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Biomedical subjects

Eugenio Mocchegiani

Publications and source records attributed to Eugenio Mocchegiani.

At least 19 recordsLinked to original sources
PubMed2006

CD14 C (-260)T polymorphism, atherosclerosis, elderly: role of cytokines and metallothioneins.

BACKGROUND: CD14 receptor is a mediator of the inflammatory response to bacterial products. A functional polymorphism in the promoter of the CD14 gene (CD14 C-260T) was associated with coronary heart disease and atherosclerosis albeit with conflicting data. METHODS: To better clarify the role of CD14 in atherosclerosis, we typed CD14 C-260T polymorphism in old Italian (Central of Italy) atherosclerotic patients with carotid stenosis related to lipid assessment, inflammation (soluble CD14, IL-6 serum levels) and IL-6, TNF-alpha, IL-10, Metallothioneins (MT) gene expressions in carotid plaques. RESULTS: There was an increased frequency of TT homozygotes in patients when compared to controls [26% vs. 13.5%, odds ratio=2.25 (95% C.I., 1.23-4.09, p=0.0082) (Fisher's Exact test)]. Subjects with TT genotype showed a significant increase of soluble CD14 and enhanced MT2A, IL-6, TNF-alpha and decreased IL-10 gene expressions within the carotid plaques. On the basis of lipid assessment, hypercholesterolemic -260TT CD14 patients displayed lower HDL cholesterol and higher triglyceride than did CT and CC carriers. Using Pearson's correlation, a high MT2A expression was associated with high IL-6, TNF-alpha, sCD14 and thereby with severe chronic inflammation. CONCLUSIONS: These data provide insight into the pathogenetic role of the CD14 C-260T polymorphism in atherosclerosis as -260TT genotype may favour increased inflammation in atheroma promoting possible worsening atherosclerosis, at least in Central of Italy elderly population. Further studies are in progress in cohorts from different European geographic area (Zincage project).

Aged↗
PubMed2006

Zinc-binding proteins (metallothionein and alpha-2 macroglobulin) and immunosenescence.

Zinc is a relevant trace element for the efficiency of the entire immune system. The binding of zinc with some proteins, such as metallothioneins (MT) and alpha-2 macroglobulin (alpha-2M) is crucial for the immune efficiency during ageing and in age-related diseases, because these proteins may be involved in antagonistic pleiotropic effects. Indeed, the presence of chronic inflammation during ageing, generally, induces overexpression of these proteins that, due to their original biological function in fighting stressor agents, continuously sequester intracellular zinc. As a consequence, a low zinc ion availability may appear in aged organisms leading to impairments of the immune response at thymic and extrathymic levels with the risk of the appearance of age-related diseases. Therefore, MT and alpha-2M turn from protective in "young-adult age" to harmful agents in "ageing" following the basic assumption of an evolutionary theory of ageing, named the "antagonistic pleiotropy", which suggests that a trade off between early beneficial effects and late negative outcomes can occur at a genetic and molecular level. On the other hand, some polymorphisms of MT (MT2A) and alpha-2M have been associated with atherosclerosis or Alzheimer disease, respectively. Physiological zinc supplementation in elderly restores the thymic endocrine activity and innate immune response (NK cell cytotoxicity) and increases the survival rate in old mice. Therefore, zinc supplementation is useful to achieve health longevity because these zinc-binding proteins may regain their original protective task against oxidative damage with, thus, a beneficial impact on immune response.

Adult↗
PubMed2006

Single and three-color flow cytometry assay for intracellular zinc ion availability in human lymphocytes with Zinpyr-1 and double immunofluorescence: relationship with metallothioneins.

BACKGROUND: : The amount of available intracellular zinc is pivotal to regulate many cellular processes, including oxidative stress response and apoptotic mechanisms. Therefore it is not surprising that zinc homeostasis and dyshomeostasis is involved in many physiological and pathological states, respectively. Cell permeable zinc probes allow intracellular applications with microscopy technology, but flow cytometry (FC) applications have been scarcely explored, albeit they can be suited to study zinc homeostasis in different cell types, including rare cells. METHODS: : We describe a FC method able to estimate intracellular zinc ion availability and the intracellular capability to activate a zinc signal after treatment with an NO-donor (AcOM-DEA/NO) in human PBMCs, using the fluorescent zinc-specific probe, Zinpyr-1 (ZP1), alone or in association with CD4-PE and CD8-Cychrome mAb. RESULTS: : This method was able to detect an increase/decrease of intracellular zinc available in human fresh cultured PBMC and in immune subsets using AcOM-DEA/NO or TPEN, respectively. ZP1 mean fluorescence on gated histograms was sensitive to the amount of zinc added in the culture medium and significantly correlated to metallothioneins and total intracellular zinc. CONCLUSIONS: : FC applications using ZP1 may be a fast and useful tool to study zinc homeostasis in immune cells.

