European Journal of Nutrition

, Volume 56, Issue 8, pp 2457–2466 | Cite as

Main biomarkers associated with age-related plasma zinc decrease and copper/zinc ratio in healthy elderly from ZincAge study

  • R. Giacconi
  • L. Costarelli
  • F. Piacenza
  • A. Basso
  • L. Rink
  • E. Mariani
  • T. Fulop
  • G. Dedoussis
  • G. Herbein
  • M. Provinciali
  • J. Jajte
  • I. Lengyel
  • E. Mocchegiani
  • M. Malavolta
Original Contribution



Zinc (Zn) plays an essential role in many biological processes including immune response. Impaired Zn status promotes immune dysfunction, and it has been associated with enhanced chronic inflammation during aging. It has been suggested that the measurement of circulating Zn by itself could not reflect the real Zn status of an individual. It is therefore necessary to identify other determinants associated with plasma Zn to better understanding how physiopathological conditions during aging may affect the concentration of this metal.


We have investigated the association between Zn levels and some biomarkers in 1090 healthy elderly from five European countries to increase the accuracy in the assessment of the Zn status. Stepwise multivariate linear regression models were used to analyze the influence of factors such as age, dietary intake, inflammatory mediators, laboratory parameters and polymorphisms previously associated with Zn homeostasis.


Plasma Zn decrement was most strongly predicted by age, while positive correlations were found with albumin, RANTES and Zn intake after adjustment for multiple confounders. HSP70 +1267 AA genotype was an independent factor associated with Zn plasma concentrations. Cu/Zn ratio was positively associated with markers of systemic inflammation and age and negatively associated with albumin serum levels.


Our findings show the most important independent determinants of plasma Zn concentration and Cu/Zn ratio variability in elderly population and suggest that the decline with age of Zn circulating levels is more dependent on physiopathological changes occurring with aging rather than to its nutritional intake.


Zinc plasma levels Inflammation Polymorphisms Zinc homeostasis Aging 



This study was supported by INRCA, European Commission (Project ZincAge: FOOD-CT-2003-506850; E. Mocchegiani, Coordinator) and COST Action TD1304 The Network for the Biology of Zinc (Zinc-Net).

Compliance with ethical standards

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Supplementary material

394_2016_1281_MOESM1_ESM.doc (123 kb)
Supplementary material 1 (DOC 123 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • R. Giacconi
    • 1
  • L. Costarelli
    • 1
  • F. Piacenza
    • 1
  • A. Basso
    • 1
  • L. Rink
    • 2
  • E. Mariani
    • 3
  • T. Fulop
    • 4
  • G. Dedoussis
    • 5
  • G. Herbein
    • 6
  • M. Provinciali
    • 7
  • J. Jajte
    • 8
  • I. Lengyel
    • 9
  • E. Mocchegiani
    • 1
  • M. Malavolta
    • 1
  1. 1.Translational Research Ctr. of Nutrition and Ageing, Scientific and Technological PoleItalian National Institute of Health and Science on Aging (INRCA)AnconaItaly
  2. 2.Institute of Immunology, Medical FacultyRWTH Aachen UniversityAachenGermany
  3. 3.Laboratory of Immunereumatology and Tissue Regeneration/RAMSES, Department of Medical and Surgical Sciences, Rizzoli Orthopedic InstituteUniversity of BolognaBolognaItaly
  4. 4.Department of Medicine, Faculty of Medicine, Research Center on AgingUniversity of SherbrookeSherbrookeCanada
  5. 5.Department of Dietetics and Nutritional ScienceHarokopio University of AthensAthensGreece
  6. 6.Department Pathogens and Inflammation EA 4266Université Bourgogne Franche-Comté, CHRU BesançonBesançonFrance
  7. 7.Advanced Technology Center for Aging Research, Scientific and Technological PoleItalian National Institute of Health and Science on Aging (INRCA)AnconaItaly
  8. 8.Department of Toxicology, Faculty of PharmacyMedical UniversityLodzPoland
  9. 9.UCL Institute of OphthalmologyUniversity College LondonLondonUK

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