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Zinc: dietary intake and impact of supplementation on immune function in elderly

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Abstract

The diet in the elderly does not provide a sufficient level of nutrients needed to maintain an adequate healthy status leading to micronutrient deficiencies and impaired immune response with subsequent development of degenerative diseases. Nutrient “zinc” is a relevant micronutrient involved in maintaining a good integrity of many body homeostatic mechanisms, including immune efficiency, owing to its requirement for the biological activity of many enzymes, proteins and for cellular proliferation and genomic stability. Old people aged 60–65 years and older have zinc intakes below 50% of the recommended daily allowance on a given day. Many causes can be involved: among them, altered intestinal absorption, inadequate mastication, psychosocial factors, drugs interactions, altered subcellular processes (zinc transporters (Zip and ZnT family), metallothioneins, divalent metal transporter-1). Zinc supplementation may remodel the immune alterations in elderly leading to healthy ageing. Several zinc trials have been carried out with contradictory data, perhaps due to incorrect choice of an effective zinc supplementation in old subjects showing subsequent zinc toxic effects on immunity. Old subjects with specific IL-6 polymorphism (GG allele carriers; named C−) are more prone for zinc supplementation than the entire old population, in whom correct dietary habits with foods containing zinc (Mediterranean diet) may be sufficient in restoring zinc deficiency and impaired immune response. We summarise the main causes of low zinc dietary intake in elderly reporting an update on the impact of zinc supplementation upon the immune response also on the basis of individual IL-6 polymorphism.

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References

  • Abo T, Kawamura T, Watanabe H (2000) Physiological responses of extrathymic T cells in the liver. Immunol Rev 174:135–149

    PubMed  CAS  Google Scholar 

  • Andree KB, Kim J, Kirschke CP, Gregg JP, Paik H, Joung H, Woodhouse L, King JC, Huang L (2004) Investigation of lymphocyte gene expression for use as biomarkers for zinc status in humans. J Nutr 134:1716–1723

    PubMed  CAS  Google Scholar 

  • Andriollo-Sanchez M, Hininger-Favier I, Meunier N, Toti E, Zaccaria M, Brandolini-Bunlon M, Polito A, O’Connor JM, Ferry M, Coudray C, Roussel AM (2005) Zinc intake and status in middle-aged and older European subjects: the ZENITH study. Eur J Clin Nutr 59:S37–S41

    PubMed  CAS  Google Scholar 

  • Araujo LM, Lefort J, Nahori MA, Diem S, Zhu R, Dy M, Leite-de-Moraes MC, Bach JF, Vargaftig BB, Herbelin A (2004) Exacerbated Th2-mediated airway inflammation and hyperresponsiveness in autoimmune diabetes-prone NOD mice: a critical role for CD1d-dependent NKT cells. Eur J Immunol 34:327–335

    PubMed  CAS  Google Scholar 

  • Arnold CR, Wolf J, Brunner S, Herndler-Brandstetter D, Grubeck-Loebenstein B (2011) Gain and loss of T cell subsets in old age—age-related reshaping of the T cell repertoire. J Clin Immunol 31:137–146

    PubMed  Google Scholar 

  • August D, Janghorbani M, Young VR (1989) Determination of zinc and copper absorption at three dietary Zn–Cu ratios by using stable isotope methods in young adult and elderly subjects. Am J Clin Nutr 50:1457–1463

    PubMed  CAS  Google Scholar 

  • Balesaria S, Hogstrand C (2006) Identification, cloning and characterization of a plasma membrane zinc efflux transporter TrZnT-1, from fugu pufferfish (Takifugu rubripes). Biochem J 394:485–493

    PubMed Central  PubMed  CAS  Google Scholar 

  • Bao S, Liu MJ, Lee B, Besecker B, Lai JP, Guttridge DC, Knoell DL (2010) Zinc modulates the innate immune response in vivo to polymicrobial sepsis through regulation of NF-kappaB. Am J Physiol Lung Cell Mol Physiol 298:L744–L754

    PubMed Central  PubMed  CAS  Google Scholar 

  • Basu TK, Donaldson D (2003) Intestinal absorption in health and disease: micronutrients. Best Pract Res Clin Gastroenterol 17:957–979

    PubMed  CAS  Google Scholar 

  • Biron CA, Brossay L (2001) NK cells and NKT cells in innate defense against viral infections. Curr Opin Immunol 13:458–464

    PubMed  CAS  Google Scholar 

  • Bjelakovic G, Gluud C (2011) Vitamin and mineral supplement use in relation to all-cause mortality in the Iowa Women’s Health Study. Arch Intern Med 171:1633–1634

    PubMed  Google Scholar 

  • Bogden JD (2004) Influence of zinc on immunity in the elderly. J Nutr Health Aging 8:48–54

    PubMed  CAS  Google Scholar 

  • Bonafe M, Olivieri F, Cavallone L, Giovagnetti S, Marchegiani F, Cardelli M, Pieri C, Marra M, Antonicelli R, Lisa R, Rizzo MR, Paolisso G, Monti D, Franceschi C (2001) A gender-dependent genetic predisposition to produce high levels of IL-6 is detrimental for longevity. Eur J Immunol 31:2357–2361

    PubMed  CAS  Google Scholar 

  • Briefel RR, Bialostosky K, Kennedy-Stephenson JJ, McDowell MA, Ervin RB, Wright JD (2000) Zinc intake of the U.S. population. Findings from the third National Health and Nutrition Examination Survey 1988–1994. J Nutr 130:1367S–1373S

    PubMed  CAS  Google Scholar 

  • Bruunsgaard H, Pedersen AN, Schroll M, Skinhoj P, Pedersen BK (1999) Impaired production of proinflammatory cytokines in response to lipopolysaccharide (LPS) stimulation in elderly humans. Clin Exp Immunol 118:235–241

    PubMed Central  PubMed  CAS  Google Scholar 

  • Bunk MJ, Dnistrian AM, Schwartz MK, Rivlin RS (1989) Dietary Zn deficiency decreases plasma concentrations of vitamin E. Proc Soc Exp Biol Med 190:379–384

    PubMed  CAS  Google Scholar 

  • Cakman I, Rohwer J, Schutz RM, Kirchner H, Rink L (1996) Dysregulation between TH1 and TH2 T cell subpopulations in the elderly. Mech Ageing Dev 87:197–209

    PubMed  CAS  Google Scholar 

  • Cakman I, Kirchner H, Rink L (1997) Zinc supplementation reconstitutes the production of interferon-alpha by leukocytes from elderly persons. J Interferon Cytokine Res 17:469–472

    PubMed  CAS  Google Scholar 

  • Casadei M, Persichini T, Polticelli F, Musci G, Colasanti M (2008) S-glutathionylation of metallothioneins by nitrosative/oxidative stress. Exp Gerontol 43:415–422

    PubMed  CAS  Google Scholar 

  • Chernoff R (2005) Micronutrient requirements in older women. Am J Clin Nutr 81:1240S–1245S