Adult↗
PubMed2006

Plasticity of neuroendocrine-thymus interactions during ontogeny and ageing: role of zinc and arginine.

Thymic re-growth and reactivation of thymic functions may be achieved in old animals by different endocrinological or nutritional manipulations such as, (a) treatment with melatonin, (b) implantation of a growth hormone (GH) secreting tumour cell line (GH3 cells) or treatment with exogenous GH, (c) castration or treatment with exogenous luteinizing hormone-releasing hormone (LHRH), (d) treatment with exogenous thyroxin or triiodothyronine, and (e) nutritional interventions such as arginine or zinc supplementation. These data strongly suggest that thymic involution is a phenomenon secondary to age-related alterations in neuroendocrine-thymus interactions and that it is the disruption of these interactions in old age that is responsible for age-associated immune-neuroendocrine dysfunctions. The targets involved in hormones-induced thymic reconstitution may directly or indirectly involve hormone receptors, cytokines, arginine, and a trace element such as zinc, which is pivotal for the efficiency of neuroendocrine-immune network during the whole life of an organism. The effect of GH, thyroid hormones, and LHRH may be due to specific hormone receptors on thymocytes and on thymic epithelial cells (TECs), which synthesize thymic peptides. Melatonin may also act through specific receptors on T-cells. In this context, the role of zinc, which turnover is reduced in old age, is pivotal because of its involvement through zinc fingers in the gene expression of hormone receptors. In addition, the effects of zinc are multifaceted: from the reactivation of zinc-dependent enzymes, to cell proliferation and apoptosis, to cytokines expression and to the reactivation of thymulin, which is a zinc-dependent thymic hormone required for intrathymic T-cell differentiation and maturation as well as for the homing of stem cells into the thymus. Zinc is also required for arginine action, via NO pathway. The role of zinc is therefore crucial in neuroendocrine-thymus interactions. According to data in animals and humans, the above reported endocrinological manipulations (GH, thyroid hormones, and melatonin) or arginine treatment may also act via zinc pool in restoring thymic activity in ageing allowing improvements on peripheral immune efficiency.

Aging↗
PubMed2006

Zinc, oxidative stress, genetic background and immunosenescence: implications for healthy ageing.

The relevance of zinc for proper functioning of the entire immune system is already well documented. However, the identification of individuals who really need zinc supplementation is still debated in view of the fact that excessive zinc may also be toxic. The risk of developing zinc deficiency in people from industrialized countries is relatively low, except for elderly subjects where zinc intake may be suboptimal and inflammation is chronic. Thus, the role of zinc on the immune system and on the health of European elderly people is becoming of paramount importance, considering also that the elderly population is rapidly increasing. In particular, the factors contributing to and the biochemical markers of zinc deficiency in the elderly are still remain to be established. Epidemiological, functional, and genetic studies aimed at formulating a rationale for the promotion of healthy ageing through zinc supplementation was the subject of an International Conference held in Madrid from 11-13 February 2006 (3rd ZincAge Meeting) at the CNIO Institute (local organizer: Maria Blasco, partner of ZincAge).

Journal Article↗
PubMed2006

Synaptic and mitochondrial physiopathologic changes in the aging nervous system and the role of zinc ion homeostasis.

Brain performances, e.g. learning and memory, decay during aging. Deterioration of synaptic junctions, as structural correlates of these key functions of the central nervous system, may play a central role in this impairment. Current research on the age-related changes of synapses is documenting that the numeric loss of contacts appears to trigger a compensatory reaction by the old CNS, i.e. the surviving junctional areas in old individuals are larger than in adult subjects. The final outcome of the balanced changes in synaptic number and size is that the overall synaptic junctional area per cubic micron of neuropil is also reduced in aging and this may account for the age-associated functional decay of CNS performances. Among the suggested determinants of synaptic deterioration in aging, a considerable number of recent studies support an early and pivotal role of the progressive decline of the mitochondrial metabolic competence, i.e. the capacity of select pools of organelles to provide adequate amounts of adenosine triphosphate. Quantitative ultrastructural studies together with cytochemistry of key enzymes of the respiratory chain (cytochrome oxidase and succinic dehydrogenase) have shown that mitochondrial dysfunctions play an early and central role in synaptic deterioration events associated with aging and neurodegenerative diseases. Among the various causes, the multiple mechanisms and molecules involved in zinc ion homeostasis have been supposed to be less efficient in the aging brain. Thus, a transient imbalance of free zinc ion concentration in the cytosol ([Zn2+]i) can be considered an unfavourable trigger of subtle mitochondrial damage and synaptic pathology.

