Nutritive Manganese and Zinc Overdosing in Aging C. elegans Result in a Metallothionein-Mediated Alteration in Metal Homeostasis

Jessica Baesler; Vivien Michaelis; Michael Stiboller; Hajo Haase; Michael Aschner; Tanja Schwerdtle; Stephen R. Sturzenbaum; Julia Bornhorst

doi:10.1002/mnfr.202001176

Nutritive Manganese and Zinc Overdosing in Aging C. elegans Result in a Metallothionein-Mediated Alteration in Metal Homeostasis

Jessica Baesler, Vivien Michaelis, Michael Stiboller, Hajo Haase, Michael Aschner, Tanja Schwerdtle, Stephen R. Sturzenbaum, Julia Bornhorst^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

9 Citations (Scopus)

Abstract

Scope: Manganese (Mn) and zinc (Zn) are not only essential trace elements, but also potential exogenous risk factors for various diseases. Since the disturbed homeostasis of single metals can result in detrimental health effects, concerns have emerged regarding the consequences of excessive exposures to multiple metals, either via nutritional supplementation or parenteral nutrition. This study focuses on Mn-Zn-interactions in the nematode Caenorhabditis elegans (C. elegans) model, taking into account aspects related to aging and age-dependent neurodegeneration. Methods and Results: Chronic co-exposure of C. elegans to Mn and Zn increases metal uptake, exceeding levels of single metal exposures. Supplementation with Mn and/or Zn also leads to an age-dependent increase in metal content, a decline in overall mRNA expression, and metal co-supplementation induced expression of target genes involved in Mn and Zn homeostasis, in particular metallothionein 1 (mtl-1). Studies in transgenic worms reveal that mtl-1 played a prominent role in mediating age- and diet-dependent alterations in metal homeostasis. Metal dyshomeostasis is further induced in parkin-deficient nematodes (Parkinson's disease (PD) model), but this did not accelerate the age-dependent dopaminergic neurodegeneration. Conclusions: A nutritive overdose of Mn and Zn can alter interactions between essential metals in an aging organism, and metallothionein 1 acts as a potential protective modulator in regulating homeostasis.

Original language	English
Article number	2001176
Journal	Molecular Nutrition and Food Research
Volume	65
Issue number	8
DOIs	https://doi.org/10.1002/mnfr.202001176
Publication status	Published - Apr 2021

Keywords

aging
C. elegans
homeostasis
manganese
zinc

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10.1002/mnfr.202001176

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@article{e9f1cd2909de4e03b5e91654edb4ee13,

title = "Nutritive Manganese and Zinc Overdosing in Aging C. elegans Result in a Metallothionein-Mediated Alteration in Metal Homeostasis",

abstract = "Scope: Manganese (Mn) and zinc (Zn) are not only essential trace elements, but also potential exogenous risk factors for various diseases. Since the disturbed homeostasis of single metals can result in detrimental health effects, concerns have emerged regarding the consequences of excessive exposures to multiple metals, either via nutritional supplementation or parenteral nutrition. This study focuses on Mn-Zn-interactions in the nematode Caenorhabditis elegans (C. elegans) model, taking into account aspects related to aging and age-dependent neurodegeneration. Methods and Results: Chronic co-exposure of C. elegans to Mn and Zn increases metal uptake, exceeding levels of single metal exposures. Supplementation with Mn and/or Zn also leads to an age-dependent increase in metal content, a decline in overall mRNA expression, and metal co-supplementation induced expression of target genes involved in Mn and Zn homeostasis, in particular metallothionein 1 (mtl-1). Studies in transgenic worms reveal that mtl-1 played a prominent role in mediating age- and diet-dependent alterations in metal homeostasis. Metal dyshomeostasis is further induced in parkin-deficient nematodes (Parkinson's disease (PD) model), but this did not accelerate the age-dependent dopaminergic neurodegeneration. Conclusions: A nutritive overdose of Mn and Zn can alter interactions between essential metals in an aging organism, and metallothionein 1 acts as a potential protective modulator in regulating homeostasis.",

keywords = "aging, C. elegans, homeostasis, manganese, zinc",

author = "Jessica Baesler and Vivien Michaelis and Michael Stiboller and Hajo Haase and Michael Aschner and Tanja Schwerdtle and Sturzenbaum, {Stephen R.} and Julia Bornhorst",

note = "Funding Information: The authors thank the DFG Research Unit TraceAge (FOR 2558, BO4103/4-1, HA4318/4-1) for supporting this work. Some strains were provided by the CGC, which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440). M.A. was supported in part by grants from the National Institute of Environmental Health Sciences (NIEHS) R01ES07331 and R01ES10563. Publisher Copyright: {\textcopyright} 2021 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH GmbH Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2021",

month = apr,

doi = "10.1002/mnfr.202001176",

language = "English",

volume = "65",

journal = "Molecular Nutrition and Food Research",

issn = "1613-4125",

publisher = "Wiley-VCH Verlag",

number = "8",

}

TY - JOUR

T1 - Nutritive Manganese and Zinc Overdosing in Aging C. elegans Result in a Metallothionein-Mediated Alteration in Metal Homeostasis