    PubMed  CAS  Google Scholar 

  • Chiricolo M, Musa AR, Monti D, Zannotti M, Franceschi C (1993) Enhanced DNA repair in lymphocytes of Down syndrome patients: the influence of zinc nutritional supplementation. Mutat Res 295:105–111

    PubMed  CAS  Google Scholar 

  • Cipriano C, Malavolta M, Costarelli L, Giacconi R, Muti E, Gasparini N, Cardelli M, Monti D, Mariani E, Mocchegiani E (2006) Polymorphisms in MT1a gene with longevity in Italian Central female population. Biogerontology 7:357–365

    PubMed  CAS  Google Scholar 

  • Cipriano C, Tesei S, Malavolta M, Giacconi R, Muti E, Costarelli L, Piacenza F, Pierpaoli S, Galeazzi R, Blasco M, Vera E, Canela A, Lattanzio F, Mocchegiani E (2009) Accumulation of cells with short telomeres is associated with impaired zinc homeostasis and inflammation in old hypertensive participants. J Gerontol A Biol Sci Med Sci 64:745–751

    PubMed  Google Scholar 

  • Clemons TE, Kurinij N, Sperduto RD, AREDS Research Group (2004) Associations of mortality with ocular disorders and an intervention of high-dose antioxidants and zinc in the Age-Related Eye Disease Study: AREDS Report No. 13 Arch Ophthalmol 122:716–726

    Google Scholar 

  • Coneyworth LJ, Mathers JC, Ford D (2009) Does promoter methylation of the SLC30A5 (ZnT5) zinc transporter gene contribute to the ageing-related decline in zinc status? Proc Nutr Soc 68:142–147

    PubMed  CAS  Google Scholar 

  • Costarelli L, Muti E, Malavolta M, Giacconi R, Cipriano C, Sartini D, Emanuelli M, Silvestrini M, Provinciali L, Gobbi B, Mocchegiani E (2008) Modulation of genes involved in zinc homeostasis in old low-grade atherosclerotic patients under effects of HMG-CoA reductase inhibitors. Rejuvenation Res 11:287–291

    PubMed  CAS  Google Scholar 

  • Cousins RJ (1985) Absorption, transport, and hepatic metabolism of copper and zinc: special reference to metallothionein and ceruloplasmin. Physiol Rev 65:238–309

    PubMed  CAS  Google Scholar 

  • Cousins RJ (1996) Zinc. In: Filer LJ, Ziegler EE (eds) Present knowledge in nutrition, 7th edn. International Life Science Institute-Nutrition Foundation, Washington, DC, pp 93–306

    Google Scholar 

  • Cousins RJ (2010) Gastrointestinal factors influencing zinc absorption and homeostasis. Int J Vitam Nutr Res 80:243–248

    PubMed Central  PubMed  CAS  Google Scholar 

  • Cragg RA, Phillips SR, Piper JM, Varma JS, Campbell FC, Mathers JC, Ford D (2005) Regulation of zinc transporters in the human small intestine by dietary zinc supplementation. Gut 54:469–478

    PubMed Central  PubMed  CAS  Google Scholar 

  • Cui J, Shin T, Kawano T, Sato H, Kondo E, Toura I, Kaneko Y, Koseki H, Kanno M, Taniguchi M (1997) Requirement for Valpha14 NKT cells in IL-12-mediated rejection of tumors. Science 278:1623–1626

    PubMed  CAS  Google Scholar 

  • Cunningham-Rundles S, McNeeley DF, Moon A (2005) Mechanisms of nutrient modulation of the immune response. J Allergy Clin Immunol 115:1119–1128

    PubMed  CAS  Google Scholar 

  • Dardenne M (2002) Zinc and immune function. Eur J Clin Nutr 56(Suppl 3):S20–S23

    PubMed  CAS  Google Scholar 

  • Dardenne M, Boukaiba N, Gagnerault MC, Homo-Delarche F, Chappuis P, Lemonnier D, Savino W (1993) Restoration of the thymus in aging mice by in vivo zinc supplementation. Clin Immunol Immunopathol 66:127–135

    PubMed  CAS  Google Scholar 

  • Davis SR, McMahon RJ, Cousins RJ (1998) Metallothionein knockout and transgenic mice exhibit altered intestinal processing of zinc with uniformzinc-dependent zinc transporter-1 expression. J Nutr 128:825–831

    PubMed  CAS  Google Scholar 

  • Drewnowski A, Evans WJ (2001) Nutrition, physical activity, and quality of life in older adults: summary. J Gerontol A Biol Sci Med Sci 56:89–94

    PubMed  Google Scholar 

  • Drewnowski A, Shultz JM (2001) Impact of aging on eating behaviors, food choices, nutrition, and health status. J Nutr Health Aging 5:75–79

    PubMed  CAS  Google Scholar 

  • Driessen C, Hirv K, Rink L, Kirchner H (1994) Induction of cytokines by zinc ions in human peripheral blood mononuclear cells and separated monocytes. Lymphokine Cytokine Res 13:15–20

    PubMed  CAS  Google Scholar 

  • Ducros V, Andriollo-Sanchez M, Arnaud J, Meunier N, Laporte F, Hininger-Favier I, Coudray C, Ferry M, Roussel AM (2009) Zinc supplementation does not alter plasma homocysteine, vitamin B12 and red blood cell folate concentrations in French elderly subjects. J Trace Elem Med Biol 23:15–20

    PubMed  CAS  Google Scholar 

  • Dufner-Beattie J, Wang F, Kuo YM, Gitschier J, Eide D, Andrews GK (2003) The acrodermatitis enteropathica gene ZIP4 encodes a tissue-specific, zinc-regulated zinc transporter in mice. J Biol Chem 278:33474–33481

    PubMed  CAS  Google Scholar 

  • Dufner-Beattie J, Kuo YM, Gitschier J, Andrews GK (2004) The adaptive response to dietary zinc in mice involves the differential cellular localization and zinc regulation of the zinc transporters ZIP4 and ZIP5. J Biol Chem 279:49082–49090

    PubMed  CAS  Google Scholar 

  • Dursun N, Aydoğan S (1994) Comparative effects of calcium deficiency and supplements on the intestinal absorption of zinc in rats. Jpn J Physiol 44:157–166

    PubMed  CAS  Google Scholar 

  • Eberle J, Schindmayer S, Erben RG, Stangassinger M, Roth HP (1999) Skeletal effects of zinc deficiency in growing rats. J Trace Elem Med Biol 13:21–26

    PubMed  CAS  Google Scholar 

  • Eide DJ (2004) The SLC39 family of metal ion transporters. Pflugers Arch 447:796–800

    PubMed  CAS  Google Scholar 

  • Ellis R, Kelsay JL, Reynolds RD, Morris ER, Moser PB, Frazier CW (1987) Phytate:zinc and phytate X calcium:zinc millimolar ratios in self-selected diets of Americans, Asian Indians, and Nepalese. J Am Diet Assoc 87:1043–1047

