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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-?B 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.

SUBMITTER: Aydemir TB 

PROVIDER: S-EPMC5101137 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Aging amplifies multiple phenotypic defects in mice with zinc transporter Zip14 (Slc39a14) deletion.

Aydemir Tolunay Beker TB   Troche Catalina C   Kim Jinhee J   Kim Min-Hyun MH   Teran Oriana Y OY   Leeuwenburgh Christiaan C   Cousins Robert J RJ  

Experimental gerontology 20160916


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  ...[more]

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