Advertisement

Role of Zinc and Selenium in Oxidative Stress and Immunosenescence: Implications for Healthy Ageing and Longevity

  • Eugenio Mocchegiani
  • Marco Malavolta

Abstract

Ageing is an inevitable biological process with gradual and spontaneous biochemical and physiological changes and increased susceptibility to diseases. Some nutritional factors (zinc and selenium) may remodel these changes leading to a possible escaping of diseases with subsequent healthy ageing, because they are especially involved in improving immune functions as well as antioxidant defense. Experiments performed “in vitro” (human lymphocytes exposed to endotoxins) and “in vivo” (old mice or young mice fed with low zinc dietary intake) show that zinc is important for immune response both innate and adoptive. Selenium provokes zinc release by Metallothioneins (MT), via reduction of glutathione peroxidase. This fact is crucial in ageing because high MT may be unable to release zinc with subsequent low intracellular free zinc ion availability for immune response. Taking into account the existence of zinc transporters (ZnT and ZIP family) for cellular zinc efflux and influx, respectively, the association between ZnT and MT is important in maintaining satisfactory intracellular zinc homeostasis in ageing. Improved immune performance occur in elderly after physiological zinc supplementation, which also induces prolonged survival in old, nude and neonatal thymectomized mice. The association “zinc plus selenium” improves humoral immunity in old subjects after influenza vaccination. Therefore, zinc and selenium are relevant for immunosenescence in order to achieve healthy ageing and longevity.

Keywords

Zinc Deficiency Zinc Supplementation Selenium Deficiency Zinc Transporter Selenium Status 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Abo T, Kawamura T Watanabe H (2000) Physiological responses of extrathymic T cells in the liver. Immunol Rev 174:135–149PubMedCrossRefGoogle Scholar
  2. Akbaraly NT, Arnaud J, Hininger-Favier I et al (2005) Selenium and mortality in the elderly:results from the EVA study. Clin Chem 51:2117–2123PubMedCrossRefGoogle Scholar
  3. Alissa EM, Bahijri SM, Ferns GA (2003) The controversy surrounding selenium and cardiovascular disease:a review of the evidence. Med Sci Monit 9:RA9–RA18PubMedGoogle Scholar
  4. Ames BN (2006) Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage. Proc Natl Acad Sci U S A 103:17589–17594PubMedCrossRefGoogle Scholar
  5. Andree KB, Kim J, Kirschke CP et al Investigation of lymphocyte gene expression for use as biomarkers for zinc status in humans. J Nutr 134:1716–1723Google Scholar
  6. Arizono K, Kagawa S, Hamada H et al (1995) Nitric oxide mediated metallothionein induction by lipopolysaccharide. Res Commun Mol Pathol Pharmacol 90:49–58PubMedGoogle Scholar
  7. Arner ES, Holmgren A (2000) Physiological functions of thioredoxin and thioredoxin reductase. Eur J Biochem 267:6102–6109PubMedCrossRefGoogle Scholar
  8. Aro A, Alfthan G, Varo P (1995) Effect of supplementation of fertilizers on human selenium status in Finland. Analyst 120:841–843PubMedCrossRefGoogle Scholar
  9. Arthur JR (2003a) Selenium supplementation:does soil supplementation help and why? Proc Nutr Soc 62:393–397CrossRefGoogle Scholar
  10. Arthur JR, McKenzie RC, Beckett GJ (2003b) Selenium in the immune system. J Nutr 133 (Suppl 1):1457S–1459SGoogle Scholar
  11. Arvin AM (1996) Varicella-zoster virus. Clin Microbiol Rev 9:361–381PubMedGoogle Scholar
  12. Ashok BT, Ali R (1999) The aging paradox:free radical theory of aging. Exp Gerontol 34:293–303PubMedCrossRefGoogle Scholar
  13. Assmann A, Briviba K, Sies H (1998) Reduction of methionine selenoxide to selenomethionine by glutathione. Arch Biochem Biophys 349:201–203PubMedCrossRefGoogle Scholar
  14. Barsyte D, Lovejoy DA, Lithgow GJ (2001) Longevity and heavy metal resistance in daf-2 and age-1 long-lived mutants of Caenorhabditis elegans. FASEB J 15:627–634PubMedCrossRefGoogle Scholar
  15. Bauer JH, Helfand SL (2006) New tricks of an old molecule:lifespan regulation by p53. Aging Cell 5:437–440PubMedCrossRefGoogle Scholar
  16. Beck MA (1999) Selenium and host defence towards viruses. Proc Nutr Soc 58:707–711PubMedGoogle Scholar
  17. Beck MA, Levander OA (2000) Host nutritional status and its effect on a viral pathogen. J Infect Dis 182:S93–S96PubMedCrossRefGoogle Scholar
  18. Beck MA, Levander OA, Handy J (2003) Selenium deficiency and viral infection. J Nutr 133:1463S–1467SPubMedGoogle Scholar
  19. Beckett GJ, Arthur JR (2005) Selenium and endocrine systems. J Endocrinol 184:455–465PubMedCrossRefGoogle Scholar
