title: Main biomarkers associated with age-related plasma zinc decrease and copper/zinc ratio in healthy elderly from ZincAge study.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Translational Research Ctr. of Nutrition and Ageing, Scientific and Technological Pole, Italian National Institute of Health and Science on Aging (INRCA), Ancona, Italy. r.giacconi@inrca.it.
authors.forename: R
authors.identifier: http://orcid.org/0000-0002-1468-2140
authors.initials: R
authors.lastname: Giacconi
authors.affiliation: Translational Research Ctr. of Nutrition and Ageing, Scientific and Technological Pole, Italian National Institute of Health and Science on Aging (INRCA), Ancona, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Costarelli
authors.affiliation: Translational Research Ctr. of Nutrition and Ageing, Scientific and Technological Pole, Italian National Institute of Health and Science on Aging (INRCA), Ancona, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Piacenza
authors.affiliation: Translational Research Ctr. of Nutrition and Ageing, Scientific and Technological Pole, Italian National Institute of Health and Science on Aging (INRCA), Ancona, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Basso
authors.affiliation: Institute of Immunology, Medical Faculty, RWTH Aachen University, Aachen, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Rink
authors.affiliation: Laboratory of Immunereumatology and Tissue Regeneration/RAMSES, Department of Medical and Surgical Sciences, Rizzoli Orthopedic Institute, University of Bologna, Bologna, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Mariani
authors.affiliation: Department of Medicine, Faculty of Medicine, Research Center on Aging, University of Sherbrooke, Sherbrooke, Canada.
authors.forename: T
authors.initials: T
authors.lastname: Fulop
authors.affiliation: Department of Dietetics and Nutritional Science, Harokopio University of Athens, Athens, Greece.
authors.forename: G
authors.initials: G
authors.lastname: Dedoussis
authors.affiliation: Department Pathogens and Inflammation EA 4266, Université Bourgogne Franche-Comté, CHRU Besançon, Besançon, France.
authors.forename: G
authors.initials: G
authors.lastname: Herbein
authors.affiliation: Advanced Technology Center for Aging Research, Scientific and Technological Pole, Italian National Institute of Health and Science on Aging (INRCA), Ancona, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Provinciali
authors.affiliation: Department of Toxicology, Faculty of Pharmacy, Medical University, Lodz, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Jajte
authors.affiliation: UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London, UK.
authors.forename: I
authors.initials: I
authors.lastname: Lengyel
authors.affiliation: Translational Research Ctr. of Nutrition and Ageing, Scientific and Technological Pole, Italian National Institute of Health and Science on Aging (INRCA), Ancona, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Mocchegiani
authors.affiliation: Translational Research Ctr. of Nutrition and Ageing, Scientific and Technological Pole, Italian National Institute of Health and Science on Aging (INRCA), Ancona, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Malavolta
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D015415:Biomarkers / Q000097:blood*; D018946:Chemokine CCL5 / Q000235:genetics / Q000378:metabolism; D015331:Cohort Studies; D003300:Copper / Q000008:administration & dosage / Q000097:blood*; D004032:Diet; D038441:Diet, Mediterranean; D005060:Europe; D005260:Female; D060005:Genotyping Techniques; D006706:Homeostasis; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000503:physiopathology; D008297:Male; D009752:Nutritional Status; D012709:Serum Albumin / Q000378:metabolism; D015032:Zinc / Q000008:administration & dosage / Q000097:blood*
chemical_list: D015415:Biomarkers; C483024:CCL5 protein, human; D018946:Chemokine CCL5; D012709:Serum Albumin; D003300:Copper; D015032:Zinc
keywords: Aging; Inflammation; Polymorphisms; Zinc homeostasis; Zinc plasma levels