Aged↗
PubMed2006

Genetic polymorphisms of inflammatory cytokines and myocardial infarction in the elderly.

Cardiovascular diseases (CVD), such as myocardial infarction (MI), are major causes of disability and mortality in the elderly. The increasing burden of CVD in ageing industrialized populations requires intensive research in order to improve preventive and therapeutic strategies especially in old people and if possible slow the processes of cardiovascular disease generation and progression. Ageing is accompanied by an age-dependent up-regulation of the inflammatory response, due to chronic antigenic stress stimulation, which potentially triggers the onset of inflammatory diseases, especially CVD. However, the exact mechanisms are still poorly understood. Since CVD are caused by interactions between genetic and environmental factors, a possible approach to their prevention is to identify the potential genetic component of inflammatory cardiovascular risk factors, providing the basis for personalized lifestyle modification and improved pharmacological therapy. Some common gene polymorphisms associated with high production of inflammatory molecules have been associated with atherosclerosis. Therefore, controlling inflammation might play a protective role against CVD, especially in ageing. Although a large number of studies of pro- and anti-inflammatory gene variants in association with CVD and MI exists, the emerging data are quite conflicting and do not provide definitive evidence for a role of these polymorphisms in the pathogenesis of MI. In this paper we review the evidence for a possible role of genetic polymorphisms of the most important inflammatory cytokines (IL-6, TNF-alpha, IL-10) and immune receptors (CD14 receptor and TLR-4) in modulating the incidence or the prognosis of MI, with a special focus in ageing population.

Aged↗
PubMed2006

Nutrient-gene interaction in ageing and successful ageing. A single nutrient (zinc) and some target genes related to inflammatory/immune response.

In this paper, we reviewed data regarding to the pivotal role played by the zinc-gene interaction in affecting some relevant cytokines (IL-6 and TNF-alpha) and heat shock proteins (Hsp70-2) in ageing, successful ageing (nonagenarians) and in some age-related diseases (atherosclerosis and infections). The polymorphisms of the genes codifying these proteins are predictive on one hand in longevity, such as IL-6 -174G/C locus, on the other hand 1267 Hsp70-2A/B or TNF-alpha -308G/A polymorphisms are associated to worsening atherosclerosis or severe infections, respectively, rather than longevity. Taking into account that longevity has a strong genetic component but, at the same time, is affected by life style and environmental factors, the analysis of these polymorphisms in association to some immune parameters (NK cell cytotoxicity) and nutritional factors (zinc) is a useful tool to unravel the role played by these genetic factors in longevity and in the appearance of age-related diseases. Indeed, these polymorphisms are associated with chronic inflammation, low zinc ion bioavailability, depressed innate immune response and high gene expression of metallothioneins, which have a limited zinc release for an optimal innate immune response in ageing. Therefore, the nutrient (zinc)-gene (IL-6, TNF-alpha and Hsp70-2) interaction is pivotal to keep under control the inflammatory/immune response with subsequent longevity, indicating these genes as "robust" for "healthy ageing".

Aged↗
PubMed2006

Psychosocial aspects and zinc status: is there a relationship with successful aging?