  20. Beckett GJ, Arthur JR, Miller SM et al (2003) Selenium Immunity and disease. In:Hughes DA, Bendick A, Darlington G (eds) Dietary enhancement of human immune functions. Humana Press, Totowa New Jersy, pp 250–280Google Scholar
  21. Beilstein MA, Whanger PD (1986) Deposition of dietary organic and inorganic selenium in rat erythrocyte proteins. J Nutr 116:1701–1710PubMedGoogle Scholar
  22. Berg JM, Shi Y (1996) The galvanization of biology:a growing appreciation for the roles of zinc. Science 271:1081–1085PubMedCrossRefGoogle Scholar
  23. Bhaskaram P (2002) Micronutrient malnutrition, infection, and immunity:an overview. Nutr Rev 60:S40–S45PubMedCrossRefGoogle Scholar
  24. Bjornstedt M, Hamberg M, Kumar S et al (1995) Human thioredoxin reductase directly reduces lipid hydroperoxides by NADPH and selenocystine strongly stimulates the reaction via catalytically generated selenols. J Biol Chem 270:11761–11764PubMedCrossRefGoogle Scholar
  25. Blot WJ, Li JY, Taylor PR et al (1995) The Linxian trials:mortality rates by vitamin-mineral intervention group. Am J Clin Nutr 62:1424S–1426SPubMedGoogle Scholar
  26. Bogdan C, Rollinghoff M, Diefenbach A (2000) The role of nitric oxide in innate immunity. Immunol Rev 173:17–26PubMedCrossRefGoogle Scholar
  27. Bogden JD, Oleske JM, Lavenhar MA et al (1990) Effects of one year of supplementation with zinc and other micronutrients on cellular immunity in the elderly. J Am Coll Nutr 9:214–225PubMedGoogle Scholar
  28. Boukaiba N, Flament C, Acher S et al (1993) A physiological amount of zinc supplementation:effects on nutritional, lipid, and thymic status in an elderly population. Am J Clin Nutr 57:566–572PubMedGoogle Scholar
  29. Bravo J, Heath JK (2000) Receptor recognition by gp130 cytokines. EMBO J 19:2399–2411PubMedCrossRefGoogle Scholar
  30. Brigelius-Flohe R (1999) Tissue-specific functions of individual glutathione peroxidases. Free Radic Biol Med 27:951–965PubMedCrossRefGoogle Scholar
  31. Bui LM, Dressendorfer RH, Keen CL et al (1994) Zinc status and interleukin-1 beta-induced alterations in mineral metabolism in rats. Proc Soc Exp Biol Med 206:438–444PubMedGoogle Scholar
  32. Burk RF, Hill KE, Motley AK (2003) Selenoprotein metabolism and function:evidence for more than one function for selenoprotein P. J Nutr 133(Suppl 1):1517S–1520SPubMedGoogle Scholar
  33. Buttriss J (2000) Nutrient requirements and optimisation of intakes. Br Med Bull 56:18–33PubMedCrossRefGoogle Scholar
  34. Cai L, Satoh M, Tohyama C et al (1999) Metallothionein in radiation exposure:its induction and protective role. Toxicology 132:85–98PubMedCrossRefGoogle Scholar
  35. Cakman I, Kirchner H, Rink L (1997) Zinc supplementation reconstitutes the production of interferon- alpha by leukocytes from elderly persons. J Interferon Cytokine Res 17:469–472PubMedCrossRefGoogle Scholar
  36. Chernoff R (2001) Nutrition and health promotion in older adults. J Gerontol A Biol Sci Med Sci 56:47–53PubMedGoogle Scholar
  37. Chiricolo M, Musa AR, Monti D et al (1993) Enhanced DNA repair in lymphocytes of Down syndrome patients:the influence of zinc nutritional supplementation. Mutat Res 295:105–111PubMedGoogle Scholar
  38. Cipriano C, Malavolta M, Costarelli L et al (2006) Polymorphisms in MT1a gene coding region are associated with longevity in Italian Central female population. Biogerontology 7:357–365PubMedCrossRefGoogle Scholar
  39. Clegg MS, Hanna LA, Niles BJ et al (2005) Zinc deficiency-induced cell death. IUBMB Life 57:661–669PubMedCrossRefGoogle Scholar
  40. Clark LC, Dalkin B, Krongrad A et al (1998) Decreased incidence of prostate cancer with selenium supplementation:results of a double-blind cancer prevention trial. Br J Urol 81:730–734PubMedGoogle Scholar
  41. Clifford KS, MacDonald MJ (2000) Survey of mRNAs encoding zinc transporters and other metal complexing proteins in pancreatic islets of rats from birth to adulthood:similar patterns in the Sprague-Dawley and Wistar BB strains. Diabetes Res Clin Pract 49:77–85PubMedCrossRefGoogle Scholar
  42. Coodley G (1995) Update on vitamins, minerals, and the carotenoids. J Physicians Assoc AIDS Care 2:24–29PubMedGoogle Scholar
  43. Colasanti M, Suzuki H (2000) The dual personality of NO. Trends Pharmacol Sci 21:249–252PubMedCrossRefGoogle Scholar
  44. Coleman JE (1992) Zinc proteins:enzymes, storage proteins, transcription factors, and replication proteins. Annu Rev Biochem 61:897–946PubMedCrossRefGoogle Scholar
  45. Colonna-Romano G, Potestio M, Aquino A et al (2002) Gamma/delta T lymphocytes are affected in the elderly. Exp Gerontol 3:7205–7211Google Scholar