    PubMed  CAS  Google Scholar 

  • Elmes ME, Jones JG (1980) Ultrastructural changes in the small intestine of zinc deficient rats. J Pathol 130:37–43

    PubMed  CAS  Google Scholar 

  • Emoto M, Kaufmann SH (2003) Liver NKT cells: an account of heterogeneity. Trends Immunol 24:364–369

    PubMed  CAS  Google Scholar 

  • Evans GW (1986) Zinc and its deficiency diseases. Clin Physiol Biochem 4:94–98

    PubMed  CAS  Google Scholar 

  • Fabian E, Elmadfa I (2008) Nutritional situation of the elderly in the European Union: data of the European Nutrition and Health Report (2004). Ann Nutr Metab 52(Suppl 1):57–61

    PubMed  CAS  Google Scholar 

  • Food and Nutrition Board, Institute of Medicine (2001) Zinc. Dietary reference intakes for vitamin A, vitamin K, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. National Academy Press, Washington, DC, pp 442–501

    Google Scholar 

  • Fraker PJ (2005) Roles for cell death in zinc deficiency. J Nutr 135:359–362

    PubMed  CAS  Google Scholar 

  • Fraker PJ, Telford WG (1997) A reappraisal of the role of zinc in life and death decisions of cells. Proc Soc Exp Biol Med 215:229–236

    PubMed  CAS  Google Scholar 

  • Franceschi C (2007) Inflammaging as a major characteristic of old people: can it be prevented or cured? Nutr Rev 65:S173–S176

    PubMed  Google Scholar 

  • Franceschi C, Chiricolo M, Licastro F, Zannotti M, Masi M, Mocchegiani E, Fabris N (1988) Oral zinc supplementation in Down’s syndrome: restoration of thymic endocrine activity and of some immune defects. J Ment Defic Res 32:169–181

    PubMed  Google Scholar 

  • Franceschi C, Olivieri F, Marchegiani F, Cardelli M, Cavallone L, Capri M, Salvioli S, Valensin S, De Benedictis G, Di Iorio A, Caruso C, Paolisso G, Monti D (2005) Genes involved in immune response/inflammation, IGF1/insulin pathway and response to oxidative stress play a major role in the genetics of human longevity: the lesson of centenarians. Mech Ageing Dev 126:351–361

    PubMed  CAS  Google Scholar 

  • Frazzini V, Rockabrand E, Mocchegiani E, Sensi SL (2006) Oxidative stress and brain aging: is zinc the link? Biogerontology 7:307–314

    PubMed  CAS  Google Scholar 

  • Freedman LP, Towers TL (1991) DNA binding properties of the vitamin D3 receptor zinc finger region. Mol Endocrinol 5:1815–1826

    PubMed  CAS  Google Scholar 

  • Gabriel P, Cakman I, Rink L (2002) Overproduction of monokines by leukocytes after stimulation with lipopolysaccharide in the elderly. Exp Gerontol 37:235–247

    PubMed  CAS  Google Scholar 

  • García OP, Long KZ, Rosado JL (2009) Impact of micronutrient deficiencies on obesity. Nutr Rev 67:559–572

    PubMed  Google Scholar 

  • Genser D (2008) Food and drug interaction: consequences for the nutrition/health status. Ann Nutr Metab 52(Suppl 1):29–32

    PubMed  CAS  Google Scholar 

  • Giacconi R, Cipriano C, Albanese F, Boccoli G, Saba V, Olivieri F, Franceschi C, Mocchegiani E (2004) The −174G/C polymorphism of IL-6 is useful to screen old subjects at risk for atherosclerosis or to reach successful ageing. Exp Gerontol 39:621–628

    PubMed  CAS  Google Scholar 

  • Giacconi R, Malavolta M, Costarelli L, Busco F, Galeazzi R, Bernardini G, Gasparini G, Mocchegiani E (2011) Comparison of intracellular zinc signals in non-adherent lymphocytes from young-adult and elderly donors: role of zinc transporters (Zip-family) and pro-inflammatory cytokines. J Nutr Biochem (in press)

  • Gibson RS, Heath AL, Ferguson EL (2002) Risk of suboptimal iron and zinc nutriture among adolescent girls in Australia and New Zealand: causes, consequences, and solutions. Asia Pac J Clin Nutr 11(Suppl 3):S543–S552

    PubMed  CAS  Google Scholar 

  • Gibson RS, Hess SY, Hotz C, Brown KH (2008) Indicators of zinc status at the population level: a review of the evidence. Br J Nutr 99:S14–S23

    PubMed  CAS  Google Scholar 

  • Grahn BH, Paterson PG, Gottschall-Pass KT, Zhang Z (2001) Zinc and the eye. J Am Coll Nutr 20(Suppl 2):106–118

    PubMed  CAS  Google Scholar 

  • Gregg R, Smith CM, Clark FJ, Dunnion D, Khan N, Chakraverty R, Nayak L, Moss PA (2005) The number of human peripheral blood CD4+ CD25 high regulatory T cells increases with age. Clin Exp Immunol 140:540–546

    PubMed Central  PubMed  CAS  Google Scholar 

  • Gunshin H, Mackenzie B, Berger UV, Gunshin Y, Romero MF, Boron WF, Nussberger S, Gollan JL, Hediger MA (1997) Cloning and characterization of a mammalian proton-coupled metal-ion transporter. Nature 388:482–488

    PubMed  CAS  Google Scholar 

  • Gur A, Colpan L, Nas K, Cevik R, Saraç J, Erdoğan F, Düz MZ (2002) The role of trace minerals in the pathogenesis of postmenopausal osteoporosis and a new effect of calcitonin. J Bone Miner Metab 20:39–43

    PubMed  CAS  Google Scholar 

  • Haase H, Rink L (2007) Signal transduction in monocytes: the role of zinc ions. Biometals 20:579–585

    PubMed  CAS  Google Scholar 

  • Haase H, Rink L (2009a) Functional significance of zinc-related signalling pathways in immune cells. Annu Rev Nutr 29:133–152

    PubMed  CAS  Google Scholar 

  • Haase H, Rink L (2009b) The immune system and the impact of zinc during aging. Immun Ageing 6:9–15

    PubMed Central  PubMed  Google Scholar 

  • Haase H, Hebel S, Engelhardt G, Rink L (2006a) Flow cytometric measurement of labile zinc in peripheral blood mononuclear cells. Ann Biochem 352:222–230

    CAS  Google Scholar 

  • Haase H, Mocchegiani E, Rink L (2006b) Correlation between zinc status and immune function in the elderly. Biogerontology 7:421–428

    PubMed  CAS  Google Scholar 

  • Hambidge KM (1992) Zinc and diarrhea. Acta Paediatr Suppl 381:82–86

    PubMed  CAS  Google Scholar 

  • Hambidge KM (2000) Human zinc deficiency. J Nutr 130(Suppl 5S):1344S–1349S

    PubMed  CAS  Google Scholar 

  • Hambidge KM (2010) Micronutrient bioavailability: dietary reference intakes and a future perspective. Am J Clin Nutr 91(Suppl 1):1430S–1432S

