Skip to main content

Advertisement

SpringerLink
Log in

Zinc, metallothioneins and immunosenescence: effect of zinc supply as nutrigenomic approach

  • Research Article
  • Published:
Biogerontology Aims and scope Submit manuscript

Abstract

Ageing is an inevitable biological process associated with gradual and spontaneous biochemical and physiological changes and increased susceptibility to diseases. Nutritional factor, zinc, known to be involved in improving immunity, may remodel some of the age-associated changes, leading to a healthy ageing. “In Vitro” studies involving human lymphocytes exposed to endotoxins, and “in vivo” studies comparing old and young mice fed with low dietary zinc suggest that zinc is important for both innate and adaptive immune efficiency, and more optimal inflammatory/immune response. The intracellular zinc homeostasis is mainly regulated by Metallothioneins (MT), via ion release through the reduction of thiol groups in MT molecule. These processes are crucial because mediating the zinc signalling within the immune cells assigning to zinc a role of “second messenger”. Zinc homeostasis is altered in ageing partly due to higher expression levels of MT, leading to an increased sequestration of zinc, resulting in less availability of free intracellular zinc. Improvement of immune functions and stress response systems occurs in elderly after physiological zinc supplementation. The main reason behind these effects seems to be related to a like “hormetic” response induced by zinc. However, the choice of old subjects for zinc supplementation has to be performed in relationship to the specific genetic background of MT and pro-inflammatory cytokine (IL-6) because the latter is involved both in MT gene expression and in intracellular zinc homeostasis. Old subjects carrying GG genotypes (termed C− carriers) in IL-6 −174G/C locus display increased IL-6 production, low intracellular zinc ion availability, impaired innate immune response and enhanced MT. By contrast, old subjects carrying GC and CC genotypes (termed C+ carriers) in the same IL-6 −174 locus displayed satisfactory intracellular zinc and innate immune response. Moreover, male carriers of C+ allele are more prone to reach centenarian age than C− ones. Therefore, old C− subjects are likely to benefit more from zinc supplementation restoring NK cell cytotoxicity and improving the zinc status. Plasma zinc deficiency and the altered immune response is more evident when the genetic variations of IL-6 polymorphism are associated with the genetic variations of MT1A in position +647, suggesting that the genetic variations of IL-6 and MT1A are very useful tools for the identification of old people who effectively need zinc supplementation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

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

    Article  PubMed  CAS  Google Scholar 

  • Ames BN (2006) Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage. Proc Natl Acad Sci USA 103:17589–17594

    Article  PubMed  CAS  Google Scholar 

  • Anantharaju A, Feller A, Chedid A (2002) Aging liver. Gerontology 48:343–353

    Article  PubMed  CAS  Google Scholar 

  • Bahadorani S, Mukai S, Egli D, Hilliker AJ (2010) Overexpression of metalresponsive transcription factor (MTF-1) in Drosophila melanogaster ameliorates life-span reductions associated with oxidative stress and metal toxicity. Neurobiol Aging 31:1215–1226

    Article  PubMed  CAS  Google Scholar 

  • 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 15:627–634

    Article  PubMed  CAS  Google Scholar 

  • Bauer JH, Helfand SL (2006) New tricks of an old molecule: lifespan regulation by p53. Aging Cell 5:437–440

    Article  PubMed  CAS  Google Scholar 

  • Bauer J, Ganter U, Abel J, Strauss S, Jonas U, Weiss R, Gebicke-Haerter P, Volk B, Berger M (1993) Effects of interleukin-1 and interleukin-6 on metallothionein and amyloid precursor protein expression in human neuroblastoma cells. Evidence that interleukin-6 possibly acts via a receptor different from the 80-kDa interleukin-6 receptor. J Neuroimmunol 45:163–173

    Article  PubMed  CAS  Google Scholar 

  • Bui LM, Dressendorfer RH, Keen CL, Summary JJ, Dubick MA (1994) Zinc status and interleukin-1 beta-induced alterations in mineral metabolism in rats. Proc Soc Exp Biol Med 206:438–444

    PubMed  CAS  Google Scholar 

  • Cai L, Satoh M, Tohyama C, Cherian MG (1999) Metallothionein in radiation exposure: its induction and protective role. Toxicology 132:85–98