  46. Combs GF Jr (2001) Impact of selenium and cancer-prevention findings on the nutrition-health paradigm. Nutr Cancer 40:6–11PubMedCrossRefGoogle Scholar
  47. Coto JA, Hadden EM, Sauro M et al (1992) Interleukin 1 regulates secretion of zinc-thymulin by human thymic epithelial cells and its action on T-lymphocyte proliferation and nuclear protein kinase C. Proc Natl Acad Sci U S A 89:7752–7756PubMedCrossRefGoogle Scholar
  48. Cousins RJ, McMahon RJ (2000) Integrative aspects of zinc transporters. J Nutr 130(Suppl 5):1384S–1387SPubMedGoogle Scholar
  49. Czernichow S, Bertrais S, Blacher J et al (2005) Effect of supplementation with antioxidants upon long-term risk of hypertension in the SU.VI.MAX study:association with plasma antioxidant levels. J Hypertens 23:2013–2018PubMedCrossRefGoogle Scholar
  50. Dangour AD, Sibson VL, Fletcher AE (2004) Micronutrient supplementation in later life:limited evidence for benefit. J Gerontol A Biol Sci Med Sci 59:659–673PubMedGoogle Scholar
  51. Daniels LA (2004) Selenium:does selenium status have health outcomes beyond overt deficiency? Med J Aust 180:373–374PubMedGoogle Scholar
  52. Dardenne M, Boukaiba N, Gagnerault MC et al (1993) Restoration of the thymus in aging mice by in vivo zinc supplementation. Clin Immunol Immunopathol 66:127–135PubMedCrossRefGoogle Scholar
  53. Das KC, Das CK (2000) Thioredoxin, a singlet oxygen quencher and hydroxyl radical scavenger:redox independent functions. Biochem Biophys Res Commun 277:443–447PubMedCrossRefGoogle Scholar
  54. DeGroot DW, Havenith G, Kenney WL (2006) Responses to mild cold stress are predicted by different individual characteristics in young and older subjects. J Appl Physiol 101:1607–1615PubMedCrossRefGoogle Scholar
  55. Delmas-Beauvieux MC, Peuchant E et al (1996) The enzymatic antioxidant system in blood and glutathione status in human immunodeficiency virus (HIV)-infected patients:effects of supplementation with selenium or beta-carotene. Am J Clin Nutr 64:101–107PubMedGoogle Scholar
  56. Driessen C, Hirv K, Rink L et al (1994) Induction of cytokines by zinc ions in human peripheral blood mononuclear cells and separated monocytes. Lymphokine Cytokine Res 13:15–20PubMedGoogle Scholar
  57. Duarte EA, Novella IS, Weaver SC et al (1994) RNA virus quasispecies:significance for viral disease and epidemiology. Infect Agents Dis 3:201–214PubMedGoogle Scholar
  58. Duchateau J (2004) Immunosenescence and the lung. Rev Mal Respir 21:8S81–8S87PubMedGoogle Scholar
  59. Duchateau J, Delepesse G, Vrijens R et al (1981) Beneficial effects of oral zinc supplementation on the immune response of old people. Am J Med 70:1001–1004PubMedCrossRefGoogle Scholar
  60. Ebadi M, Swanson S (1988) The status of zinc, copper, and metallothionein in cancer patients. Prog Clin Biol Res 259:161–175PubMedGoogle Scholar
  61. Eide DJ (2006) Zinc transporters and the cellular trafficking of zinc. Biochem Biophys Acta 1763:711–722PubMedCrossRefGoogle Scholar
  62. Ellis SE, Coffey CS, Mitchel EF Jr et al (2003) Influenza- and respiratory syncytial virus-associated morbidity and mortality in the nursing home population. J Am Geriatr Soc 51:761–767PubMedCrossRefGoogle Scholar
  63. Enwonwu CO, Sanders C (2001) Nutrition:impact on oral and systemic health. Compend Contin Educ Dent 22:12–18PubMedGoogle Scholar
  64. Fabris N, Mocchegiani E (1995) Zinc, human diseases and aging. Aging 7:77–93PubMedGoogle Scholar
  65. Fabris N, Mocchegiani E, Amadio L et al (1984) Thymic hormone deficiency in normal ageing and Down’s syndrome:is there a primary failure of the thymus? Lancet 1:983–986PubMedCrossRefGoogle Scholar
  66. Feillet-Coudray C, Meunier N, Bayle D et al (2006) Effect of zinc supplementation on in vitro copper-induced oxidation of low-density lipoproteins in healthy French subjects aged 55–70 years:the Zenith Study. Br J Nutr 95:1134–1142PubMedCrossRefGoogle Scholar
  67. Feng W, Benz FW, Cai J et al (2006) Metallothionein disulfides are present in metallothioneinoverexpressing transgenic mouse heart and increase under conditions of oxidative stress. J Biol Chem 281:681–687PubMedCrossRefGoogle Scholar
  68. Feng W, Cai J, Pierce WM et al (2005) Metallothionein transfers zinc to mitochondrial aconitase through a direct interaction in mouse hearts. Biochem Biophys Res Commun 332:853–858PubMedCrossRefGoogle Scholar
  69. Forceville X, Vitoux D, Gauzit R et al (1998) Selenium, systemic immune response syndrome, sepsis, and outcome in critically ill patients. Crit Care Med 26:1536–1544PubMedCrossRefGoogle Scholar
  70. Fortes C, Agabiti N, Fano V et al (1997) Zinc supplementation and plasma lipid peroxides in an elderly population. Eur J Clin Nutr 51:97–101PubMedCrossRefGoogle Scholar