    PubMed Central  PubMed  CAS  Google Scholar 

  • High KP (1999) Micronutrient supplementation and immune function in the elderly. Clin Infect Dis 28:717–722

    PubMed  CAS  Google Scholar 

  • Hotz C, Peerson JM, Brown KH (2003) Suggested lower cutoffs of serum zinc concentrations for assessing zinc status: reanalysis of the second National Health and Nutrition Examination Survey data (1976–1980). Am J Clin Nutr 78:756–764

    PubMed  CAS  Google Scholar 

  • Hunt JR, Beiseigel JM (2009) Dietary calcium does not exacerbate phytate inhibition of zinc absorption by women from conventional diets. Am J Clin Nutr 89:839–843

    PubMed  CAS  Google Scholar 

  • Ibs KH, Gabriel P, Rink L (2003) Zinc and the immune system of elderly. Adv Cell Aging Gerontol 13:243–259

    CAS  Google Scholar 

  • Intorre F, Polito A, Andriollo-Sanchez M, Azzini E, Raguzzini A, Toti E, Zaccaria M, Catasta G, Meunier N, Ducros V, O’Connor JM, Coudray C, Roussel AM, Maiani G (2008) Effect of zinc supplementation on vitamin status of middle-aged and older European adults: the ZENITH study. Eur J Clin Nutr 62:1215–1223

    PubMed  CAS  Google Scholar 

  • Kahmann L, Uciechowski P, Warmuth S, Malavolta M, Mocchegiani E, Rink L (2006) Effect of improved zinc status on T helper cell activation and TH1/TH2 ratio in healthy elderly individuals. Biogerontology 7:429–435

    PubMed  CAS  Google Scholar 

  • Kahmann L, Uciechowski P, Warmuth S, Plümäkers B, Gressner AM, Malavolta M, Mocchegiani E, Rink L (2008) Zinc supplementation in the elderly reduces spontaneous inflammatory cytokine release and restores T cell functions. Rejuvenation Res 11:227–237

    PubMed  CAS  Google Scholar 

  • Kanoni S, Dedoussis GV, Herbein G, Fulop T, Varin A, Jajte J, Rink L, Monti D, Mariani E, Malavolta M, Giacconi R, Marcellini F, Mocchegiani E (2010) Assessment of gene-nutrient interactions on inflammatory status of the elderly with the use of a zinc diet score—ZINCAGE study. J Nutr Biochem 21:526–531

    PubMed  CAS  Google Scholar 

  • Karaca Z, Tanriverdi F, Kurtoglu S, Tokalioglu S, Unluhizarci K, Kelestimur F (2007) Pubertal arrest due to Zn deficiency: the effect of zinc supplementation. Hormones (Athens) 6:71–74

    Google Scholar 

  • Kim J, Paik HY, Joung H, Woodhouse LR, King JC (2007) Effect of dietary phytate on zinc homeostasis in young and elderly Korean women. J Am Coll Nutr 26:1–9

    PubMed  CAS  Google Scholar 

  • King LE, Osati-Ashtiani F, Fraker PJ (2002) Apoptosis plays a distinct role in the loss of precursor lymphocytes during zinc deficiency in mice. J Nutr 132:974–979

    PubMed  CAS  Google Scholar 

  • King LE, Frentzel JW, Mann JJ, Fraker PJ (2005) Chronic zinc deficiency in mice disrupted T cell lymphopoiesis and erythropoiesis while B cell lymphopoiesis and myelopoiesis were maintained. J Am Coll Nutr 24:494–502

    PubMed  CAS  Google Scholar 

  • Kogirima M, Kurasawa R, Kubori S, Sarukura N, Nakamori M, Okada S, Kamioka H, Yamamoto S (2007) Ratio of low serum zinc levels in elderly Japanese people living in the central part of Japan. Eur J Clin Nutr 61:375–381

    PubMed  CAS  Google Scholar 

  • Krezel A, Hao Q, Maret W (2007) The zinc/thiolate redox biochemistry of metallothionein and the control of zinc ion fluctuations in cell signaling. Arch Biochem Biophys 463:188–200

    PubMed  CAS  Google Scholar 

  • Kury S, Dreno B, Bezieau S, Giraudet S, Kharfi M, Kamoun R, Moisan JP (2002) Identification of SLC39A4, a gene involved in acrodermatitis enteropathica. Nat Genet 31:239–240

    PubMed  Google Scholar 

  • Lang C, Murgia C, Leong M, Tan LW, Perozzi G, Knight D, Ruffin R, Zalewski P (2007) Anti-inflammatory effects of zinc and alterations in zinc transporter mRNA in mouse models of allergic inflammation. Am J Physiol Lung Cell Mol Physiol 292:L577–L584

    PubMed  CAS  Google Scholar 

  • Lang PO, Michel JP, Zekry D (2009) Frailty syndrome: a transitional state in a dynamic process. Gerontology 55:539–549

    PubMed  Google Scholar 

  • Leek JC, Keen CL, Vogler JB, Golub MS, Hurley LS, Hendrickx AG, Gershwin ME (1988) Long-term marginal zinc deprivation in rhesus monkeys. IV. Effects on skeletal growth and mineralization. Am J Clin Nutr 47:889–895

    PubMed  CAS  Google Scholar 

  • Licastro F, Chiricolo M, Mocchegiani E, Fabris N, Zannoti M, Beltrandi E, Mancini R, Parente R, Arena G, Masi M (1994) Oral zinc supplementation in Down’s syndrome subjects decreased infections and normalized some humoral and cellular immune parameters. J Intellect Disabil Res 38:149–162

    PubMed  Google Scholar 

  • Little KY, Castellanos X, Humphries LL, Austin J (1989) Altered Zn metabolism in mood disordered patients. Biol Psychol 26:646–648

    CAS  Google Scholar 

  • Liuzzi JP, Aydemir F, Nam H, Knutson MD, Cousins RJ (2006) Zip14 (Slc39a14) mediates non-transferrin-bound iron uptake into cells. Proc Natl Acad Sci USA 103:13612–13617

    PubMed Central  PubMed  CAS  Google Scholar 

  • Lonnerdal B (2000) Dietary factors influencing zinc absorption. J Nutr 130:1378S–1383S

    PubMed  CAS  Google Scholar 

  • Lyon CJ, Law RE, Hsueh WA (2003) Minireview: adiposity, inflammation, and atherogenesis. Endocrinology 144:2195–2200

    PubMed  CAS  Google Scholar 

  • Ma J, Betts NM (2000) Zinc and copper intakes and their major food sources for older adults the 1994–96 continuing survey of food intakes by individuals (CSFII). J Nutr 130:2838–2843

    PubMed  CAS  Google Scholar 

  • MacKenzie GG, Zago MP, Aimo L, Oteiza PI (2007) Zinc deficiency in neuronal biology. IUBMB Life 59:299–307

