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

作者：Aydemir Tolunay Beker; Troche Catalina; Kim Jinhee; Kim Min Hyun; Teran Oriana Y; Leeuwenburgh Christiaan; Cousins Robert J^*

来源：Experimental Gerontology, 2016, 85: 88-94.

DOI：10.1016/j.exger.2016.09.013

• Inflammation
• Sarcopenia
• Signaling pathways
• Interleukin-6
• Bone
• Growth

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-kappa 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.

• 出版日期2016-12