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Zinc Levels Modulate Lifespan through Multiple Longevity Pathways in Caenorhabditis elegans

Zinc is an essential trace metal that has integral roles in numerous biological processes, including enzymatic function, protein structure, and cell signaling pathways. Both excess and deficiency of zinc can lead to detrimental effects on development and metabolism, resulting in abnormalities and di...

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Autores principales: Kumar, Jitendra, Barhydt, Tracy, Awasthi, Anjali, Lithgow, Gordon J., Killilea, David W., Kapahi, Pankaj
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4831763/
https://www.ncbi.nlm.nih.gov/pubmed/27078872
http://dx.doi.org/10.1371/journal.pone.0153513
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author Kumar, Jitendra
Barhydt, Tracy
Awasthi, Anjali
Lithgow, Gordon J.
Killilea, David W.
Kapahi, Pankaj
author_facet Kumar, Jitendra
Barhydt, Tracy
Awasthi, Anjali
Lithgow, Gordon J.
Killilea, David W.
Kapahi, Pankaj
author_sort Kumar, Jitendra
collection PubMed
description Zinc is an essential trace metal that has integral roles in numerous biological processes, including enzymatic function, protein structure, and cell signaling pathways. Both excess and deficiency of zinc can lead to detrimental effects on development and metabolism, resulting in abnormalities and disease. We altered the zinc balance within Caenorhabditis elegans to examine how changes in zinc burden affect longevity and healthspan in an invertebrate animal model. We found that increasing zinc levels in vivo with excess dietary zinc supplementation decreased the mean and maximum lifespan, whereas reducing zinc levels in vivo with a zinc-selective chelator increased the mean and maximum lifespan in C. elegans. We determined that the lifespan shortening effects of excess zinc required expression of DAF-16, HSF-1 and SKN-1 proteins, whereas the lifespan lengthening effects of the reduced zinc may be partially dependent upon this set of proteins. Furthermore, reducing zinc levels led to greater nuclear localization of DAF-16 and enhanced dauer formation compared to controls, suggesting that the lifespan effects of zinc are mediated in part by the insulin/IGF-1 pathway. Additionally, zinc status correlated with several markers of healthspan in worms, including proteostasis, locomotion and thermotolerance, with reduced zinc levels always associated with improvements in function. Taken together, these data support a role for zinc in regulating both development and lifespan in C. elegans, and that suggest that regulation of zinc homeostasis in the worm may be an example of antagonistic pleiotropy.
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spelling pubmed-48317632016-04-22 Zinc Levels Modulate Lifespan through Multiple Longevity Pathways in Caenorhabditis elegans Kumar, Jitendra Barhydt, Tracy Awasthi, Anjali Lithgow, Gordon J. Killilea, David W. Kapahi, Pankaj PLoS One Research Article Zinc is an essential trace metal that has integral roles in numerous biological processes, including enzymatic function, protein structure, and cell signaling pathways. Both excess and deficiency of zinc can lead to detrimental effects on development and metabolism, resulting in abnormalities and disease. We altered the zinc balance within Caenorhabditis elegans to examine how changes in zinc burden affect longevity and healthspan in an invertebrate animal model. We found that increasing zinc levels in vivo with excess dietary zinc supplementation decreased the mean and maximum lifespan, whereas reducing zinc levels in vivo with a zinc-selective chelator increased the mean and maximum lifespan in C. elegans. We determined that the lifespan shortening effects of excess zinc required expression of DAF-16, HSF-1 and SKN-1 proteins, whereas the lifespan lengthening effects of the reduced zinc may be partially dependent upon this set of proteins. Furthermore, reducing zinc levels led to greater nuclear localization of DAF-16 and enhanced dauer formation compared to controls, suggesting that the lifespan effects of zinc are mediated in part by the insulin/IGF-1 pathway. Additionally, zinc status correlated with several markers of healthspan in worms, including proteostasis, locomotion and thermotolerance, with reduced zinc levels always associated with improvements in function. Taken together, these data support a role for zinc in regulating both development and lifespan in C. elegans, and that suggest that regulation of zinc homeostasis in the worm may be an example of antagonistic pleiotropy. Public Library of Science 2016-04-14 /pmc/articles/PMC4831763/ /pubmed/27078872 http://dx.doi.org/10.1371/journal.pone.0153513 Text en © 2016 Kumar et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Kumar, Jitendra
Barhydt, Tracy
Awasthi, Anjali
Lithgow, Gordon J.
Killilea, David W.
Kapahi, Pankaj
Zinc Levels Modulate Lifespan through Multiple Longevity Pathways in Caenorhabditis elegans
title Zinc Levels Modulate Lifespan through Multiple Longevity Pathways in Caenorhabditis elegans
title_full Zinc Levels Modulate Lifespan through Multiple Longevity Pathways in Caenorhabditis elegans
title_fullStr Zinc Levels Modulate Lifespan through Multiple Longevity Pathways in Caenorhabditis elegans
title_full_unstemmed Zinc Levels Modulate Lifespan through Multiple Longevity Pathways in Caenorhabditis elegans
title_short Zinc Levels Modulate Lifespan through Multiple Longevity Pathways in Caenorhabditis elegans
title_sort zinc levels modulate lifespan through multiple longevity pathways in caenorhabditis elegans
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4831763/
https://www.ncbi.nlm.nih.gov/pubmed/27078872
http://dx.doi.org/10.1371/journal.pone.0153513
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