    PubMed  CAS  Google Scholar 

  • Malavolta M, Giacconi R, Piacenza F, Santarelli L, Cipriano C, Costarelli L, Tesei S, Pierpaoli S, Basso A, Galeazzi R, Lattanzio F, Mocchegiani E (2010) Plasma copper/zinc ratio: an inflammatory/nutritional biomarker as predictor of all-cause mortality in elderly population. Biogerontology 11:309–319

    PubMed  CAS  Google Scholar 

  • Marcellini F, Giuli C, Papa R, Gagliardi C, Dedoussis G, Herbein G, Fulop T, Monti D, Rink L, Jajte J, Mocchegiani E (2006) Zinc status, psychological and nutritional assessment in old people recruited in five European countries: ZINCAGE study. Biogerontology 7:339–345

    PubMed  CAS  Google Scholar 

  • Maret W (2003) Cellular zinc and redox states converge in the metallothionein/thionein pair. J Nutr 133(Suppl 1):1460S–1462S

    PubMed  CAS  Google Scholar 

  • Maret W, Sandstead HH (2006) Zinc requirements and the risks and benefits of zinc supplementation. J Trace Elem Med Biol 20:3–18

    PubMed  CAS  Google Scholar 

  • Mariani E, Cattini L, Neri S, Malavolta M, Mocchegiani E, Ravaglia G, Facchini A (2006) Simultaneous evaluation of circulating chemokine and cytokine profiles in elderly subjects by multiplex technology: relationship with zinc status. Biogerontology 7:449–459

    PubMed  CAS  Google Scholar 

  • Mariani E, Neri S, Cattini L, Mocchegiani E, Malavolta M, Dedoussis GV, Kanoni S, Rink L, Jajte J, Facchini A (2008) Effect of zinc supplementation on plasma IL-6 and MCP-1 production and NK cell function in healthy elderly: interactive influence of +647 MT1a and −174 IL-6 polymorphic alleles. Exp Gerontol 43:462–471

    PubMed  CAS  Google Scholar 

  • Markovits PM, Sankey AW, James DK, McCabe R, Mahomed K, Golding J (1990) Zn taste test and postnatal depression. Br J Psychol 156:451–452

    CAS  Google Scholar 

  • Max Rubner-Institut (MRI) (editor) (2008) Nationale Verzehrstudie; Federal Research Institute of Nutrition and Food. Karlsruhe, Germany

  • Mazzatti DJ, Malavolta M, White AJ, Costarelli L, Giacconi R, Muti E, Cipriano C, Powell JR, Mocchegiani E (2007) Differential effects of in vitro zinc treatment on gene expression in peripheral blood mononuclear cells derived from young and elderly individuals. Rejuvenation Res 10:603–620

    PubMed  CAS  Google Scholar 

  • Mazzatti DJ, Malavolta M, White AJ, Costarelli L, Giacconi R, Muti E, Cipriano C, Powell JR, Mocchegiani E (2008) Effects of interleukin-6 −174C/G and metallothionein 1A +647A/C single-nucleotide polymorphisms on zinc-regulated gene expression in ageing. Exp Gerontol 43:423–432

    PubMed  CAS  Google Scholar 

  • McLeod JD (2000) Apoptotic capability in ageing T cells. Mech Ageing Dev 121:151–159

    PubMed  CAS  Google Scholar 

  • McMahon RJ, Cousins RJ (1998) Mammalian zinc transporters. J Nutr 128:667–670

    PubMed  CAS  Google Scholar 

  • Menard MP, Cousins RJ (1983) Zinc transport by brush border membrane vesicles from rat intestine. J Nutr 113:1434–1442

    PubMed  CAS  Google Scholar 

  • Meunier N, Feillet-Coudray C, Rambeau M, Andriollo-Sanchez M, Brandolini-Bunlon M, Coulter SJ, Cashman KD, Mazur A, Coudray C (2005) Impact of micronutrient dietary intake and status on intestinal zinc absorption in late middle-aged men: the ZENITH study. Eur J Clin Nutr 59:S48–S52

    PubMed  CAS  Google Scholar 

  • Mitchell WA, Meng I, Nicholson SA, Aspinall R (2006) Thymic output, ageing and zinc. Biogerontology 7:461–470

    PubMed  CAS  Google Scholar 

  • Miyaji C, Watanabe H, Toma H, Akisaka M, Tomiyama K, Sato Y, Abo T (2000) Functional alteration of granulocytes, NK cells, and natural killer T cells in centenarians. Hum Immunol 61:908–916

    PubMed  CAS  Google Scholar 

  • Mocchegiani E, Santarelli L, Muzzioli M, Fabris N (1995) Reversibility of the thymic involution and of age-related peripheral immune dysfunctions by zinc supplementation in old mice. Int J Immunopharmacol 17:703–718

    PubMed  CAS  Google Scholar 

  • Mocchegiani E, Muzzioli M, Cipriano C, Giacconi R (1998) Zinc, T-cell pathways, aging: role of metallothioneins. Mech Ageing Dev 106:183–204

    PubMed  CAS  Google Scholar 

  • Mocchegiani E, Muzzioli M, Giacconi R (2000) Zinc and immunoresistance to infection in aging: new biological tools. Trends Pharmacol Sci 21:205–208

    PubMed  CAS  Google Scholar 

  • Mocchegiani E, Muzzioli M, Giacconi R, Cipriano C, Gasparini N, Franceschi C, Gaetti R, Cavalieri E, Suzuki H (2003) Metallothioneins/PARP-1/IL-6 interplay on natural killer cell activity in elderly: parallelism with nonagenarians and old infected humans. Effect of zinc supply. Mech Ageing Dev 124:459–468

    PubMed  CAS  Google Scholar 

  • Mocchegiani E, Giacconi R, Cipriano C, Gasparini N, Bernardini G, Malavolta M, Menegazzi M, Cavalieri E, Muzzioli M, Ciampa AR, Suzuki H (2004) The variations during the circadian cycle of liver CD1d-unrestricted NK1.1 + TCR gamma/delta + cells lead to successful ageing. Role of metallothionein/IL-6/gp130/PARP-1 interplay in very old mice. Exp Gerontol 39:775–788

    PubMed  CAS  Google Scholar 

  • Mocchegiani E, Costarelli L, Giacconi R, Cipriano C, Muti E, Tesei S, Malavolta M (2006) Nutrient-gene interaction in ageing and successful ageing. A single nutrient (zinc) and some target genes related to inflammatory/immune response. Mech Ageing Dev 127:517–525

    PubMed  CAS  Google Scholar 

  • Mocchegiani E, Giacconi R, Cipriano C, Costarelli L, Muti E, Tesei S, Giuli C, Papa R, Marcellini F, Mariani E, Rink L, Herbein G, Varin A, Fulop T, Monti D, Jajte J, Dedoussis G, Gonos ES, Trougakos IP, Malavolta M (2007) Zinc, metallothioneins, and longevity—effect of zinc supplementation: ZINCAGE study. Ann NY Acad Sci 1119:129–146

