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

Baudry, Julia; Kopp, Johannes; Boeing, Heiner; Kipp, Anna P.; Schwerdtle, Tanja; Schulze, Matthias B.

doi:10.1007/s00394-019-02143-w

Cited by 44 publications

(38 citation statements)

References 47 publications

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“…A reduction of Nrf2 levels and responsiveness is a relevant health condition that physiologically takes place during aging [38]. Thus, the question arises whether age-specific changes in TE profiles [39] might be related to Nrf2. Recently, it has been examined that Nrf2 activity levels strongly differ in the liver of male and female mice [40].…”

Section: Discussionmentioning

confidence: 99%

Crosstalk of Nrf2 with the Trace Elements Selenium, Iron, Zinc, and Copper

et al. 2019

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Trace elements, like Cu, Zn, Fe, or Se, are important for the proper functioning of antioxidant enzymes. However, in excessive amounts, they can also act as pro-oxidants. Accordingly, trace elements influence redox-modulated signaling pathways, such as the Nrf2 pathway. Vice versa, Nrf2 target genes belong to the group of transport and metal binding proteins. In order to investigate whether Nrf2 directly regulates the systemic trace element status, we used mice to study the effect of a constitutive, whole-body Nrf2 knockout on the systemic status of Cu, Zn, Fe, and Se. As the loss of selenoproteins under Se-deprived conditions has been described to further enhance Nrf2 activity, we additionally analyzed the combination of Nrf2 knockout with feeding diets that provide either suboptimal, adequate, or supplemented amounts of Se. Experiments revealed that the Nrf2 knockout partially affected the trace element concentrations of Cu, Zn, Fe, or Se in the intestine, liver, and/or plasma. However, aside from Fe, the other three trace elements were only marginally modulated in an Nrf2-dependent manner. Selenium deficiency mainly resulted in increased plasma Zn levels. One putative mediator could be the metal regulatory transcription factor 1, which was up-regulated with an increasing Se supply and downregulated in Se-supplemented Nrf2 knockout mice.

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Section: Discussionmentioning

confidence: 99%

Crosstalk of Nrf2 with the Trace Elements Selenium, Iron, Zinc, and Copper

et al. 2019

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“…Both Se deficiency and excess levels have been shown to influence the redox status and lead to severe adverse health consequences in animals and humans [10,21]. Interestingly, recently it has been demonstrated that plasma Se concentrations tend to decline in certain healthy human populations comprised of older subjects [22]. It was also reported that Se bioavailability was impacted by aging [13,23].…”

Section: Introductionmentioning

confidence: 99%

Dietary Selenium Supplementation Ameliorates Female Reproductive Efficiency in Aging Mice

et al. 2019

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Female reproductive (ovarian) aging is distinctively characterized by a markedly reduced reproductive function due to a remarkable decline in quality and quantity of follicles and oocytes. Selenium (Se) has been implicated in playing many important biological roles in male fertility and reproduction; however, its potential roles in female reproduction, particularly in aging subjects, remain poorly elucidated. Therefore, in the current study we used a murine model of female reproductive aging and elucidated how different Se-levels might affect the reproductive efficiency in aging females. Our results showed that at the end of an 8-week dietary trial, whole-blood Se concentration and blood total antioxidant capacity (TAOC) were significantly reduced in Se-deficient (0.08 mg Se/kg; Se-D) mice, whereas both of these biomarkers were significantly higher in inorganic (0.33 mg/kg; ISe-S) and organic (0.33 mg/kg; OSe-S) Se-supplemented groups. Similarly, compared to the Se-D group, Se supplementation significantly ameliorated the maintenance of follicles and reduced the rate of apoptosis in ovaries. Meanwhile, the rate of in vitro-produced embryos resulting from germinal vesicle (GV) oocytes was also significantly improved in Se-supplemented (ISe-S and OSe-S) groups compared to the Se-D mice, in which none of the embryos developed to the hatched blastocyst stage. RT-qPCR results revealed that mRNA expression of Gpx1, Gpx3, Gpx4, Selenof, p21, and Bcl-2 genes in ovaries of aging mice was differentially modulated by dietary Se levels. A considerably higher mRNA expression of Gpx1, Gpx3, Gpx4, and Selenof was observed in Se-supplemented groups compared to the Se-D group. Similarly, mRNA expression of Bcl-2 and p21 was significantly lower in Se-supplemented groups. Immunohistochemical assay also revealed a significantly higher expression of GPX4 in Se-supplemented mice. Our results reasonably indicate that Se deficiency (or marginal levels) can negatively impact the fertility and reproduction in females, particularly those of an advancing age, and that the Se supplementation (inorganic and organic) can substantiate ovarian function and overall reproductive efficiency in aging females.

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“…However, in vivo the effects were rather small under conditions of a mild modulation of the Cu status in the adequate to suboptimal concentration range in healthy, young mice. The average human serum concentration of Cu ranges from 15 to 31.5 μM [ [75] , [76] , [77] ], and thus concentrations used in cell culture experiments are adequate to supplemented. But under pathophysiological conditions up to 200 μM Cu were reported in serum [ 78 ].…”

Section: Discussionmentioning

confidence: 99%

“…Also under physiological conditions, serum Cu concentrations can be increased as recently described when comparing a subcohort of the EPIC Potsdam cohort which has been reinvited after 20 years. Advanced age was associated with increased Cu concentrations and decreased Se concentrations [ 76 ]. This indicates that an age-related decline in selenoprotein expression most probably is a result of a combination of lower Se concentrations and higher Cu concentration.…”

Section: Discussionmentioning

confidence: 99%

Copper interferes with selenoprotein synthesis and activity

et al. 2020

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Selenium and copper are essential trace elements for humans, needed for the biosynthesis of enzymes contributing to redox homeostasis and redox-dependent signaling pathways. Selenium is incorporated as selenocysteine into the active site of redox-relevant selenoproteins including glutathione peroxidases (GPX) and thioredoxin reductases (TXNRD). Copper-dependent enzymes mediate electron transfer and other redox reactions. As selenoprotein expression can be modulated e.g. by H 2 O 2 , we tested the hypothesis that copper status affects selenoprotein expression. To this end, hepatocarcinoma HepG2 cells and mice were exposed to a variable copper and selenium supply in a physiologically relevant concentration range, and transcript and protein expression as well as GPX and TXNRD activities were compared. Copper suppressed selenoprotein mRNA levels of GPX1 and SELENOW, downregulated GPX and TXNRD activities and decreased UGA recoding efficiency in reporter cells. The interfering effects were successfully suppressed by applying the copper chelators bathocuproinedisulfonic acid or tetrathiomolybdate. In mice, a decreased copper supply moderately decreased the copper status and negatively affected hepatic TXNRD activity. We conclude that there is a hitherto unknown interrelationship between copper and selenium status, and that copper negatively affects selenoprotein expression and activity most probably via limiting UGA recoding. This interference may be of physiological relevance during aging, where a particular shift in the selenium to copper ratio has been reported. An increased concentration of copper in face of a downregulated selenoprotein expression may synergize and negatively affect the cellular redox homeostasis contributing to disease processes.

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

Cited by 44 publications

References 47 publications

Crosstalk of Nrf2 with the Trace Elements Selenium, Iron, Zinc, and Copper

Crosstalk of Nrf2 with the Trace Elements Selenium, Iron, Zinc, and Copper

Dietary Selenium Supplementation Ameliorates Female Reproductive Efficiency in Aging Mice

Copper interferes with selenoprotein synthesis and activity

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