AU - Baesler, Jessica

AU - Michaelis, Vivien

AU - Stiboller, Michael

AU - Haase, Hajo

AU - Aschner, Michael

AU - Schwerdtle, Tanja

AU - Sturzenbaum, Stephen R.

AU - Bornhorst, Julia

N1 - Funding Information: The authors thank the DFG Research Unit TraceAge (FOR 2558, BO4103/4-1, HA4318/4-1) for supporting this work. Some strains were provided by the CGC, which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440). M.A. was supported in part by grants from the National Institute of Environmental Health Sciences (NIEHS) R01ES07331 and R01ES10563. Publisher Copyright: © 2021 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH GmbH Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/4

Y1 - 2021/4

N2 - Scope: Manganese (Mn) and zinc (Zn) are not only essential trace elements, but also potential exogenous risk factors for various diseases. Since the disturbed homeostasis of single metals can result in detrimental health effects, concerns have emerged regarding the consequences of excessive exposures to multiple metals, either via nutritional supplementation or parenteral nutrition. This study focuses on Mn-Zn-interactions in the nematode Caenorhabditis elegans (C. elegans) model, taking into account aspects related to aging and age-dependent neurodegeneration. Methods and Results: Chronic co-exposure of C. elegans to Mn and Zn increases metal uptake, exceeding levels of single metal exposures. Supplementation with Mn and/or Zn also leads to an age-dependent increase in metal content, a decline in overall mRNA expression, and metal co-supplementation induced expression of target genes involved in Mn and Zn homeostasis, in particular metallothionein 1 (mtl-1). Studies in transgenic worms reveal that mtl-1 played a prominent role in mediating age- and diet-dependent alterations in metal homeostasis. Metal dyshomeostasis is further induced in parkin-deficient nematodes (Parkinson's disease (PD) model), but this did not accelerate the age-dependent dopaminergic neurodegeneration. Conclusions: A nutritive overdose of Mn and Zn can alter interactions between essential metals in an aging organism, and metallothionein 1 acts as a potential protective modulator in regulating homeostasis.

AB - Scope: Manganese (Mn) and zinc (Zn) are not only essential trace elements, but also potential exogenous risk factors for various diseases. Since the disturbed homeostasis of single metals can result in detrimental health effects, concerns have emerged regarding the consequences of excessive exposures to multiple metals, either via nutritional supplementation or parenteral nutrition. This study focuses on Mn-Zn-interactions in the nematode Caenorhabditis elegans (C. elegans) model, taking into account aspects related to aging and age-dependent neurodegeneration. Methods and Results: Chronic co-exposure of C. elegans to Mn and Zn increases metal uptake, exceeding levels of single metal exposures. Supplementation with Mn and/or Zn also leads to an age-dependent increase in metal content, a decline in overall mRNA expression, and metal co-supplementation induced expression of target genes involved in Mn and Zn homeostasis, in particular metallothionein 1 (mtl-1). Studies in transgenic worms reveal that mtl-1 played a prominent role in mediating age- and diet-dependent alterations in metal homeostasis. Metal dyshomeostasis is further induced in parkin-deficient nematodes (Parkinson's disease (PD) model), but this did not accelerate the age-dependent dopaminergic neurodegeneration. Conclusions: A nutritive overdose of Mn and Zn can alter interactions between essential metals in an aging organism, and metallothionein 1 acts as a potential protective modulator in regulating homeostasis.

KW - aging

KW - C. elegans

KW - homeostasis

KW - manganese

KW - zinc

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U2 - 10.1002/mnfr.202001176

DO - 10.1002/mnfr.202001176

M3 - Article

AN - SCOPUS:85102241562

SN - 1613-4125

VL - 65

JO - Molecular Nutrition and Food Research

JF - Molecular Nutrition and Food Research

IS - 8

M1 - 2001176

ER -

Nutritive Manganese and Zinc Overdosing in Aging C. elegans Result in a Metallothionein-Mediated Alteration in Metal Homeostasis

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