    PubMed  CAS  Google Scholar 

  • Mocchegiani E, Bürkle A, Fulop T (2008a) Zinc and ageing (ZINCAGE project). Exp Gerontol 43:361–362

    PubMed  Google Scholar 

  • Mocchegiani E, Giacconi R, Costarelli L, Muti E, Cipriano C, Tesei S, Pierpaoli S, Giuli C, Papa R, Marcellini F, Gasparini N, Pierandrei R, Piacenza F, Mariani E, Monti D, Dedoussis G, Kanoni S, Herbein G, Fulop T, Rink L, Jajte J, Malavolta M (2008b) Zinc deficiency and IL-6 −174G/C polymorphism in old people from different European countries: effect of zinc supplementation. ZINCAGE study. Exp Gerontol 43:433–444

    PubMed  CAS  Google Scholar 

  • Mocchegiani E, Giacconi R, Malavolta M (2008c) Zinc signalling and subcellular distribution: emerging targets in type 2 diabetes. Trends Mol Med 14:419–428

    PubMed  CAS  Google Scholar 

  • Mocchegiani E, Malavolta M, Muti E, Costarelli L, Cipriano C, Piacenza F, Tesei S, Giacconi R, Lattanzio F (2008d) Zinc, metallothioneins and longevity: interrelationships with niacin and selenium. Curr Pharm Des 14:2719–2732

    PubMed  CAS  Google Scholar 

  • Mocchegiani E, Giacconi R, Cipriano C, Malavolta M (2009) NK and NKT cells in aging and longevity: role of zinc and metallothioneins. J Clin Immunol 29:416–425

    PubMed  CAS  Google Scholar 

  • Mocchegiani E, Malavolta M, Lattanzio F, Piacenza F, Basso A, Abbatecola AM, Russo A, Giovannini S, Capoluongo E, Bustacchini S, Guffanti EE, Bernabei R, Landi F (2011) Cu to Zn ratio, physical function, disability, and mortality risk in older elderly (ilSIRENTE study). AGE (in press)

  • Moroni F, Di Paolo ML, Rigo A, Cipriano C, Giacconi R, Recchioni R, Marcheselli F, Malavolta M, Mocchegiani E (2005) Interrelationship among neutrophil efficiency, inflammation, antioxidant activity and zinc pool in very old age. Biogerontology 6:271–281

    PubMed  CAS  Google Scholar 

  • Mursu J, Robien K, Harnack LJ, Park K, Jacobs DR Jr (2011) Dietary supplements and mortality rate in older women: the Iowa Women’s Health Study. Arch Intern Med 171:1625–1633

    PubMed  CAS  Google Scholar 

  • Muzzioli M, Stecconi R, Moresi R, Provinciali M (2009) Zinc improves the development of human CD34+ cell progenitors towards NK cells and increases the expression of GATA-3 transcription factor in young and old ages. Biogerontology 10:593–604

    PubMed  CAS  Google Scholar 

  • Nasi M, Troiano L, Lugli E, Pinti M, Ferraresi R, Monterastelli E, Mussi C, Salvioli G, Franceschi C, Cossarizza A (2006) Thymic output and functionality of the IL-7/IL-7 receptor system in centenarians: implications for the neolymphogenesis at the limit of human life. Aging Cell 5:167–175

    PubMed  CAS  Google Scholar 

  • Nova E, Lopez-Vidriero I, Varela P, Toro O, Casas JJ, Marcos AA (2004) Indicators of nutritional status in restricting-type anorexia nervosa patients: a 1-year follow-up study. Clin Nutr 23:1353–1359

    PubMed  Google Scholar 

  • Oberleas D, Muhrer ME, O’Dell BL (1966) Dietary metal-complexing agents and zinc availability in the rat. J Nutr 90:56–62

    PubMed  CAS  Google Scholar 

  • Paganelli R, Quinti I, Fagiolo U, Cossarizza A, Ortolani C, Guerra E, Sansoni P, Pucillo LP, Scala E, Cozzi E, Bertollo L, Monti D, Franceschi C (1992) Changes in circulating B cells and immunoglobulin classes and subclasses in healthy aged population. Clin Exp Immunol 90:351–354

    PubMed Central  PubMed  CAS  Google Scholar 

  • Palmiter RD, Findley SD (1995) Cloning and functional characterization of a mammalian zinc transporter that confers resistance to zinc. EMBO J 14:639–649

    PubMed Central  PubMed  CAS  Google Scholar 

  • Palmiter RD, Huang L (2004) Efflux and compartmentalization of zinc by members of the SLC30 family of solute carriers. Pflugers Arch 447:744–751

    PubMed  CAS  Google Scholar 

  • Pawelec G, Remarque E, Barnett Y, Solana R (1998) T cells and aging. Front Biosci 3:d59–d99

    PubMed  CAS  Google Scholar 

  • Pawelec G, Larbi A, Derhovanessian E (2010) Senescence of the human immune system. J Comp Pathol 142(Suppl 1):S39–S44

    PubMed  CAS  Google Scholar 

  • Prasad AS (1985) Clinical, endocrinological and biochemical effects of zinc deficiency. Clin Endocrinol Metab 14:567–589

    PubMed  CAS  Google Scholar 

  • Prasad AS (1998) Zinc and immunity. Mol Cell Biochem 188:63–69

    PubMed  CAS  Google Scholar 

  • Prasad AS (2000) Effects of zinc deficiency on Th1 and Th2 cytokine shifts. J Infect Dis 182:62–68

    Google Scholar 

  • Prasad AS (2007) Zinc: Mechanisms of Host Defense. J Nutr 137:1345–1349

    PubMed  CAS  Google Scholar 

  • Prasad AS (2008) Zinc in human health: effect of zinc on immune cells. Mol Med 14:353–357

    PubMed Central  PubMed  CAS  Google Scholar 

  • Prasad AS (2009) Impact of the discovery of human zinc deficiency on health. J Am Coll Nutr 28:257–265

    PubMed  CAS  Google Scholar 

  • Prasad AS, Fitzgerald JT, Hess JW, Kaplan J, Pelen F, Dardenne M (1993) Zinc deficiency in elderly patients. Nutrition 9:218–224

    PubMed  CAS  Google Scholar 

  • Prasad AS, Bao B, Beck FW, Sarkar FH (2006) Correction of interleukin-2 gene expression by in vitro zinc addition to mononuclear cells from zinc-deficient human subjects: a specific test for zinc deficiency in humans. Transl Res 148:325–333

    PubMed  CAS  Google Scholar 

  • Prasad AS, Beck FW, Bao B, Fitzgerald JT, Snell DC, Steinberg JD, Cardozo LJ (2007) Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress. Am J Clin Nutr 85:837–844

    PubMed  CAS  Google Scholar 

  • Prasad AS, Bao B, Beck FW, Sarkar FH (2011) Zinc-suppressed inflammatory cytokines by induction of A20-mediated inhibition of nuclear factor-κB. Nutrition 27:816–823