It is very interesting and innovative to study the interrelationships between biological characteristics, particularly zinc status, and psychosocial conditions in old age, because there are few and fragmentary data in the literature. The aim of this study was to examine the interrelationship between serum albumin value (an indicator of zinc status) and some psychosocial characteristics in elderly Italian volunteers recruited for the ZINCAGE project, which is supported by the European Commission in the Sixth Framework Programme (Food-CT-2003- 506850). A protocol of tests and questionnaires was used: the Lifestyle Questionnaire, the Mini-Mental Status Examination (MMSE), the Geriatric Depression Scale (GDS, 15 items), and the Perceived Stress Scale. A sample of 174 old subjects were recruited in Region Marche (Central Italy), and classified into three age groups: 65 to 74 years old, 75 to 84 years old, and >85 years old (including some nonagenarians). The preliminary results show that 69.7% of the subjects have no cognitive impairment; 66.5% have a value of the GDS scale indicating no depression; and 17% have an albumin deficiency. The majority of these are >85 years old and women. A relationship between level of albumin (used as indicator of zinc status) and depression has been found: 71% of subjects with albumin deficiency displayed a higher value on the depression test against 29% of subjects with a normal value (p < 0.01). These preliminary results show a relationship between serum albumin and psychological characteristics, in particular depression in an old Italian population. This further suggests that a zinc deficiency, via hypoalbumin values, is involved in impaired psychological characteristics in the elderly.

Aged↗
PubMed2006

Zinc homeostasis in aging: two elusive faces of the same "metal".

Proteins involved in zinc homeostasis may be altered in aging. This phenomenon may lead to zinc deficiency in the peripheral blood and an accumulation of zinc bound to insoluble aggregates at the extracellular level in the brain. Therefore, it should be more correct to talk about aging as a condition associated with zinc dyshomeostasis rather than deficiency. Restoring functional zinc homeostasis in aging people is an attractive field for antiaging research, but requires further knowledge than the current state of the art.

Aging↗
PubMed2006

Frequency of polymorphisms of signal peptide of TGF-beta1 and -1082G/A SNP at the promoter region of Il-10 gene in patients with carotid stenosis.

The role of inflammation in atherosclerosis is well recognized. We have evaluated the allele frequencies of the +869T/C and +915G/C polymorphisms (SNPs) at the TGF-beta1 gene and -1082G/A SNP at IL-10 promoter sequence, two well-known immunosuppressive and anti-inflammatory cytokines, in patients with carotid stenosis. Our data suggest a lack of association between these SNPs and the susceptibility to atherosclerosis although other reports have demonstrated this association. These results may be due to the pleiotropic effects of the cytokines and/or differences in haplotype combination that should be investigated to elucidate the role of TGF-beta1 and IL-10 polymorphisms in atherosclerosis.

Aged↗
PubMed2005

In vitro and in vivo effects of mercuric chloride on thymic endocrine activity, NK and NKT cell cytotoxicity, cytokine profiles (IL-2, IFN-gamma, IL-6): role of the nitric oxide-L-arginine pathway.

Mercury (Hg2+) affects cell-mediated immunity, including thymulin production. Thymulin, a zinc-dependent thymic hormone synthesized by thymic epithelial cells (TECs), is involved in NK cell cytotoxicity and Th1 cytokine production (IL-2 and IFN-gamma), which in turn affect both NKT and classic NK spleen cell cytotoxicity. High doses of Hg2+ induce an inflammatory status, increased production of IL-6 and consequent Th1/Th2 imbalance as well as cell-mediated immune depression. The mechanisms by which Hg+ affects the cell-mediated immune response are still unclear. The nitric oxide (NO) pathway may be implicated. The aim of this work was to further explore its noxious role in innate and adaptive immunity and to study the possible role played by the NO pathway. Young Balb/c mice treated in vivo for 1 month with 1.0 mg HgCl2/kg b.w. showed low thymulin activity, depressed NO production (as measured by nitrite and nitrate plasma levels), impaired classic NK spleen cell cytotoxicity, decreased Th1 (IL-2 and IFN-gamma) cytokine profiles, and increased IL-6 production. In vitro, 10(-6) M of HgCl2 inhibited active thymulin kinetics, TEC proliferation, NKT cell cytotoxicity and Th1 cytokine production, whereas IL-6 increased. L-arginine restored thymulin activity, TEC proliferation, NKT cytotoxicity, cytokine profiles and nitrite and nitrate plasma levels both in vivo and in vitro. Since L-arginine is the substrate for NO production, it may compensate for the cell-mediated immune defect induced by HgCl2, via the arginine-NO-pathway. L-arginine is also able to reduce glomerular kidney IgG antibodies deposits induced by higher dose of HgCl2 administration.

Animals↗
PubMed2005

Peripheral T lymphocyte changes in neonatal piglets: Relationship with growth hormone (GH), prolactin (PRL) and cortisol changes.