    Article  PubMed  CAS  Google Scholar 

  • Chimienti F, Seve M, Richard S, Mathieu J, Favier A (2001) Role of cellular zinc in programmed cell death: temporal relationship between zinc depletion, activation of caspases, and cleavage of Sp family transcription factors. Biochem Pharmacol 62:51–62

    Article  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

    Article  PubMed  CAS  Google Scholar 

  • Cousins RJ, Liuzzi JP, Lichten LA (2006) Mammalian zinc transport, trafficking, and signals. J Biol Chem 281:24085–24089

    Article  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

    Article  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 

  • Ebadi M, Swanson S (1988) The status of zinc, copper, and metallothionein in cancer patients. Prog Clin Biol Res 259:161–175

    PubMed  CAS  Google Scholar 

  • Failla ML (2003) Trace elements and host defence: recent advances and continuing challenges. J Nutr 133(Suppl. 1):1443S–1447S

    PubMed  CAS  Google Scholar 

  • Feng W, Cai J, Pierce WM, Franklin RB, Maret W, Benz FW, Kang YJ (2005) Metallothionein transfers zinc to mitochondrial aconitase through a direct interaction in mouse hearts. Biochem Biophys Res Commun 332:853–858

    Article  PubMed  CAS  Google Scholar 

  • Feng W, Benz FW, Cai J, Pierce WM, Kang YJ (2006) Metallothionein disulfides are present in metallothionein-overexpressing transgenic mouse heart and increase under conditions of oxidative stress. J Biol Chem 281:681–687

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Goode HF, Kelleher J, Walker BE (1989) Zinc concentrations in pure populations of peripheral blood neutrophils, lymphocytes and monocytes. Ann Clin Biochem 26:85–95

    Google Scholar 

  • Haase H, Rink L (2009) The immune system and the impact of zinc during aging. Immun Ageing 6:9–17

    Article  PubMed  Google Scholar 

  • Habeebu SS, Liu J, Liu Y, Klaassen CD (2000) Metallothionein-null mice are more susceptible than wild-type mice to chronic CdCl(2)-induced bone injury. Toxicol Sci 56:211–219

    Article  PubMed  CAS  Google Scholar 

  • Hernández J, Molinero A, Campbell IL, Hidalgo J (1997) Transgenic expression of interleukin 6 in the central nervous system regulates brain metallothionein-I and -III expression in mice. Brain Res Mol Brain Res 48:125–131

    Article  PubMed  Google Scholar 

  • Hujanen ES, Seppa ST, Virtanen K (1995) Polymorphonuclear leukocyte chemotaxis induced by zinc, copper and nickel in vitro. Biochim Biophys Acta 1245:145–152

    PubMed  Google Scholar 

  • Ibs KH, Rink L (2003) Zinc-altered immune function. J Nutr 133(Suppl 1):1452S–1456S

    PubMed  CAS  Google Scholar 

  • Iwata T, Incefy GS, Tanaka T, Fernandes G, Menendez-Botet CJ, Pih K, Good RA (1979) Circulating thymic hormone levels in zinc deficiency. Cell Immunol 47:100–105

    Article  PubMed  CAS  Google Scholar 

  • Kagi JH, Schaffer A (1998) Biochemistry of metallothionein. Biochemistry 127:8509–8515

    Google Scholar 

  • Kant AK (2000) Consumption of energy-dense, nutrient-poor foods by adult Americans: nutritional, health implications. The third National Health, Nutrition Examination Survey,1988–1994. Am J Clin Nutr 72:929–936

    PubMed  CAS  Google Scholar 

  • Kelly EJ, Quaife CJ, Froelick GJ, Palmiter RD (1996) Metallothionein I and II protect against zinc deficiency and zinc toxicity in mice. J Nutr 126:1782–1790

    PubMed  CAS  Google Scholar 

  • Kindermann B, Döring F, Fuchs D, Pfaffl MW, Daniel H (2005) Effects of increased cellular zinc levels on gene and protein expression in HT-29 cells. Biometals 18:243–253

    Article  PubMed  CAS  Google Scholar 

  • Kondo Y, Rusnak JM, Hoyt DG, Settineri CE, Pitt BR, Lazo JS (1997) Enhanced apoptosis in metallothionein null cells. Mol Pharmacol 52:195–201