  71. Fortes C, Forestiere F, Agabiti N et al (1998) The effect of zinc and vitamin A supplementation on immune response in an older population. J Am Geriatr Soc 46:19–26PubMedGoogle Scholar
  72. Fosmire GJ (1990) Zinc toxicity. Am J Clin Nutr 51:225–227PubMedGoogle Scholar
  73. Fraker PJ (2005) Roles for cell death in zinc deficiency. J Nutr 135:359–362PubMedGoogle Scholar
  74. Fraker PJ, Lill-Elghanian DA (2004) The many roles of apoptosis in immunity as modified by aging and nutritional status. J Nutr Health Aging 8:56–63PubMedGoogle Scholar
  75. Franceschi C, Bonafe M, Valensin S et al (2000) Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci 908:244–254PubMedGoogle Scholar
  76. Franceschi C, Chiricolo M, Licastro F et al (1988) Oral zinc supplementation in Down’s syndrome:restoration of thymic endocrine activity and of some immune defects. J Ment Defic Res 32:169–181PubMedGoogle Scholar
  77. Franceschi C, Olivieri F, Marchegiani F et al (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 126:351–361PubMedCrossRefGoogle Scholar
  78. Ghyselinck NB, Dufaure I, Lareyre JJ et al (1993) Structural organization and regulation of the gene for the androgen-dependent glutathione peroxidase-like protein specific to the mouse epididymis. Mol Endocrinol 7:258–272PubMedCrossRefGoogle Scholar
  79. Giacconi R, Cipriano C, Muti E et al (2005) Novel -209A/G MT2A Polymorphism in old patients with Type 2 diabetes and atherosclerosis:Relationship with inflammation (IL-6) and Zinc. Biogerontology 6:407–413PubMedCrossRefGoogle Scholar
  80. Girodon F, Galan P, Monget AL et al (1999) Impact of trace elements and vitamin supplementation on immunity and infections in institutionalized elderly patients:a randomized controlled trial. MIN. VIT. AOX. geriatric network. Arch Intern Med 159:748–754PubMedCrossRefGoogle Scholar
  81. Gueders MM, Foidart JM, Noel A et al (2006) Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs in the respiratory tract:potential implications in asthma and other lung diseases. Eur J Pharmacol 533:133–144PubMedCrossRefGoogle Scholar
  82. Haase H, Hebel S, Engelhardt G et al (2006) Flow cytometric measurement of labile zinc in peripheral blood mononuclear cells. Anal Biochem 352:222–230PubMedCrossRefGoogle Scholar
  83. Habeebu SS, Liu J, Liu Y et al (2000) Metallothionein-null mice are more susceptible than wildtype mice to chronic CdCl(2)-induced bone injury. Toxicol Sci 56:211–219PubMedCrossRefGoogle Scholar
  84. Hainaut P, Mann K (2001) Zinc binding and redox control of p53 structure and function. Antioxid Redox Signal 3:611–623PubMedCrossRefGoogle Scholar
  85. Hall L, Williams K, Perry ACF et al (1998) The majority of human glutathione peroxidase type 5 (GPX5) transcripts are incorrectly spliced:implications for the role of GPX5 in the male reproductive tract. Biochem J 333:5–9PubMedGoogle Scholar
  86. Hernandez J, Carrasco J, Belloso E et al (2000) Metallothionein induction by restraint stress:role of glucocorticoids and IL-6. Cytokine 12:791–796PubMedCrossRefGoogle Scholar
  87. Hill CH (1976) Mineral interrelationships. In:Prasad AS (ed) Trace elements, human health and disease. Academic Press, New York, pp 281–300Google Scholar
  88. Ho E, Quan N, Tsai YH et al (2001) Dietary zinc supplementation inhibits NF-kappaB activation and protects against chemically induced diabetes in CD1 mice. Exp Biol Med 226:103–111Google Scholar
  89. Holmgren A (1985) Thioredoxin. Annu Rev Biochem 54:237–271PubMedCrossRefGoogle Scholar
  90. Hujanen ES, Seppa ST, Virtanen K (1995) Polymorphonuclear leukocyte chemotaxis induced by zinc, copper and nickel in vitro. Biochim Biophys Acta 1245:145–152PubMedGoogle Scholar
  91. Ibs KH, Rink L (2003) Zinc-altered immune function. J Nutr 133(5 Suppl 1):1452S–1456SPubMedGoogle Scholar
  92. Iwata T, Incefy GS, Tanaka T et al (1979) Circulating thymic hormone levels in zinc deficiency. Cell Immunol 47:100–105PubMedCrossRefGoogle Scholar
  93. Jacob C, Maret W, Vallee BL (1999) Selenium redox biochemistry of zinc-sulfur coordination sites in proteins and enzymes. Proc Natl Acad Sci U S A 96:1910–1914PubMedCrossRefGoogle Scholar
  94. Jacobs MM (1983) Selenium inhibition of 1,2-dimethylhydrazine-induced colon carcinogenesis. Cancer Res 43:1646–1649PubMedGoogle Scholar
  95. Johnson LJ, Meacham SL, Kruskall LJ (2003) The antioxidants—vitamin C, vitamin E, selenium, and carotenoids. J Agromedicine 9:65–82PubMedCrossRefGoogle Scholar
  96. Kagi JH, Schaffer A (1998) Biochemistry of metallothionein. Biochemistry 127:8509–8515Google Scholar
  97. Kahmann L, Uciechowski P, Warmuth S et al (2006) Effect of improved zinc status on T helper cell activation and TH1/TH2 ratio in healthy elderly individuals. Biogerontology 7:429–435PubMedCrossRefGoogle Scholar
