Synaptic and mitochondrial physiopathologic changes in the aging nervous system and the role of zinc ion homeostasis

Carlo Bertoni-Freddari, Eugenio Mocchegiani, Marco Malavolta, Tiziana Casoli, Giuseppina Di Stefano, Patrizia Fattoretti

Research output: Contribution to journalArticlepeer-review


Brain performances, e.g. learning and memory, decay during aging. Deterioration of synaptic junctions, as structural correlates of these key functions of the central nervous system, may play a central role in this impairment. Current research on the age-related changes of synapses is documenting that the numeric loss of contacts appears to trigger a compensatory reaction by the old CNS, i.e. the surviving junctional areas in old individuals are larger than in adult subjects. The final outcome of the balanced changes in synaptic number and size is that the overall synaptic junctional area per cubic micron of neuropil is also reduced in aging and this may account for the age-associated functional decay of CNS performances. Among the suggested determinants of synaptic deterioration in aging, a considerable number of recent studies support an early and pivotal role of the progressive decline of the mitochondrial metabolic competence, i.e. the capacity of select pools of organelles to provide adequate amounts of adenosine triphosphate. Quantitative ultrastructural studies together with cytochemistry of key enzymes of the respiratory chain (cytochrome oxidase and succinic dehydrogenase) have shown that mitochondrial dysfunctions play an early and central role in synaptic deterioration events associated with aging and neurodegenerative diseases. Among the various causes, the multiple mechanisms and molecules involved in zinc ion homeostasis have been supposed to be less efficient in the aging brain. Thus, a transient imbalance of free zinc ion concentration in the cytosol ([Zn2+]i) can be considered an unfavourable trigger of subtle mitochondrial damage and synaptic pathology.

Original languageEnglish
Pages (from-to)590-596
Number of pages7
JournalMechanisms of Ageing and Development
Issue number6
Publication statusPublished - Jun 2006


  • Cytochrome oxidase
  • Mitochondrial metabolic competence
  • Mitochondrial pathology
  • Succinic dehydrogenase
  • Synaptic pathology
  • Zinc ion homeostasis
  • Zinc toxicity

ASJC Scopus subject areas

  • Ageing
  • Biochemistry
  • Developmental Biology
  • Developmental Neuroscience


Dive into the research topics of 'Synaptic and mitochondrial physiopathologic changes in the aging nervous system and the role of zinc ion homeostasis'. Together they form a unique fingerprint.

Cite this