    PubMed  CAS  Google Scholar 

  • Kroncke KD, Klotz LO, Suschek CV, Sies H (2002) Comparing nitrosative versus oxidative stress toward zinc finger-dependent transcription. Unique role for NO. J Biol Chem 277:13294–13301

    Article  PubMed  CAS  Google Scholar 

  • Kuppusamy UR, Dharmani M, Kanthimathi MS, Indran M (2005) Antioxidant enzyme activities of human peripheral blood mononuclear cells exposed to trace elements. Biol Trace Elem Res 106:29–40

    Article  PubMed  CAS  Google Scholar 

  • Lamore SD, Wondrak GT (2011) Zinc pyrithione impairs zinc homeostasis and upregulates stress response gene expression in reconstructed human epidermis. Biometals. doi:10.1007/s10534-011-9441-6

  • Lee WW, Cui D, Czesnikiewicz-Guzik M, Vencio RZ, Shmulevich I, Aderem A, Weyand CM, Goronzy JJ (2008) Age-dependent signature of metallothionein expression in primary CD4 T cell responses is due to sustained zinc signaling. Rejuvenation Res 11:1001–1011

    Article  PubMed  CAS  Google Scholar 

  • Lesourd B (2006) Nutritional factors and immunological ageing. Proc Nutr Soc 65:319–325

    Article  PubMed  CAS  Google Scholar 

  • Liu J, Atamna H, Kuratsune H, Ames BN (2002) Delaying brain mitochondrial decay and aging with mitochondrial antioxidants and metabolites. Ann NY Acad Sci 959:133–166

    Article  PubMed  CAS  Google Scholar 

  • Liuzzi JP, Cousins RJ (2004) Mammalian zinc transporters. Annu Rev Nutr 24:151–172

    Article  PubMed  CAS  Google Scholar 

  • Liuzzi JP, Lichten LA, Rivera S, Blanchard RK, Aydemir TB, Knutson MD, Ganz T, Cousins RJ (2005) Interleukin-6 regulates the zinc transporter Zip14 in liver and contributes to the hypozincemia of the acute-phase response. Proc Natl Acad Sci USA 102:6843–6848

    Article  PubMed  CAS  Google Scholar 

  • Magda D, Lecane P, Wang Z, Hu W, Thiemann P, Ma X, Dranchak PK, Wang X, Lynch V, Wei W, Csokai V, Hacia JG, Sessler JL (2008) Synthesis and anticancer properties of water-soluble zinc ionophores. Cancer Res 68:5318–5325

    Article  PubMed  CAS  Google Scholar 

  • Malavolta M, Costarelli L, Giacconi R, Muti E, Bernardini G, Tesei S, Cipriano C, Mocchegiani E (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 69:1043–1053

    PubMed  Google Scholar 

  • Malavolta M, Cipriano C, Costarelli L, Giacconi R, Tesei S, Muti E, Piacenza F, Pierpaoli S, Larbi A, Pawelec G, Dedoussis G, Herbein G, Monti D, Jajte J, Rink L, Mocchegiani E (2008) Metallothionein downregulation in very old age: a phenomenon associated with cellular senescence? Rejuvenation Res 11:455–459

    Article  PubMed  CAS  Google Scholar 

  • Mann JJ, Fraker PJ (2005) Zinc pyrithione induces apoptosis and increases expression of Bim. Apoptosis 10:369–379

    Article  PubMed  CAS  Google Scholar 

  • Maret W (2003) Cellular zinc and redox states converge in the metallothionein/thionein pair. J Nutr 133:S1460–S1462

    Google Scholar 

  • Maret W, Vallee BL (1998) Thiolate ligands in metallothionein confer redox activity on zinc clusters. Proc Natl Acad Sci USA 95:3478–3482

    Article  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

    Article  PubMed  CAS  Google Scholar 

  • Mattson MP (2008) Hormesis and disease resistance: activation of cellular stress response pathways. Hum Exp Toxicol 27:155–162

    Article  PubMed  Google Scholar 

  • Meydani M (2001) Nutrition interventions in aging and age-associated disease. Ann NY Acad Sci 928:226–235