  98. Kant AK (2000) Consumption of energy-dense, nutrient-poor foods by adult Americans:nutritional and health implications. The third National Health and Nutrition Examination Survey, 1988–1994. Am J Clin Nutr 72:929–936PubMedGoogle Scholar
  99. Kelly EJ, Quaife CJ, Froelick GJ et al (1996) Metallothionein I and II protect against zinc deficiency and zinc toxicity in mice. J Nutr 126:1782–1790PubMedGoogle Scholar
  100. Kim YH, Kim EY, Gwag BJ et al (1999) Zinc-induced cortical neuronal death with features of apoptosis and necrosis:mediation by free radicals. Neuroscience 89:175–182PubMedCrossRefGoogle Scholar
  101. Kiremidjian-Schumacher L, Roy M, Glickman R et al (2000) Selenium and immunocompetence in patients with head and neck cancer. Biol Trace Elem Res 73:97–111PubMedCrossRefGoogle Scholar
  102. Klotz LO, Kroncke KD, Buchczyk DP et al (2003) Role of copper, zinc, selenium and tellurium in the cellular defense against oxidative and nitrosative stress. J Nutr 133:1448S–1451SPubMedGoogle Scholar
  103. Kohrle J (2000) The deiodinase family:selenoenzymes regulating thyroid hormone availability and action. Cell Mol Life Sci 57:1853–1863PubMedCrossRefGoogle Scholar
  104. Kondo Y, Rusnak JM, Hoyt DG et al (1997) Enhanced apoptosis in metallothionein null cells. Mol Pharmacol 52:195–201PubMedGoogle Scholar
  105. Kryukov GV, Castellano S, Novoselov SV et al (2003) Characterization of mammalian selenoproteomes. Science 300:1439–1443PubMedCrossRefGoogle Scholar
  106. Lashley FR (2006) Emerging infectious diseases at the beginning of the 21st century. Online J Issues Nurs 11:2–6PubMedGoogle Scholar
  107. Lesourd B (2006) Nutritional factors and immunological ageing. Proc Nutr Soc 65:319–325PubMedCrossRefGoogle Scholar
  108. Levine RL, Mosoni L, Berlett BS et al (1996) Methionine residues as endogenous antioxidants in proteins. Proc Natl Acad Sci USA 93:15036–15040PubMedCrossRefGoogle Scholar
  109. Li GS, Wang F, Kang D et al (1985) Keshan disease:an endemic cardiomyopathy in China. Hum Pathol 16:602–609PubMedCrossRefGoogle Scholar
  110. Li H, Raman CS, Glaser CB et al (1999) Crystal structures of zinc-free and -bound heme domain of human inducible nitric-oxide synthase. Implications for dimer stability and comparison with endothelial nitric-oxide synthase. J Biol Chem 274:21276–21284PubMedCrossRefGoogle Scholar
  111. Li Y, Yang Y, Chen H (1995) Detection of enteroviral RNA in paraffin-embedded myocardial tissue from patients with Keshan by nested PCR. Zhonghua Yi Xue Za Zhi 75:344–345PubMedGoogle Scholar
  112. Licastro F, Chiricolo M, Mocchegiani E et al (1994) Oral zinc supplementation in Down’s syndrome subjects decreased infections and normalized some humoral and cellular immune parameters. J Intellect Disabil Res 38:149–162PubMedGoogle Scholar
  113. Liu JZ, Milner JA (1992) Age, dietary selenium and quantity of 7,12-dimethylbenz(a)anthracene influence the in vivo occurrence of rat mammary DNA adducts. J Nutr 122:1361–1368PubMedGoogle Scholar
  114. Liuzzi JP, Lichten LA, Rivera S et al (2005) Interleukin-6 regulates the zinc transporter Zip14 in liver and contributes to the hypozincemia of the acute-phase response. Proc Natl Acad Sci U S A 102:6843–6848PubMedCrossRefGoogle Scholar
  115. Malavolta M, Costarelli L, Giacconi R et al (2006) Single and three-color flow cytometry assay for intracellular zinc ion availability in human lymphocytes with Zinpyr-1 and double immunofluorescence:relationship with metallothioneins. Cytometry A 69:1043–1053PubMedGoogle Scholar
  116. Mann JJ, Fraker PJ (2005) Zinc pyrithione induces apoptosis and increases expression of Bim. Apoptosis 10:369–379PubMedCrossRefGoogle Scholar
  117. Maret W, Vallee BL (1998) Thiolate ligands in metallothionein confer redox activity on zinc clusters. Proc Natl Acad Sci U S A 95:3478–3482PubMedCrossRefGoogle Scholar
  118. Maret W (2003) Cellular zinc and redox states converge in the metallothionein/thionein pair. J Nutr 133(Suppl 1):1460S–1462SPubMedGoogle Scholar
  119. McKenzie RC, Rafferty TS, Beckett GJ (1998) Selenium:an essential element for immune function. Immunol Today 19:342–345PubMedCrossRefGoogle Scholar
  120. McGarrity TJ, Peiffer LP (1993) Selenium and difluoromethylornithine additively inhibit DMH-induced distal colon tumor formation in rats fed a fiber-free diet. Carcinogenesis 14:2335–2340PubMedCrossRefGoogle Scholar
  121. McVoy MA, Adler SP (1989). Immunologic evidence for frequent age-related cytomegalovirus reactivation in seropositive immunocompetent individuals. J Infect Dis 160:1–10PubMedGoogle Scholar