    PubMed  CAS  Google Scholar 

  • Provinciali M, Di Stefano G, Stronati S (1998a) Flow cytometric analysis of CD3/TCR complex, zinc, and glucocorticoid-mediated regulation of apoptosis and cell cycle distribution in thymocytes from old mice. Cytometry 32:1–8

    PubMed  CAS  Google Scholar 

  • Provinciali M, Montenovo A, Di Stefano G, Colombo M, Daghetta L, Cairati M, Veroni C, Cassino R, Della Torre F, Fabris N (1998b) Effect of zinc or zinc plus arginine supplementation on antibody titre and lymphocyte subsets after influenza vaccination in elderly subjects: a randomized controlled trial. Age Ageing 27:715–722

    PubMed  CAS  Google Scholar 

  • Rea IM, Ross OA, Armstrong M, McNerlan S, Alexander DH, Curran MD, Middleton D (2003) Interleukin-6-gene C/G 174 polymorphism in nonagenarian and octogenarian subjects in the BELFAST study. Reciprocal effects on IL-6, soluble IL-6 receptor and for IL-10 in serum and monocyte supernatants. Mech Ageing Dev 124:555–561

    PubMed  CAS  Google Scholar 

  • Saba I, Kosan C, Vassen L, Möröy T (2011) IL-7R-dependent survival and differentiation of early T-lineage progenitors is regulated by the BTB/POZ domain transcription factor Miz-1. Blood 117:3370–3381

    PubMed  CAS  Google Scholar 

  • Sandstead HH (1994) Understanding zinc: recent observations and interpretations. J Lab Clin Med 124:322–327

    PubMed  CAS  Google Scholar 

  • Sandstead HH (1995) Requirements and toxicity of essential trace elements, illustrated by zinc and copper. Am J Clin Nutr 61:S621–S624

    Google Scholar 

  • Sandstead HH (2000) Causes of iron and zinc deficiencies and their effects on brain. J Nutr 130(Suppl 2S):347S–349S

    PubMed  CAS  Google Scholar 

  • Sandström B (1992) Dose dependence of zinc and manganese absorption in man. Proc Nutr Soc 51:211–218

    PubMed  Google Scholar 

  • Sandström B (2001) Micronutrient interactions: effects on absorption and bioavailability. Br J Nutr 85(Suppl 2):S181–S185

    PubMed  Google Scholar 

  • Sandström B, Cederblad Å (1980) Zinc absorption from composite meals. II. Influence of the main protein source. Am J Clin Nutr 33:1778–1783

    PubMed  Google Scholar 

  • Sandstrom B, Davidsson L, Cederblad L, Lonnerdal B (1985) Oral iron, dietary ligands and zinc absorption. J Nutr 115:411–414

    PubMed  CAS  Google Scholar 

  • Sato M, Yanagisawa H, Nojima Y, Tamura J, Wada O (2002) Zn deficiency aggravates hypertension in spontaneously hypertensive rats: possible role of Cu/Zn-superoxide dismutase. Clin Exp Hypertens 24:355–370

    PubMed  CAS  Google Scholar 

  • Sayeg Porto MA, Oliveira HP, Cunha AJ, Miranda G, Guimarães MM, Oliveira WA, dos Santos DM (2000) Linear growth and zinc supplementation in children with short stature. J Pediatr Endocrinol Metab 13:1121–1128

    PubMed  CAS  Google Scholar 

  • Sbarbati A, Mocchegiani E, Marzola P, Tibaldi A, Mannucci R, Nicolato E, Osculati F (1998) Effect of dietary supplementation with zinc sulphate on the aging process: a study using high field intensity MRI and chemical shift imaging. Biomed Pharmacother 52:454–458

    PubMed  CAS  Google Scholar 

  • Schroder AK, Rink L (2003) Neutrophil immunity of the elderly. Mech Ageing Dev 124:419–425

    PubMed  Google Scholar 

  • Scientific Committee on Food (SCF) (2002) Opinion of the scientific committee on food on the tolerable upper intake level of zinc. Brussels, Belgium, pp. 15–25

  • Shankar AH, Prasad AS (1998) Zn and immune function: the biological basis of altered resistance to infection. Am J Clin Nutr 68:447S–463S

    PubMed  CAS  Google Scholar 

  • Sladek R, Rocheleau G, Rung J, Dina C, Shen L, Serre D, Boutin P, Vincent D, Belisle A, Hadjadj S, Balkau B, Heude B, Charpentier G, Hudson TJ, Montpetit A, Pshezhetsky AV, Prentki M, Posner BI, Balding DJ, Meyre D, Polychronakos C, Froguel P (2007) A genome-wide association study identifies novel risk loci for type 2 diabetes. Nature 445:881–885

    PubMed  CAS  Google Scholar 

  • Smith JC Jr (1980) The vitamin A-zinc connection: a review. Ann NY Acad Sci 355:62–75

    PubMed  CAS  Google Scholar 

  • Sofi F, Abbate R, Gensini GF, Casini A (2010) Accruing evidence on benefits of adherence to the Mediterranean diet on health: an updated systematic review and meta-analysis. Am J Clin Nutr 92:1189–1196

    PubMed  CAS  Google Scholar 

  • Solana R, Mariani E (2000) NK and NK/T cells in human senescence. Vaccine 18:1613–1620

    PubMed  CAS  Google Scholar 

  • Song MK, Adham NF (1978) Role of prostaglandin E2 in zinc absorption in the rat. Am J Physiol 234:E99–E105

    PubMed  CAS  Google Scholar 

  • Starling RD, Poehlman ET (2000) Assessment of energy requirements in elderly populations. Eur J Clin Nutr 54(Suppl 3):S104–S111

    PubMed  Google Scholar 

  • Steel L, Cousins RJ (1985) Kinetics of zinc absorption by luminally and vascularly perfused rat intestine. Am J Physiol 248:G46–G53

    PubMed  CAS  Google Scholar 

  • Stewart-Knox BJ, Simpson EE, Parr H, Parr H, Rae G, Polito A, Intorre F, Meunier N, Andriollo-Sanchez M, O’Connor JM, Coudray C, Strain JJ (2005) Zinc status and taste acuity in older Europeans: the ZENITH study. Eur J Clin Nutr 59:S31–S36

    PubMed  CAS  Google Scholar 

  • Su JC, Birmingham CL (2002) Zn supplementation in the treatment of anorexia nervosa. Eat Weight Disord 7:20–22

    PubMed  CAS  Google Scholar 

  • Sweeney MP, Bagg J, Fell GS, Yip B (1994) The relationship between micronutrient depletion and oral health in geriatrics. J Oral Pathol Med 23:168–171

    PubMed  CAS  Google Scholar 

  • Swoboda JR, Kiyak HA, Darveau R, Persson GR (2008) Correlates of periodontal decline and biologic markers in older adults. J Periodontol 79:1920–1926

    PubMed  Google Scholar 

  • Tallkvist J, Bowlus CL, Lönnerdal B (2000) Functional and molecular responses of human intestinal Caco-2 cells to iron treatment. Am J Clin Nutr 72:770–775