    Article  PubMed  CAS  Google Scholar 

  • Mocchegiani E, Malavolta M (2008) Zinc-gene interaction related to inflammatory/immune response in ageing. Genes Nutr 3:61–75

    Article  PubMed  CAS  Google Scholar 

  • Mocchegiani E, Santarelli L, Muzzioli M, 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

    Article  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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Mocchegiani E, Muzzioli M, Giacconi R (2000b) Zinc, metallothioneins, immune responses, survival and ageing. Biogerontology 1:133–143

    Article  PubMed  CAS  Google Scholar 

  • Mocchegiani E, Giacconi R, Cipriano C, Gasparini N, Orlando F, Stecconi R, Muzzioli M, Isani G, Carpenè E (2002a) Metallothioneins (I+II) and thyroid-thymus axis efficiency in old mice: role of corticosterone and zinc supply. Mech Ageing Dev 123:675–694

    Article  PubMed  CAS  Google Scholar 

  • Mocchegiani E, Giacconi R, Cipriano C, Muzzioli M, Gasparini N, Moresi R, Stecconi R, Suzuki H, Cavalieri E, Mariani E (2002b) MTmRNA gene expression, via IL-6 and glucocorticoids, as potential genetic marker of immunosenescence: lessons from very old mice and humans. Exp Gerontol 37:349–357

    Article  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 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 39:775–788

    Article  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 (2007a) Zinc, metallothioneins, and longevity effect of zinc supplementation: zincage study. Ann NY Acad Sci 1119:129–146

    Article  PubMed  CAS  Google Scholar 

  • Mocchegiani E, Giacconi R, Muti E, Cipriano C, Costarelli L, Tesei S, Gasparini N, Malavolta M (2007b) Zinc-bound metallothioneins and immune plasticity: lessons from very old mice and humans. Immun Ageing 4:7–12

    Article  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 (2008) 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

    Article  PubMed  CAS  Google Scholar 

  • Mocchegiani E, Malavolta M, Costarelli L, Giacconi R, Cipriano C, Piacenza F, Tesei S, Basso A, Pierpaoli S, Lattanzio F (2010) Zinc, metallothioneins and immunosenescence. Proc Nutr Soc 69:290–299

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Ostan R, Alberti S, Bucci L, Salvioli S, Pasi S, Cevenini E, Capri M, Di Iorio A, Ginaldi L, De Martinis M, Franceschi C, Monti D (2006) Effect of zinc ions on apoptosis in PBMCs from healthy aged subjects. Biogerontology 7:437–447

    Article  PubMed  CAS  Google Scholar 

  • Paolisso G, Barbieri M, Bonafè M, Franceschi C (2000) Metabolic age modelling: the lesson from centenarians. Eur J Clin Invest 10:888–894

    Article  Google Scholar 

  • 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 32:1–8

    Article  PubMed  CAS  Google Scholar 

  • Putics A, Vödrös D, Malavolta M, Mocchegiani E, Csermely P, Soti C (2008) Zinc supplementation boosts the stress response in the elderly: Hsp70 status is linked to zinc availability in peripheral lymphocytes. Exp Gerontol 43:452–461

    Article  PubMed  CAS  Google Scholar 

  • Rattan SI, Demirovic D (2009) Hormesis can and does work in humans. Dose Response 8:58–63

    Article  PubMed  Google Scholar 

  • Rink L, Haase H (2007) Zinc homeostasis and immunity. Trends Immunol 28:1–4

    Article  PubMed  CAS  Google Scholar 

  • Sato M, Kondoh M (2002) Recent studies on metallothionein: protection against toxicity of heavy metals and oxygen free radicals. Tohoku J Exp Med 196:9–22

    Article  PubMed  CAS  Google Scholar 

  • Satoh M, Nishimura N, Kanayama Y, Naganuma A, Suzuki T, Tohyama C (1997) Enhanced renal toxicity by inorganic mercury in metallothionein-null mice. J Pharmacol Exp Ther 283:1529–1533

    PubMed  CAS  Google Scholar 

  • Schroeder JJ, Cousins RJ (1990) Interleukin 6 regulates metallothionein gene expression and zinc metabolism in hepatocyte monolayer cultures. Proc Natl Acad Sci USA 87:3137–3141