  122. Mecocci P, Polidori MC, Troiano L et al. (2000) Plasma antioxidants and longevity:a study on healthy centenarians. Free Radic Biol Med 28:1243–1248PubMedCrossRefGoogle Scholar
  123. Meydani M (2001) Nutrition interventions in aging and age-associated disease. Ann NY Acad Sci 928:226–235PubMedCrossRefGoogle Scholar
  124. Mills CF (1989) Zinc in human biology. Springer, LondonGoogle Scholar
  125. Miyaji C, Watanabe H, Toma H et al (2000) Functional alteration of granulocytes, NK cells, and natural killer T cells in centenarians. Hum Immunol 61:908–916PubMedCrossRefGoogle Scholar
  126. Mocchegiani E, Costarelli L, Giacconi R et al (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 127:517–525PubMedCrossRefGoogle Scholar
  127. Mocchegiani E, Giacconi R, Cipriano C et al (2002a) MTmRNA gene expression, via IL-6 and glucocorticoids, as potential genetic marker of immunosenescence:lessons from very old mice and humans. Exp Gerontol 37:349–357CrossRefGoogle Scholar
  128. Mocchegiani E, Giacconi, R, Cipriano C et al (2002b) Metallothioneins (I+II) and thyroid-thymus axis efficiency in old mice:role of corticosterone and zinc supply. Mech Ageing Dev 123:675–694CrossRefGoogle Scholar
  129. Mocchegiani E, Giacconi R, Cipriano C et al (2004) The variation during the circadian cycle of liver CD1d-unrestricted NK1.1+TCRγδ+cells lead to successful ageing. Role of metallothionein/ IL-6/gp130/PARP-1 interplay in very old mice. Exp Gerontol 39:775–788PubMedCrossRefGoogle Scholar
  130. Mocchegiani E, Giacconi R, Cipriano C et al (2007) Zinc, metallothioneins and longevity. Effect of zinc supplementation:Zincage study. Ann N Y Acad Sci (in press)Google Scholar
  131. Mocchegiani E, Muzzioli M, Cipriano C et al (1998) Zinc, T-cell pathways, aging:role of metallothioneins. Mech Ageing Dev 106:183–204PubMedCrossRefGoogle Scholar
  132. Mocchegiani E, Muzzioli M, Giacconi R et al (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 124:459–468PubMedCrossRefGoogle Scholar
  133. Mocchegiani E, Muzzioli M, Giacconi R (2000a) Zinc and immunoresistance to infection in aging:new biological tools. Trends Pharmacol Sci 21:205–208CrossRefGoogle Scholar
  134. Mocchegiani E, Muzzioli M, Giacconi R (2000b) Zinc, metallothioneins, immune responses, survival and ageing. Biogerontology 1:133–143CrossRefGoogle Scholar
  135. Mocchegiani E, Santarelli L, Muzzioli M et al (1995) Reversibility of the thymic involution and of age-related peripheral immune dysfunctions by zinc supplementation in old mice. Int J Immunopharmacol 17:703–718PubMedCrossRefGoogle Scholar
  136. Moroni F, Di Paolo ML, Rigo A et al (2005) Interrelationship among neutrophil efficiency, inflammation, antioxidant activity and zinc pool in very old age. Biogerontology 6:271–281PubMedCrossRefGoogle Scholar
  137. Mott JD, Werb Z (2004) Regulation of matrix biology by matrix metalloproteinases. Curr Opin Cell Biol 16:558–564PubMedCrossRefGoogle Scholar
  138. Nagase H, Woessner JF Jr (1999) Matrix metalloproteinases. J Biol Chem 274:21491–21494PubMedCrossRefGoogle Scholar
  139. Nitzan YB, Sekler I, Hershfinkel M et al (2002) Postnatal regulation of ZnT-1 expression in the mouse brain. Brain Res Dev Brain Res 137:149–157PubMedCrossRefGoogle Scholar
  140. Nordberg J, Arner ES (2001) Reactive oxygen species, antioxidants, and the mammalian thioredoxin system. Free Radic Biol Med 31:1287–1312PubMedCrossRefGoogle Scholar
  141. Olivieri O, Girelli D, Stanzial AM et al (1996) Selenium, zinc, and thyroid hormones in healthy subjects:low T3/T4 ratio in the elderly is related to impaired selenium status. Biol Trace Elem Res 51:31–41PubMedCrossRefGoogle Scholar
  142. Ostan R, Alberti S, Bucci L et al (2006) Effect of zinc ions on apoptosis in PBMCs from healthy aged subjects. Biogerontology 7:437–447PubMedCrossRefGoogle Scholar
  143. Padmaja S, Squadrito GL, Lemercier JN et al (1996) Rapid oxidation of DL-selenomethionine by peroxynitrite. Free Radic Biol Med 21:317–322PubMedCrossRefGoogle Scholar
  144. Paolisso G, Barbieri M, Bonafè M et al (2000) Metabolic age modelling:the lesson from centenarians. Eur J Clin Invest 10:888–894CrossRefGoogle Scholar
  145. Paramanantham R, Bay BH, Sit KH (1996) Flow cytometric evaluation of the DNA profile and cell cycle of zinc supplemented human Chang liver cells. Acta Paediatr Jpn 38:334–338PubMedGoogle Scholar
  146. Pawelec G, Akbar A, Caruso C et al (2005) Human immunosenescence:is it infectious? Immunol Rev 205:257–268PubMedCrossRefGoogle Scholar
  147. Pence BC, Buddingh F (1985) Effect of dietary selenium deficiency on incidence and size of 1,2- dimethylhydrazine-induced colon tumours in rats. J Nutr. 115:1196–1202PubMedGoogle Scholar