    PubMed  CAS  Google Scholar 

  • Taub DD, Longo DL (2005) Insights into thymic aging and regeneration. Immunol Rev 205:72–93

    PubMed  CAS  Google Scholar 

  • Taysi S, Cikman O, Kaya A, Demircan B, Gumustekin K, Yilmaz A, Boyuk A, Keles M, Akyuz M, Turkeli M (2008) Increased oxidant stress and decreased antioxidant status in erythrocytes of rats fed with zinc-deficient diet. Biol Trace Elem Res 123:161–167

    PubMed  CAS  Google Scholar 

  • Thomson AB (2009) Small intestinal disorders in the elderly. Best Pract Res Clin Gastroenterol 23:861–874

    PubMed  Google Scholar 

  • Tinker D, Rucker RB (1985) Role of selected nutrients in synthesis, accumulation, and chemical modification of connective tissue proteins. Physiol Rev 65:607–657

    PubMed  CAS  Google Scholar 

  • Toniato E, Chen XP, Losman J, Flati V, Donahue L, Rothman P (2002) TRIM8/GERP RING finger protein interacts with SOCS-1. J Biol Chem 277:37315–37322

    PubMed  CAS  Google Scholar 

  • Topinková E (2008) Aging, disability and frailty. Ann Nutr Metab 52(Suppl 1):6–11

    PubMed  Google Scholar 

  • Turnlund JR, Michel MC, Keyes WR, King JC, Margen S (1982) Use of enriched stable isotopes to determine zinc and iron absorption in elderly men. Am J Clin Nutr 35:1033–1040

    PubMed  CAS  Google Scholar 

  • U.S. Department of Agriculture (1996) CSFII/DHKS 1994–1996 data set and documentation: the 1994 continuing survey of food intakes by individuals and the 1994–1996 diet and health knowledge survey. On: CSFII/DHKS 1994–96 CD-ROM. Agricultural Research Service, Riverdale, MD

    Google Scholar 

  • Uciechowski P, Kahmann L, Plumakers B, Malavolta M, Mocchegiani E, Dedoussis G, Herbein G, Jajte J, Fulop T, Rink L (2008) TH1 and TH2 cell polarization increases with aging and is modulated by zinc supplementation. Exp Gerontol 43:493–498

    PubMed  CAS  Google Scholar 

  • van der Putten GJ, Vanobbergen J, De Visschere L, Schols J, de Baat C (2009) Association of some specific nutrient deficiencies with periodontal disease in elderly people: a systematic literature review. Nutrition 25:717–722

    PubMed  Google Scholar 

  • Varela P, Marcos A, Navarro MP (1992) Zinc status in anorexia nervosa. Ann Nutr Metab 36:197–202

    PubMed  CAS  Google Scholar 

  • Varin A, Larbi A, Dedoussis GV, Kanoni S, Jajte J, Rink L, Monti D, Malavolta M, Marcellini F, Mocchegiani E, Herbein G, Fulop T Jr (2008) In vitro and in vivo effects of zinc on cytokine signalling in human T cells. Exp Gerontol 43:472–482

    PubMed  CAS  Google Scholar 

  • Vasto S, Mocchegiani E, Candore G, Listì F, Colonna-Romano G, Lio D, Malavolta M, Giacconi R, Cipriano C, Caruso C (2006) Inflammation, genes and zinc in ageing and age-related diseases. Biogerontology 7:315–327

    PubMed  CAS  Google Scholar 

  • Villarino Rodríguez A, García-Linares MC, García-Fernández MC, García-Arias MT (2003) Evaluation of diet and biochemical parameters for minerals in a group of elderly subjects in the province of Leon (Spain). Nutr Hosp 18:39–45

    PubMed  Google Scholar 

  • Volkert D, Kreuel K, Heseker H, Stehle P (2004) Energy and nutrient intake of young-old, old-old and very-old elderly in Germany. Eur J Clin Nutr 58:1190–1200

    PubMed  CAS  Google Scholar 

  • von Bulow V, Rink L, Haase H (2005) Zinc-mediated inhibition of cyclic nucleotide phosphodiesterase activity and expression suppresses TNF-alpha and IL-1 beta production in monocytes by elevation of guanosine 3′,5′-cyclic monophosphate. J Immunol 175:4697–4705

    Google Scholar 

  • Wang X, Zhou B (2010) Dietary zinc absorption: a play of Zips and ZnTs in the gut. IUBMB Life 62:176–182

    PubMed  CAS  Google Scholar 

  • Weksler ME, Szabo P (2000) The effect of age on the B-cell repertoire. J Clin Immunol 20:240–249

    PubMed  CAS  Google Scholar 

  • Whitney AR, Diehn M, Popper SJ, Alizadeh AA, Boldrick JC, Relman DA, Brown PO (2003) Individuality and variation in gene expression patterns in human blood. Proc Natl Acad Sci USA 100:1896–1901

    PubMed Central  PubMed  CAS  Google Scholar 

  • Whittaker P (1998) Iron and zinc interactions in humans. Am J Clin Nutr 68(2 Suppl):442S–446S

    PubMed  CAS  Google Scholar 

  • Wood RJ, Zheng JJ (1997) High dietary calcium intakes reduce zinc absorption and balance in humans. Am J Clin Nutr 65:1803–1809

    PubMed  CAS  Google Scholar 

  • Yu YY, Kirschke CP, Huang L (2007) Immunohistochemical analysis of ZnT1, 4, 5, 6, and 7 in the mouse gastrointestinal tract. J Histochem Cytochem 55:223–234

    PubMed  CAS  Google Scholar 

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Acknowledgements

This study was supported by unrestricted educational grant from Danone, by INRCA, Cariverona Foundation (Italy) and ZINCAGE European Project (n. FOOD-2004-506850; Coordinator: Eugenio Mocchegiani).

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Authors and Affiliations

  1. Ctr. Nutrition and Ageing, Italian National Research Centres on Ageing (INRCA), Via Birarelli 8, 60121, Ancona, Italy

    Eugenio Mocchegiani, Marco Malavolta, Laura Costarelli & Robertina Giacconi

  2. Immunonutrition Research Group, Department of Metabolism and Nutrition, Institute of Food Science and Technology and Nutrition (ICTAN-CSIC), Madrid, Spain

    Javier Romeo, Ligia-Esperanza Diaz & Ascension Marcos

Authors
  1. Eugenio Mocchegiani
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  2. Javier Romeo
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  3. Marco Malavolta
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  4. Laura Costarelli
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  5. Robertina Giacconi
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Correspondence to Eugenio Mocchegiani.

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Javier Romeo passed away 8 August 2011. This manuscript is dedicated to his memory.

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Mocchegiani, E., Romeo, J., Malavolta, M. et al. Zinc: dietary intake and impact of supplementation on immune function in elderly. AGE 35, 839–860 (2013). https://doi.org/10.1007/s11357-011-9377-3

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