Taking into account the role played by the neuroendocrine network in affecting the early development of the immune response, the present study aims to assess neonatal immunity in piglets by testing peripheral lymphocyte age-related changes in relationship to plasma levels of some relevant immunoregulatory hormones, such as growth hormone (GH), prolactin (PRL) and cortisol. For this purpose, we studied the peripheral lymphocyte age-related changes in relationship to plasma levels of GH, PRL and cortisol in conventional piglets from birth (day 0) to 41 days of age. A significant decrease was observed in the total number of lymphocytes at day 0, with a subsequent constant increment up to 41 days of age. Concomitantly, the number of T cell subsets (mainly CD8(+) cells and double positive CD4(+)CD8(+)) was low at birth, with strong increments between the 19th and 41st days of life. The CD4(+) T cell number subset was less diminished at birth than that of CD8(+), albeit with significant increments in the post-weaning period. Of interest, gammadelta T cells, which are more involved in innate immune efficiency, displayed the same trend as CD8(+) T cells from birth to the 41st day of life. From day 0 up to the 19th day, significant inverse correlations were found between T cell subsets and GH or PRL or cortisol, albeit with more significant inverse correlations with cortisol. The high levels of GH and PRL in the pre-weaning period may be due to the fact that they have to counteract the cortisol-mediated negative effect on lymphocyte production and development. These findings suggest that stress condition occurs at birth with decreases in the immune parameters, in the same way as in human newborns, with a subsequent gradual normalisation and immune development, as shown by decreased cortisol, GH and PRL normalisation and concomitant increments in T cell subsets.

Age Factors↗
PubMed2005

1267 HSP70-2 polymorphism as a risk factor for carotid plaque rupture and cerebral ischaemia in old type 2 diabetes-atherosclerotic patients.

Patients with type 2 diabetes mellitus (NIDDM) are at risk for macrovascular disease complications, such as myocardial infarction (MI) or stroke from plaque rupture. Cytokines play a key role in plaque vulnerability. IFN-gamma inhibits collagen synthesis thereby affecting plaque stability. High IL-6, TNF-alpha, and dyslipidemia are risk factors for thrombosis. Abnormal increments of HSP70 in atherosclerotic plaques might lead to plaque instability and rupture caused by chronic inflammation, which up-regulates the expression of pro-inflammatory cytokines (IL-6 and TNF-alpha) in human monocytes. Studies of a polymorphic PstI site lying in the coding region at position 1267 of the HSP70-2 gene have shown that the BB genotype is associated with NIDDM. We screened 60 old NIDDM patients with carotid stenosis and 107 old healthy controls for 1267 HSP70-2 polymorphism in order to establish if an association with plaque frailty exists. Different genotypic distributions were observed between patients and healthy controls. An increased relative risk was associated with the B allele (p = 0.0107; odds ratio = 1.861). HSP70-2, IL-6, IFN-gamma, TNF-alpha gene expressions within the plaques and serum levels of triglyceride, total cholesterol and LDL cholesterol were tested from patients stratified according to their B+ (AB and BB) and B- (AA) genotypes. Plaque morphology (soft or fibrous-calcified) and the incidence of cerebral ischaemia were also assessed. B+ patients showed increased HSP70-2, IL-6, IFN-gamma, TNF-alpha and dyslipidemia as compared to B- carriers. The frequency of soft plaques increased in B+ in comparison to B- patients (67% versus 13%; odds ratio 13.0, p = 0.0006). A higher frequency of cerebral ischaemia (ictus or transient ischaemic attack (TIA)) was present in B+ than in B- genotype (53% versus 20%; odds ratio 4.57, p < 0.05) Hence, 1267 HSP70-2 polymorphism may be of use in identifying B+ NIDDM patients at risk for carotid plaque rupture and cerebral ischaemia.

Aged↗
PubMed2005

Interrelationship among neutrophil efficiency, inflammation, antioxidant activity and zinc pool in very old age.

