Zinc, T-cell pathways, aging: role of metallothioneins

Mocchegiani, Eugenio; Muzzioli, Mario; Cipriano, Catia; Giacconi, Robertina

doi:10.1016/s0047-6374(98)00115-8

Cited by 88 publications

(99 citation statements)

References 87 publications

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“…Zinc is a relevant trace element in the body. 27 Zn is present in large quantities throughout the mammalian brain, and the cheatable fraction of Zn is especially enriched in the neuropil of the neocortex and hippocampus. 28 Zn may have a special function in the brain concerning memory and learning.…”

Section: Resultsmentioning

confidence: 99%

Topographic Trace-Elemental Analysis in the Brain of Wistar Rats by X-ray Microfluorescence with Synchrotron Radiation

et al. 2008

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Knowledge about the spatial distribution and the local concentration of trace elements in tissues is of great importance, since trace elements are involved in many biological functions of living organisms. However, there are few methods available to measure the spatial (two (three)-dimensional) elemental distribution in animal brain. X-ray microfluorescence with synchrotron radiation is a multielemental mapping technique, which was used in this work to determine the topographic of iron, zinc and copper in coronal sections of female Wistar rats of different ages. Young (14 days old) and middle-aged (20 months old) rats (n = 8) were analyzed. The measurements were carried out at the XRF beam line at the Synchrotron Light National Laboratory (Campinas, Brazil). Two-dimensional scanning was performed in order to study the tendency of elemental concentration variation. The acquisition time for each pixel was 10 s/step and the step size was 300 mm/step in both directions. It was observed that the iron distribution was more conspicuous in the cortical area, thalamus and bellow the thalamus. On the other hand, the zinc distribution was more pronounced in the hippocampus. The iron, copper and zinc levels increased with advancing age. Therefore, this study reinforces the idea that these elements are involved in the chemical mechanisms of the brain that induce some neurological diseases, since they are also present in high levels in specific areas of the brain, such as the hippocampus and the substantia nigra of patients with these disorders.

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Section: Resultsmentioning

confidence: 99%

Topographic Trace-Elemental Analysis in the Brain of Wistar Rats by X-ray Microfluorescence with Synchrotron Radiation

et al. 2008

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“…The low intracellular zinc ion availability occurs despite the plasma zinc levels may be in the normal range, suggesting that the determination of plasma zinc can be misleading to detect a real zinc Mocchegiani et al (1998), Dardenne (2002), Bogden (2004), Haase et al (2006b), andPrasad (2008) Impairment of the immune response (cell-mediated immunity and humoral immunity) and impairment of thymic and extrathymic T cell pathways (NKT cell number and function) Eberle et al (1999) Abnormalities in bone growth and bone formation and mineralisation…”

Section: Dietary Zinc Deficienciesmentioning

confidence: 99%

“…Therefore, zinc supplementation may be of benefit in prevention or in reducing the risk or in delaying the appearance of diseases and the subsequent disability. For specific references see: Shankar andPrasad (1998), Fraker andTelford (1997), Mocchegiani et al (1998), Mocchegiani et al (2000), Prasad et al (2006), Prasad (2007), Haase and Rink (2009a, b), Bao et al (2010) and Prasad et al 2011) Evidences of the usefulness of zinc supplementation for immunity in the elderly began to emerge three decades ago with however inconsistent data on its beneficial effect upon the immune efficiency due to different doses and duration of zinc treatment as well as the form of zinc to be supplemented (Mocchegiani et al 2008d). Although zinc was used at the doses recommended by RDA (from 10 up to 40 mg/day) (U.S. Department of Agriculture 1996) improvements of both innate and adaptive immune responses are not so exciting and also contradictory.…”

Section: Potential Usefulness Of Zn Supplementation In Elderly Subjectsmentioning

confidence: 99%

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

Mocchegiani

Romeo

Malavolta

et al. 2012

AGE

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153

119

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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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“…Moreover, such allelic variants may be very useful tools in order to screen old subjects at risk for zinc deficiency on genetic basis, taking into account that the actual methodological procedures to test the ''zinc status'' are often misleading and that laboratory investigations to assay zinc ion bioavailability are scarcely reproducible and poorly applicable to clinical practice [65,103]. In this context, a novel reproducible system in testing intracellular zinc ion bioavailability has been developed using zinc fluorescent probe (Zynpir-1) associated with MT values, representing both tests valid methods to detect the intracellular zinc status [92].…”

Section: Zinc-mt Gene Interactionmentioning

confidence: 99%

Zinc–gene interaction related to inflammatory/immune response in ageing

Mocchegiani

Malavolta

2008

Genes Nutr

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The pivotal role played by zinc-gene interaction in affecting some relevant cytokines (IL-6 and TNF-a) and heat shock proteins (HSP70-2) in ageing, successful ageing (nonagenarians) and the most common age-related diseases, such as atherosclerosis and infections, is now recognized. The polymorphisms of genes codifying proteins related to the inflammation are predictive on one hand in longevity, on the other hand they are associated with atherosclerosis or severe infections. Since the health lifespan has a strong genetic component, which in turn also affected by nutritional factors like zinc, the association of these polymorphisms with innate immune response, zinc ion bioavailability and Metallothioneins (MT) homeostasis is an useful tool to unravel the role played by zinc-gene interactions in longevity, especially due to the inability of MT in zinc release in ageing and chronic inflammation. In ageing, this last fact leads to depressed innate immune response for host defence. In contrast, in very old age the inflammation is lower with subsequent more zinc ion bioavailability, less MT gene expression and satisfactory innate immunity. Therefore, the zinc-gene (IL-6, TNF-a, Hsp70-2) interactions, via MT homeostasis, are crucial to achieve successful ageing. Human genes and longevityAgeing is a universal phenomenon that affects nearly all of animal species. According to Helfand and Rogina [69], ageing can be characterized as: (1) an inevitable consequence of being a multicellular organism; (2) associated with a random, passive decline in function; (3) leading to a global loss of homeostasis over time and (4) mortality increasing with ageing. Evolutionary studies on ageing have drawn the attention on the importance of the genetic mechanisms involved in somatic maintenance and repair that secure longevity [82]. Evidence from model organisms has indicated that subtle variation in the genes can dramatically influence lifespan. However, findings on potential candidate genetic mechanisms determining ageing and lifespan in model organisms are far to explain variations in human populations because phenotypes are critically dependent on the setting in which genes are expressed, while laboratory conditions and modern environments are markedly dissimilar [86]. Genetic analysis of human ageing is mainly approached by searching the genetic basis of susceptibility to major geriatric disorders or the allelic contributions to exceptionally long life span. It is just thanks to these last studies in centenarians populations that several candidate longevity genes or pathways including PON1 [19,130], IGF1/insulin pathway [84,120], elements of lipid metabolism [12], stress response [34] and inflammatory response have been identified [53].Genes related to inflammation and stress response, in particular the pro-inflammatory cytokines IL-1, IL-6, TNFalpha, the anti-inflammatory cytokine IL-10, the HSP70 chaperones and the regulators of trace elements homeostasis, metallothioneins (MT), seem particularly relevant taking into accoun...

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Zinc, T-cell pathways, aging: role of metallothioneins

Cited by 88 publications

References 87 publications

Topographic Trace-Elemental Analysis in the Brain of Wistar Rats by X-ray Microfluorescence with Synchrotron Radiation

Topographic Trace-Elemental Analysis in the Brain of Wistar Rats by X-ray Microfluorescence with Synchrotron Radiation

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

Zinc–gene interaction related to inflammatory/immune response in ageing

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