Zinc, metallothioneins, and longevity - Effect of zinc supplementation: Zincage study

Eugenio Mocchegiani, Robertina Giacconi, Catia Cipriano, Laura Costarelli, Elisa Muti, Silvia Tesei, Cinzia Giuli, Roberta Papa, Fiorella Marcellini, Erminia Mariani, Lothar Rink, George Herbein, Audrey Varin, Tamas Fulop, Daniela Monti, Jolanta Jajte, George Dedoussis, Efstathios S. Gonos, Ioannis P. Trougakos, Marco Malavolta

Research output: Contribution to journalArticlepeer-review


Aging is an inevitable biological process that is associated with gradual and spontaneous biochemical and physiological changes and increased susceptibility to diseases. Because nutritional factors are involved in improvingimmune functions, metabolic harmony, and antioxidant defense, some nutritional factors, such as zinc, may modify susceptibility to disease and promote healthy aging. In vitro (human lymphocytes exposed to endotoxins) and in vivo (old or young mice fed with low zinc dietary intake) studies revealed that zinc is important for immune efficiency (innate and adaptive), antioxidant activity (supeoxide dismutase), and cell differentiation via clusterin/apolipoprotein J. Intracellular zinc homeostasis is regulated by metallothioneins (MT) via ion release through the reduction of thiol groups in the MT molecule. This process is crucial in aging because high MT levels are not able to release zinc, resulting in low intracellular free ion availability for biological functions. Improvement in these functions occurs in the elderly after physiological zinc supplementation. In this study, the selection of elderly subjects for zinc supplementation is discussed in relation to the genetic background of MT and pro-inflammatory cytokines, such as interleukin-6, because the latter is involved both in MT-gene expression and in intracellular zinc homeostasis.

Original languageEnglish
Pages (from-to)129-146
Number of pages18
JournalAnnals of the New York Academy of Sciences
Issue number1
Publication statusPublished - Nov 2007


  • Aging
  • Antioxidant activity
  • Genetic screening
  • Immune response
  • Longevity
  • Metallothioneins
  • Zinc
  • Zinc supplementation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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