title: Zinc Levels Modulate Lifespan through Multiple Longevity Pathways in Caenorhabditis elegans.
abstract: 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.
authors.affiliation: The Buck Institute for Research on Aging, Novato, California, United States of America.|DBT-PU-IPLS Programme, Department of Botany/Biotechnology, Patna University, Patna- 800005, Bihar, India.
authors.forename: Jitendra
authors.initials: J
authors.lastname: Kumar
authors.affiliation: The Buck Institute for Research on Aging, Novato, California, United States of America.
authors.forename: Tracy
authors.initials: T
authors.lastname: Barhydt
authors.affiliation: Department of Biological Sciences, Birla Institute of Technology and Science, Rajasthan, India.
authors.forename: Anjali
authors.initials: A
authors.lastname: Awasthi
authors.affiliation: The Buck Institute for Research on Aging, Novato, California, United States of America.
authors.forename: Gordon J
authors.initials: GJ
authors.lastname: Lithgow
authors.affiliation: Nutrition & Metabolism Center, Children's Hospital of Oakland Research Institute, Oakland, California, United States of America.
authors.forename: David W
authors.initials: DW
authors.lastname: Killilea
authors.affiliation: The Buck Institute for Research on Aging, Novato, California, United States of America.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Kapahi
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000032:analysis / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000032:analysis / Q000378:metabolism; D007328:Insulin / Q000032:analysis / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000378:metabolism; D008136:Longevity; D066329:Protein Aggregates; D021381:Protein Transport; D015398:Signal Transduction; D015032:Zinc / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D007328:Insulin; D066329:Protein Aggregates; C108831:daf-16 protein, C elegans; D007334:Insulin-Like Growth Factor I; D015032:Zinc