    Article  PubMed  CAS  Google Scholar 

  • Shenkin A (2006) Micronutrients in health and disease. Postgrad Med J 82:559–567

    Article  PubMed  CAS  Google Scholar 

  • Spahl DU, Berendji-Grun D, Suschek CV, Kolb-Bachofen V, Kröncke KD (2003) Regulation of zinc homeostasis by inducible NO synthase-derived NO: nuclear metallothionein translocation and intranuclear Zn2+ release. Proc Natl Acad Sci USA 100:13952–13957

    Article  PubMed  CAS  Google Scholar 

  • Swindell WR (2010) Metallothionein and the biology of aging. Ageing Res Rev 10:132–145

    Article  PubMed  Google Scholar 

  • Truong-Tran AQ, Carter J, Ruffin RE, Zalewski PD (2001) The role of zinc in caspase activation and apoptotic cell death. Biometals 14:315–330

    Article  PubMed  CAS  Google Scholar 

  • Tucker KL, Buranapin S (2001) Nutrition and aging in developing countries. J Nutr 9:2417S–2423S

    Google Scholar 

  • Turnlund JR, Durkin N, Costa F, Margen S (1986) Stable isotope studies of zinc absorption and retention in young and elderly men. J Nutr 116:1239–1247

    PubMed  CAS  Google Scholar 

  • Vallee BL, Falchuk KH (1993) The biochemical basis of zinc physiology. Physiol Rev 73:79–118

    Article  PubMed  CAS  Google Scholar 

  • West AK, Stallings R, Hildebrand CE, Chiu R, Karin M, Richards RI (1990) Human metallothionein genes: structure of the functional locus at 16q13. Genomics 8:513–518

    Article  PubMed  CAS  Google Scholar 

  • Williams PD, Day T (2003) Antagonistic pleiotropy, mortality source interactions, and the evolutionary theory of senescence. Evol Int J Org Evol 57:1478–1488

    Google Scholar 

  • Wong CP, Song Y, Elias VD, Magnusson KR, Ho E (2009) Zinc supplementation increases zinc status and thymopoiesis in aged mice. J Nutr 139:1393–1397

    Article  PubMed  CAS  Google Scholar 

  • Yang X, Doser TA, Fang CX, Nunn JM, Janardhanan R, Zhu M, Sreejayan N, Quinn MT, Ren J (2006) Metallothionein prolongs survival and antagonizes senescence associated cardiomyocyte diastolic dysfunction: role of oxidative stress. FASEB J 20:1024–1026

    Article  PubMed  CAS  Google Scholar 

  • Youn J, Lynes MA (1999) Metallothionein-induced suppression of cytotoxic T lymphocyte function: an important immunoregulatory control. Toxicol Sci 52:199–208

    Article  PubMed  CAS  Google Scholar 

  • Yu CW, Chen JH, Lin LY (1997) Metal-induced metallothionein gene expression can be inactivated by protein kinase C inhibitor. FEBS Lett 420:69–73

    Article  PubMed  CAS  Google Scholar 

  • Zangger K, Oz G, Haslinger E, Kunert O, Armitage IM (2001) Nitric oxide selectively releases metals from the amino-terminal domain of metallothioneins: potential role at inflammatory sites. FASEB J 15:1303–1305

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

Supported by INRCA, CARILORETO, CARIVERONA and European Project ZINCAGE: n. FOOD-CT-506850, Coordinator: Dr. Eugenio Mocchegiani.

Author information

Authors and Affiliations

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

    Eugenio Mocchegiani, Laura Costarelli, Robertina Giacconi, Francesco Piacenza, Andrea Basso & Marco Malavolta

Authors
  1. Eugenio Mocchegiani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Laura Costarelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Robertina Giacconi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Francesco Piacenza
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Andrea Basso
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Marco Malavolta
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Eugenio Mocchegiani.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mocchegiani, E., Costarelli, L., Giacconi, R. et al. Zinc, metallothioneins and immunosenescence: effect of zinc supply as nutrigenomic approach. Biogerontology 12, 455–465 (2011). https://doi.org/10.1007/s10522-011-9337-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10522-011-9337-4

Keywords

Search

Navigation