  148. Peretz A, Neve J, Desmedt J et al (1991) Lymphocyte response is enhanced by supplementation of elderly subjects with selenium-enriched yeast. Am J Clin Nutr 53:1323–1328PubMedGoogle Scholar
  149. Piantanelli L, Fabris N (1978) Hypopituitary dwarf and athymic nude mice and the study of the relationships among thymus, hormones, and aging. Birth Defects 14:315–333PubMedGoogle Scholar
  150. Prasad AS (1993a) Biochemistry of zinc. Plenum Press, New YorkGoogle Scholar
  151. Prasad AS (2000) Effects of zinc deficiency on Th1 and Th2 cytokine shifts. J Infect Dis 182:S62–S68PubMedCrossRefGoogle Scholar
  152. Prasad AS, Fitzgerald JT, Hess JW et al (1993b) Zinc deficiency in elderly patients. Nutrition 9, 218–224Google Scholar
  153. Provinciali M, Di Stefano G, Stronati S (1998) Flow cytometric analysis of CD3/TCR complex, zinc, and glucocorticoid-mediated regulation of apoptosis and cell cycle distribution in thymocytes from old mice. Cytometry 32:1–8PubMedCrossRefGoogle Scholar
  154. Rayman MP (2000) The importance of selenium to human health. Lancet 356:233–241PubMedCrossRefGoogle Scholar
  155. Range N, Changalucha J, Krarup H et al (2006) The effect of multi-vitamin/mineral supplementation on mortality during treatment of pulmonary tuberculosis:a randomised two-by-two factorial trial in Mwanza, Tanzania. Br J Nutr 95:762–770PubMedCrossRefGoogle Scholar
  156. Reid ME, Duffield-Lillico AJ, Garland L et al (2002) Selenium supplementation and lung cancer incidence:an update of the nutritional prevention of cancer trial. Cancer Epidemiol Biomarkers Prev 11:1285–1291PubMedGoogle Scholar
  157. Reynolds MG, Anh BH, Thu VH et al (2003) Factors associated with nosocomial SARS-CoV transmission among healthcare workers in Hanoi, Vietnam 2003. BMC Public Health 6:207–210CrossRefGoogle Scholar
  158. Rink L, Gabriel P (2000) Zinc and the immune system. Proc Nutr Soc 59:541–552PubMedCrossRefGoogle Scholar
  159. Rink L, Haase H (2007) Zinc homeostasis and immunity. Trends Immunol 28:1–4PubMedCrossRefGoogle Scholar
  160. Roussel AM, Kerkeni A, Zouari N et al (2003) Antioxidant effects of zinc supplementation in Tunisians with type 2 diabetes mellitus. J Am Coll Nutr 22:316–321PubMedGoogle Scholar
  161. Roy M, Kiremidjian-Schumacher L, Wishe HI et al (1995) Supplementation with selenium restores age-related decline in immune cell function. Proc Soc Exp Biol Med 209:369–375PubMedGoogle Scholar
  162. Rundlof AK, Arner ES (2004) Regulation of the mammalian selenoprotein thioredoxin reductase 1 in relation to cellular phenotype, growth, and signaling events. Antioxid Redox Signal 6:41–52PubMedCrossRefGoogle Scholar
  163. Sandstead HH (1995) Requirements and toxicity of essential trace elements, illustrated by zinc and copper. Am J Clin Nutr 61:621S–624SPubMedGoogle Scholar
  164. Sandstead HH, Henriksen LK, Greger JL et al (1982) Zinc nutriture in the elderly in relation to taste acuity, immune response, and wound healing. Am J Clin Nutr 36:1046–1059PubMedGoogle Scholar
  165. Sato M, Kondoh M (2002) Recent studies on metallothionein:protection against toxicity of heavy metals and oxygen free radicals. Tohoku J Exp Med 196:9–22PubMedCrossRefGoogle Scholar
  166. Satoh M, Nishimura N, Kanayama Y et al (1997) Enhanced renal toxicity by inorganic mercury in metallothionein-null mice. J Pharmacol Exp Ther 283:1529–1533PubMedGoogle Scholar
  167. Savarino L, Granchi D, Ciapetti G et al (2001) Serum concentrations of zinc and selenium in elderly people:results in healthy nonagenarians/centenarians. Exp Gerontol 36:327–339PubMedCrossRefGoogle Scholar
  168. Schwarz S (1976) Essentiality and metabolic functions of selenium. Med Clin North Am 60:745–758PubMedGoogle Scholar
  169. Seiler WO (2001) Clinical pictures of malnutrition in ill elderly subjects. Nutrition 17:496–498PubMedCrossRefGoogle Scholar
  170. Semba RD, Bartali B, Zhou J et al (2006) Low serum micronutrient concentrations predict frailty among older women living in the community. J Gerontol A Biol Sci Med Sci 61:594–599PubMedGoogle Scholar
  171. Shapiro SD (1998) Matrix metalloproteinase degradation of extracellular matrix:biological consequences. Curr Opin Cell Biol 10:602–608PubMedCrossRefGoogle Scholar
  172. Shenkin A (2006) Micronutrients in health and disease. Postgrad Med J 82:559–567PubMedCrossRefGoogle Scholar
  173. Shenoy KT, Lena KB, Sali N et al (2006) Rationale and design for the CARDIOVIT Study (Cardiovit, Atherosclerotic vascular disease and hyperhomocysteinemia:an epidemiological study in Indians, additionally evaluating the effect of Oral VITamin supplementation). Curr Med Res Opin 22:641–648PubMedCrossRefGoogle Scholar
