Main biomarkers associated with age-related plasma zinc decrease and copper/zinc ratio in healthy elderly from ZincAge study

Giacconi, Robertina; Costarelli, Laura; Piacenza, Francesco; Basso, Andrea; Rink, Lothar; Mariani, Erminia; Fülöp, Tamás; Dedoussis, George; Herbein, Georges; Provinciali, Mauro; Jajte, Jolanta; Lengyel, Imre; Mocchegiani, Eugenio; Malavolta, Marco

doi:10.1007/s00394-016-1281-2

Cited by 50 publications

(31 citation statements)

References 54 publications

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“…Elevated plasma or serum Cu to Zn ratio has been suggested to represent a marker of health status and a predictor of all-cause mortality in elderly population [40]. Consistent with the literature [22,40,42], we observed that Cu to Zn ratio significantly increased with aging. In the present work, elevated Fe concentrations were observed with advancing age.…”

Section: Age-specific Changessupporting

confidence: 91%

Changes of trace element status during aging: results of the EPIC-Potsdam cohort study

et al. 2019

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Purpose We aimed to evaluate age-dependent changes of six trace elements (TE) [manganese (Mn), iron (Fe), zinc (Zn), copper (Cu), iodine (I), and selenium (Se)] over a 20-year period. Methods TE concentrations were determined using repeated serum samples taken at baseline and after 20 years of follow-up from 219 healthy participants of the EPIC-Potsdam study, using inductively coupled plasma tandem mass spectrometry. For each TE, absolute and relative differences were calculated between the two time points, as well as the proportion of individuals within normal reference ranges. Interdependence between age-related TE differences was investigated using principal component analysis (PCA). Relationships between selected factors (lifestyle, sociodemographic, anthropometric factors, and hypertension) and corresponding TE longitudinal variability were examined using multivariable linear regression models.Results Median age of our study sample was 58.32 years (4.42) at baseline and 40% were females. Median Mn, Zn, Se concentrations and Se to Cu ratio significantly decreased during aging while median Fe, Cu, I concentrations and Cu to Zn ratio significantly increased. A substantial percentage of the participants, at both time points, had Zn concentrations below the reference range. The first PCA-extracted factor reflected the correlated decline in both Mn and Zn over time while the second factor reflected the observed (on average) increase in both Cu and I over time. Overall, none of the investigated factors were strong determinants of TE longitudinal variability, except possibly dietary supplement use, and alcohol use for Fe. Conclusions In conclusion, in this population-based study of healthy elderly, decrease in Mn, Zn, and Se concentrations and increase in Fe, Cu, and I concentrations were observed over 20 years of follow-up. Further research is required to investigate dietary determinants and markers of TE status as well as the relationships between TE profiles and the risk of age-related diseases.

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Section: Age-specific Changessupporting

confidence: 91%

Changes of trace element status during aging: results of the EPIC-Potsdam cohort study

et al. 2019

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“…Some of the changes that occur in the brain during aging have been ascribed to altered zinc homeostasis, as only 40% of elderly people have a sufficient zinc intake [147,195] . Impaired zinc homeostasis promotes immune dysfunction and has been associated with enhanced chronic inflammation dependent on the pathophysiological changes that occur with aging, rather than nutritional intake [196] . Thus, zinc has been suggested as a potential candidate to reverse age-associated changes leading to healthy aging through the reduction of inflammation [197] .…”

Section: Zinc (Zn)mentioning

confidence: 99%

Metal Toxicity Links to Alzheimer's Disease and Neuroinflammation

Huat

Camats-Perna

Newcombe

et al. 2019

Journal of Molecular Biology

327

180

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As the median age of the population increases, the number of individuals with Alzheimer's disease (AD) and the associated socioeconomic burden are predicted to worsen. While aging and inherent genetic predisposition play major roles in the onset of AD, lifestyle, physical fitness, medical condition, and social environment have emerged as relevant disease modifiers. These environmental risk factors can play a key role in accelerating or decelerating disease onset and progression. Among known environmental risk factors, chronic exposure to various metals has become more common among the public as the aggressive pace of anthropogenic activities releases excess amount of metals into the environment. As a result, we are exposed not only to essential metals, such as iron, copper, zinc and manganese, but also to toxic metals including lead, aluminum, and cadmium, which perturb metal homeostasis at the cellular and organismal levels. Herein, we review how these metals affect brain physiology and immunity, as well as their roles in the accumulation of toxic AD proteinaceous species (i.e., β-amyloid and tau). We also discuss studies that validate the disruption of immune-related pathways as an important mechanism of toxicity by which metals can contribute to AD. Our goal is to increase the awareness of metals as players in the onset and progression of AD.

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“…Besides the elderly, vegetarians or vegans and patients suffering from renal insufficiency or chronic diarrhea are affected by zinc deficiency [ 6 , 9 , 10 , 11 , 12 ]. In humans, clinical manifestations of zinc deficiency are similar to those observed in rodents and include weight loss, growth retardation, atrophy, and immune dysfunction, as well as increased oxidative stress and a boosted inflammatory immune response [ 3 , 13 , 14 , 15 , 16 ]. Dietary insufficiency and/or compromised uptake can result in perturbation of zinc homeostasis in humans [ 12 , 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

Zinc as a Gatekeeper of Immune Function

2017

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After the discovery of zinc deficiency in the 1960s, it soon became clear that zinc is essential for the function of the immune system. Zinc ions are involved in regulating intracellular signaling pathways in innate and adaptive immune cells. Zinc homeostasis is largely controlled via the expression and action of zinc “importers” (ZIP 1–14), zinc “exporters” (ZnT 1–10), and zinc-binding proteins. Anti-inflammatory and anti-oxidant properties of zinc have long been documented, however, underlying mechanisms are still not entirely clear. Here, we report molecular mechanisms underlying the development of a pro-inflammatory phenotype during zinc deficiency. Furthermore, we describe links between altered zinc homeostasis and disease development. Consequently, the benefits of zinc supplementation for a malfunctioning immune system become clear. This article will focus on underlying mechanisms responsible for the regulation of cellular signaling by alterations in zinc homeostasis. Effects of fast zinc flux, intermediate “zinc waves”, and late homeostatic zinc signals will be discriminated. Description of zinc homeostasis-related effects on the activation of key signaling molecules, as well as on epigenetic modifications, are included to emphasize the role of zinc as a gatekeeper of immune function.

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Main biomarkers associated with age-related plasma zinc decrease and copper/zinc ratio in healthy elderly from ZincAge study

Cited by 50 publications

References 54 publications

Changes of trace element status during aging: results of the EPIC-Potsdam cohort study

Changes of trace element status during aging: results of the EPIC-Potsdam cohort study

Metal Toxicity Links to Alzheimer's Disease and Neuroinflammation

Zinc as a Gatekeeper of Immune Function

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