title: Aging amplifies multiple phenotypic defects in mice with zinc transporter Zip14 (Slc39a14) deletion.
abstract: Inflammation and zinc dyshomeostasis are two common hallmarks of aging. A major zinc transporter ZIP14 (slc39a14) is upregulated by proinflammatory stimuli, e.g. interleukin-6. We have evaluated the influence of age on the Zip14 KO phenotype using wild-type (WT) and Zip14 knockout (KO) mice. Aging produced a major increase in serum IL-6 concentrations that was dramatically augmented in the Zip14 KO mice. In keeping with enhanced serum IL-6 concentrations, aging produced tissue-specific increases in zinc concentration of skeletal muscle and white adipose tissue. Metabolic endotoxemia produced by Zip14 ablation is maintained in aged KO mice. Muscle non-heme iron (NHI) was increased in aged WT mice but not in aged Zip14 KO mice demonstrating NHI uptake by muscle is ZIP14-dependent and increases with age. NF-κB and STAT3 activation was greater in aged mice, but was tissue specific and inversely related to tissue zinc. Micro-CT analysis revealed that Zip14 KO mice had markedly reduced trabecular bone that was greatly amplified with aging. These results demonstrate that the inflammation-responsive zinc transporter ZIP14 has phenotypic effects that are amplified with aging.
authors.affiliation: Food Science and Human Nutrition Department, Center for Nutritional Sciences, College of Agriculture and Life Sciences, University of Florida, Gainesville, FL, United States.
authors.forename: Tolunay Beker
authors.initials: TB
authors.lastname: Aydemir
authors.affiliation: Food Science and Human Nutrition Department, Center for Nutritional Sciences, College of Agriculture and Life Sciences, University of Florida, Gainesville, FL, United States.
authors.forename: Catalina
authors.initials: C
authors.lastname: Troche
authors.affiliation: Food Science and Human Nutrition Department, Center for Nutritional Sciences, College of Agriculture and Life Sciences, University of Florida, Gainesville, FL, United States.
authors.forename: Jinhee
authors.initials: J
authors.lastname: Kim
authors.affiliation: Food Science and Human Nutrition Department, Center for Nutritional Sciences, College of Agriculture and Life Sciences, University of Florida, Gainesville, FL, United States.
authors.forename: Min-Hyun
authors.initials: MH
authors.lastname: Kim
authors.affiliation: Food Science and Human Nutrition Department, Center for Nutritional Sciences, College of Agriculture and Life Sciences, University of Florida, Gainesville, FL, United States.
authors.forename: Oriana Y
authors.initials: OY
authors.lastname: Teran
authors.affiliation: Department of Aging and Geriatric Research, College of Medicine, University of Florida, Gainesville, FL, United States; Institute on Aging, College of Medicine, University of Florida, Gainesville, FL, United States.
authors.forename: Christiaan
authors.initials: C
authors.lastname: Leeuwenburgh
authors.affiliation: Food Science and Human Nutrition Department, Center for Nutritional Sciences, College of Agriculture and Life Sciences, University of Florida, Gainesville, FL, United States. Electronic address: cousins@ufl.edu.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Cousins
mesh_terms: D052436:Adipose Tissue, White / Q000378:metabolism; D000375:Aging / Q000378:metabolism*; D000818:Animals; D000071556:Cancellous Bone / Q000378:metabolism; D027682:Cation Transport Proteins / Q000235:genetics*; D017353:Gene Deletion; D007249:Inflammation / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation; D015032:Zinc / Q000378:metabolism*
chemical_list: D027682:Cation Transport Proteins; D015850:Interleukin-6; D016328:NF-kappa B; C500556:SLC39A14 protein, mouse; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; C577686:interleukin-6, mouse; D015032:Zinc
keywords: Bone; Growth; Inflammation; Interleukin-6; Sarcopenia; Signaling pathways