity of select pools of organelles to provide adequate amounts of adenosine triphosphate is supposed to represent a key determinant in synaptic aging. Cytochemical estimations of the activity of cytochrome oxidase confirm that mitochondrial dysfunctions play an early role in synaptic deterioration. Zinc ions act as physiological neuromodulators at glutamatergic synapses, however, in order to avoid neurotoxic damage, the intracellular free Zn++ concentration ([Zn++]i) must be tightly controlled by: (i) extrusion (Zn++ transporters); (ii) buffering (metallothioneins) and (iii) sequestration (mitochondria) systems. In physiological aging, if any of these systems is impaired and/or not adequately coordinated with the other two, the resulting significant rise of ([Zn++]i) may inhibit the cellular energy providing systems and affect mitochondria as primary target.

Original languageEnglish
Pages (from-to)389-393
Number of pages5
JournalExperimental Gerontology
Issue number5
Publication statusPublished - May 2008


  • Brain aging
  • Mitochondrial dysfunction
  • Mitochondrial metabolic competence
  • Synaptic pathology
  • Synaptic plasticity
  • Zinc homeostasis

ASJC Scopus subject areas

  • Ageing
  • Medicine(all)


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