Zinc, immune plasticity, aging, and successful aging: Role of metallothionein

Eugenio Mocchegiani, Robertina Giacconi, Elisa Muti, Cinzia Rogo, Massimo Bracci, Mario Muzzioli, Catia Cipriano, Marco Malavolta

Research output: Contribution to journalArticlepeer-review


The capacity of the remodeling immune responses during stress (immune plasticity) is fundamental to reach successful aging. We herein report two pivotal models to demonstrate the relevance of the immune plasticity in aging and successful aging. One model is represented by the circadian rhythms of immine responses; the other one is the immune responses during partial hepatectomy/liver regeneration (pHx). The latter is suggestive because it mimics the immunosenescence and chronic inflammation 48 hours after partial hepatectomy in the young through the continuous production of IL-6, which is the main cause of immune plasticity lack in aging. The constant production of IL-6 leads to abnormal increments of zinc-bound metallothionein (MT), which is, in turn, unable in zinc release in aging. As a consequence, low zinc ion bioavailability appears for thymic and extrathymic immune efficiency, in particular, of liver NKT cells bearing TCR gd. The remodeling during the circadian cycle and during pHx of zinc-bound MT confers the immune plasticity of liver NKT γδ cells and NK cells in young and very old age, not in old age. Therefore, zinc-bound MT homeostasis is crucial in conferring liver immune plasticity with subsequent successful aging.

Original languageEnglish
Pages (from-to)127-134
Number of pages8
JournalAnnals of the New York Academy of Sciences
Publication statusPublished - 2004


  • Aging
  • Circadian cycle
  • gp130
  • IL-6
  • Immune plasticity
  • Liver extrathymic T cell pathway
  • Liver regeneration
  • Metallothionein
  • NKT αβ and γδ cells
  • NKT cells
  • PARP-1
  • Partial hepatectomy
  • Successful aging
  • Zinc

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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