Neutrophils are the first barrier against infections. Aged neutrophils display impaired oxidative burst and phagocytosis with subsequent less capability to destroy bacteria. In successful ageing (nonagenarians), neutrophil efficiency (phagocytosis) increases. After ingested microbes, aged neutrophils are less prone to undergo apoptosis favouring chronic inflammation. Moreover, the superoxide dismutase (SOD) activity, which is necessary in avoiding ROS produced by oxidative burst, is limited in ageing. The mechanisms of age-related changes in neutrophil function are not fully understood, taking also into account that nonagenarians escape infections in comparison with elderly. Zinc pool may be involved because it is pivotal for neutrophil efficiency and SOD activity. Since zinc also controls the inflammation, via IL-6 and soluble factor of gp130 (sgp130), we have assessed the possible interrelationship among oxidative burst, apoptosis, inflammation, SOD, adhesion molecule Mac-1 and zinc pool in elderly and in nonagenarians. The oxidative burst and the capacity to increase Mac-1 after PMA stimulation decrease both in elderly and nonagenarians, but the latter display a slight increased neutrophil induced apoptosis, decreased sgp130, increased SOD, and more neutrophil zinc content, as it occurs in young-adults. Significant correlation exists between sgp130 and zinc pool in very old age. These findings suggest lower chronic inflammation in nonagenarians, via more zinc available, with subsequent long-life survival. Therefore, a more correct interrelationship among neutrophil efficiency, inflammation, antioxidant activity and zinc pool exists in successful ageing with subsequent more effectiveness to control the inflammatory response to pathogens.

Adult↗
PubMed2005

Novel -209A/G MT2A polymorphism in old patients with type 2 diabetes and atherosclerosis: relationship with inflammation (IL-6) and zinc.

Vascular complications, including ischaemic cardiomyopathy, are the major causes of death in old diabetic patients. Chronic inflammation due to high IL-6 production occurs in type 2 diabetes (NIDDM) and atherosclerosis. High levels of IL-6 are associated with hyperglycaemia, dyslipidemia and provoke insulin resistance. In ageing and inflammation, IL-6 affects Metallothionein (MT) homeostasis, which in turn is involved in zinc turnover. Zinc deficiency is an usual event in ageing, inflammation, type 2 diabetes and atherosclerosis. No genetic study exists on MT polymorphisms in NIDDM-atherosclerotic patients. The aim of the present study is to screen a single nucleotide polymorphism in the promoter region of the MT2A gene in relation to inflammation (IL-6) and plasma zinc in NIDDM-atherosclerotic patients. The -209 A/G MT2A polymorphism is associated with chronic inflammation (higher plasma levels of IL-6), hyperglycaemia, enhanced HbA1c and more marked zinc deficiency in AA than AG genotype carrying patients. Analysing patients and controls subdivided in AA and AG genotypes, significant interactions existed between disease status and genotypes for glucose and zinc. AA patients are more at risk of developing NIDDM in association with atherosclerosis (p=0.0015 odds ratio=2.617) and its complications, such as ischaemic cardiomyopathy (p=0.0050 odds ratio=12.6). In conclusion, high levels of IL-6 unmask the phenotypes (higher insulin resistance and zinc deficiency) in relation to the genotypes with subsequent risk of developing ischaemic cardiomyopathy in NIDDM-atherosclerotic patients carrying AA genotype. Hence, the novel -209A/G MT2A polymorphism may be a further useful tool for the prevention, diagnosis and therapy of these combined pathologies in the elderly.

Aged↗
PubMed2005

Brain, aging and neurodegeneration: role of zinc ion availability.

Actual fields of research in neurobiology are not only aimed at understanding the different aspects of brain aging but also at developing strategies useful to preserve brain compensatory capacity and to prevent the onset of neurodegenerative diseases. Consistent with this trend much attention has been addressed to zinc metabolism. In fact, zinc acts as a neuromodulator at excitatory synapses and has a considerable role in the stress response and in the functionality of zinc-dependent enzymes contributing to maintaining brain compensatory capacity. In particular, the mechanisms that modulate the free zinc pool are pivotal for safeguarding brain health and performance. Alterations in zinc homeostasis have been reported in Parkinson's and Alzheimer's disease as well as in transient forebrain ischemia, seizures and traumatic brain injury, but little is known regarding aged brain. There is much evidence that that age-related changes, frequently associated to a decline in brain functions and impaired cognitive performances, could be related to dysfunctions affecting the intracellular zinc ion availability. A general agreement emerges from studies of humans' and rodents' old brains about an increased expression of metallothionein (MT) isoforms I and II, but dyshomogenous results are reported for MT-III, and it is still uncertain whether these proteins maintain in aging the protective role, as it occurs in adult/young age. At the same time, there is considerable evidence that amyloid-beta deposition in Alzheimer's disease is induced by zinc, but the pathological significance and the causes of this phenomenon are still an open question. The scientific debate on the role of zinc and of some zinc-binding proteins in aging and neurodegenerative disorders, as well as on the beneficial effect of zinc supplementation in aged brain and neurodegeneration, is extensively discussed in this review.

Aging↗