Research Paper Volume 12, Issue 13 pp 13762—13790

Aging affects sex- and organ-specific trace element profiles in mice

Kristina Lossow1,2,3,4, , Johannes F. Kopp2,4, , Maria Schwarz1,4, , Hannah Finke2, , Nicola Winkelbeiner2,4, , Kostja Renko5,6, , Xheni Meçi5, , Christiane Ott3,7, , Wiebke Alker4,8, , Julian Hackler4,5, , Tilman Grune3, , Lutz Schomburg4,5, , Hajo Haase4,8, , Tanja Schwerdtle2,4,6, *, , Anna P. Kipp1,4, *, ,

  • 1 Department of Molecular Nutritional Physiology, Institute of Nutritional Sciences, Friedrich Schiller University Jena, Jena, Germany
  • 2 Department of Food Chemistry, Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany
  • 3 German Institute of Human Nutrition, Nuthetal, Germany
  • 4 TraceAge-DFG Research Unit on Interactions of Essential Trace Elements in Healthy and Diseased Elderly, Potsdam-Berlin-Jena, Germany
  • 5 Institute for Experimental Endocrinology, Charité University Medical School Berlin, Berlin, Germany
  • 6 German Federal Institute for Risk Assessment (BfR), Berlin, Germany
  • 7 DZHK German Centre for Cardiovascular Research, Berlin, Germany
  • 8 Department of Food Chemistry and Toxicology, Technische Universität Berlin, Berlin, Germany
* Equal contribution

Received: January 9, 2020       Accepted: June 13, 2020       Published: July 3, 2020
How to Cite

Copyright © 2020 Lossow et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


A decline of immune responses and dynamic modulation of the redox status are observed during aging and are influenced by trace elements such as copper, iodine, iron, manganese, selenium, and zinc. So far, analytical studies have focused mainly on single trace elements. Therefore, we aimed to characterize age-specific profiles of several trace elements simultaneously in serum and organs of adult and old mice. This allows for correlating multiple trace element levels and to identify potential patterns of age-dependent alterations. In serum, copper and iodine concentrations were increased and zinc concentration was decreased in old as compared to adult mice. In parallel, decreased copper and elevated iron concentrations were observed in liver. The age-related reduction of hepatic copper levels was associated with reduced expression of copper transporters, whereas the increased hepatic iron concentrations correlated positively with proinflammatory mediators and Nrf2-induced ferritin H levels. Interestingly, the age-dependent inverse regulation of copper and iron was unique for the liver and not observed in any other organ. The physiological importance of alterations in the iron/copper ratio for liver function and the aging process needs to be addressed in further studies.


ARE/EpRE: antioxidant/electrophilic response elements; ATP7A: ATPase copper transporting alpha; ATP7B: ATPase copper transporting beta; cDNA: complementary DNA; CTAB: cetyltrimethylammonium bromide; CDNB: 1-chloro-2,4-dinitrobenzene; Cp: ceruloplasmin; Ctr1: solute carrier family 31: member 1; Cu: copper; DEPC: diethyl dicarbonate; Dio1: deiodinase 1; DMT1: solute carrier family 11 (proton-coupled divalent metal ion transporters): member 2; DTNB: 5,5’-dithiobis(2-nitrobenzoic acid); DTT: 1,4-Dithiothreitol; ECL: enhanced chemiluminescence; EDTA: ethylenediaminetetraacetic acid; ELISA: enzyme-linked immunosorbent assay; Fe: iron; Fpn: ferroportin, solute carrier family 40 (iron-regulated transporter), member 1; FTH: ferritin H; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GPX: glutathione peroxidase; GSH: glutathione; GST: glutathione S-transferase; hmdC/dC: global DNA hydroxymethylation; HPLC: high-performance liquid chromatography; Hprt1: hypoxanthine-guanine phosphoribosyltransferase 1; I: iodine; ICP-MS/MS: inductively coupled plasma tandem mass spectrometry; IL1β: interleukin 1 beta; IL6: interleukin 6; KEAP1: Kelch-like ECH-associated protein 1; KPO4: monopotassium phosphate; LC: liquid chromatography; mdC/dC: global DNA methylation; Mn: manganese; MS/MS: tandem mass spectrometer; MT: metallothionein; MTT: 3-(4, 5-dimethylthiazol-2-yl)-2: 5-diphenyltetrazolium bromide; NADPH: nicotinamide adenine dinucleotide phosphate (NADP) bonded with a hydrogen; NIS: solute carrier family 5 (sodium iodide symporter): member 5; NQO1: NAD(P)H:quinone oxidoreductase; Nrf2: nuclear factor (erythroid-derived 2)-like 2; PBS: phosphate-buffered saline; PTU: 6-n-propyl-2-thio-uracil; qRT-PCR: quantitative reverse transcription polymerase chain reaction; Rh: rhodium; Rpl13a: ribosomal protein L13a; rS: Spearman´s correlation coefficient; RT: room temperature; rT3: reverse triiodothyronine; SDS: sodium dodecyl sulfate; Se: selenium; Selenop: selenoprotein P; Slc48a1: solute carrier family 48 (heme transporter), member 1; TE(s): trace element(s); TET: ten-eleven-translocation; Tfrc: transferrin receptor; TNF(α): tumor necrosis factor-alpha; Zip4: solute carrier family 39, member 4; Zip8: solute carrier family 39, member 8; Zip14: solute carrier family 39, member 14; Zn: zinc; ZnT1: solute carrier family 30, member 1 (Slc30a1); ZnT10: solute carrier family 30, member 10 (Slc30a10); 3-NT: 3-nitrotyrosine.