  174. Stowe RP, Kozlova EV, Yetman DL et al (2007) Chronic herpesvirus reactivation occurs in aging. Exp Gerontol 42:563–570PubMedCrossRefGoogle Scholar
  175. Taylor GA, Blackshear PJ (1995) Zinc inhibits turnover of labile mRNAs in intact cells. J Cell Physiol 162:378–387PubMedCrossRefGoogle Scholar
  176. Thiesen HJ, Bach C (1991) Transition metals modulate DNA-protein interactions of SP1 zinc finger domains with its cognate target site. Biochem Biophys Res Commun 176:551–557PubMedCrossRefGoogle Scholar
  177. Thomson CD (2004) Assessment of requirements for selenium and adequacy of selenium status:a review. Eur J Clin Nutr 58:391–402PubMedCrossRefGoogle Scholar
  178. Turner RJ, Finch JM (1991) Selenium and the immune response. Proc Nutr Soc 50:275–285PubMedCrossRefGoogle Scholar
  179. Turnlund JR, Durkin N, Costa F et al (1986) Stable isotope studies of zinc absorption and retention in young and elderly men. J Nutr 116:1239–1247PubMedGoogle Scholar
  180. Vallee BL, Falchuk KH (1993) The biochemical basis of zinc physiology. Physiol Rev 73:79–118PubMedGoogle Scholar
  181. 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 175:4697–4705Google Scholar
  182. Walter R, Roy J (1971) Selenomethionine, a potential catalytic antioxidant in biological systems. J Org Chem 36 2561–2563CrossRefGoogle Scholar
  183. Wapnir RA, Khani DE, Bayne MA et al (1983) Absorption of zinc by the rat ileum:effects of histidine and other low-molecular-weight ligands. J Nutr 113:1346–1354PubMedGoogle Scholar
  184. Wasowicz W, Gromadzinska J, Rydzynski K et al (2003) Selenium status of low-selenium area residents:Polish experience. Toxicol Lett 137:95–101PubMedCrossRefGoogle Scholar
  185. Watson WH, Yang X, Choi YE et al (2004) Thioredoxin and its role in toxicology. Toxicol Sci 78:3–14PubMedCrossRefGoogle Scholar
  186. Wei WQ, Abnet CC, Qiao YL et al (2004) Prospective study of serum selenium concentrations and esophageal and gastric cardia cancer, heart disease, stroke, and total death. Am J Clin Nutr 79:80–85PubMedGoogle Scholar
  187. Wen T, Fan X, Li M et al (2006) Changes of metallothionein 1 and 3 mRNA levels with age in brain of senescence-accelerated mice and the effects of acupuncture. Am J Chin Med 34:435–447PubMedCrossRefGoogle Scholar
  188. West AK, Stallings R, Hildebrand CE et al (1990) Human metallothionein genes:structure of the functional locus at 16q13. Genomics 8:513–518PubMedCrossRefGoogle Scholar
  189. Whitney AR, Diehn M, Popper SJ et al (2003) Individuality and variation in gene expression patterns in human blood. Proc Natl Acad Sci U S A 100:1896–1901PubMedCrossRefGoogle Scholar
  190. Williams PD, Day T (2003) Antagonistic pleiotropy, mortality source interactions, and the evolutionary theory of senescence. Evolution Int J Org Evol 57:1478–1488Google Scholar
  191. Wiseman DA, Wells SM, Wilham J et al (2006) Endothelial response to stress from exogenous zinc (Zn2+) resembles that of NO-mediated nitrosative stress, and is protected by MT-1 overexpression. Am J Physiol Cell Physiol 291:C555–C568CrossRefGoogle Scholar
  192. Xia Y, Hill KE, Byrne DW, Xu J et al (2005) Effectiveness of selenium supplements in a low-selenium area of China. Am J Clin Nutr 81:829–834PubMedGoogle Scholar
  193. Yang X, Doser TA, Fang CX et al (2006) Metallothionein prolongs survival and antagonizes senescence-associated cardiomyocyte diastolic dysfunction:role of oxidative stress. FASEB J 20:1024–1026PubMedCrossRefGoogle Scholar
  194. Ye B, Maret W, Vallee BL (2001) Zinc metallothionein imported into liver mitochondria modulates respiration. Proc Natl Acad Sci 98:2317–2322PubMedCrossRefGoogle Scholar
  195. Yin X, Knecht DA, Lynes MA (2005) Metallothionein mediates leukocyte chemotaxis. BMC Immunol 6:21–31PubMedCrossRefGoogle Scholar
  196. Youn J, Lynes MA (1999) Metallothionein-induced suppression of cytotoxic T lymphocyte function:an important immunoregulatory control. Toxicol Sci 52:199–208PubMedCrossRefGoogle Scholar
  197. Yu CW, Chen JH, Lin LY (1997) Metal-induced metallothionein gene expression can be inactivated by protein kinase C inhibitor. FEBS Lett 420:69–73PubMedCrossRefGoogle Scholar
  198. Zangger K, Oz G, Haslinger E et al (2001) Nitric oxide selectively releases metals from the amino-terminal domain of metallothioneins:potential role at inflammatory sites. FASEB J 15:1303–1305PubMedGoogle Scholar
  199. Zincage project (2004–2007) www.zincage.org

Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • Eugenio Mocchegiani
    • 1
  • Marco Malavolta
    • 1
  1. 1.Immunology Ctr. section Nutrigenomic and Immunosenescence Res Dept. INRCAAnconaItaly

Personalised recommendations