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Research Paper|Volume 6, Issue 11|pp 975—988

Iron promotes protein insolubility and aging in C. elegans

Ida M. Klang1,2, Birgit Schilling1, Dylan J. Sorensen1, Alexandria K. Sahu1, Pankaj Kapahi1, Julie K. Andersen1, Peter Swoboda2, David W. Killilea3, Bradford W. Gibson1,4, Gordon J. Lithgow1
  • 1The Buck Institute for Research on Aging, Novato, CA 94945, USA
  • 2Karolinska Institute, Department of Biosciences and Nutrition, S-141 83 Huddinge, Sweden
  • 3Nutrition and Metabolism Center, Children's Hospital Oakland Research Institute, Oakland, CA 94609, USA
  • 4Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94143, USA
Received: September 11, 2014Accepted: September 24, 2014Published: September 25, 2014
https://doi.org/10.18632/aging.100689

Copyright: © 2014 Klang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Many late-onset proteotoxic diseases are accompanied by a disruption in homeostasis of metals (metallostasis) including iron, copper and zinc. Although aging is the most prominent risk factor for these disorders, the impact of aging on metallostasis and its role in proteotoxic disease remain poorly understood. Moreover, it is not clear whether a loss of metallostasis influences normal aging. We have investigated the role of metallostasis in longevity of Caenorhabditis elegans. We found that calcium, copper, iron, and manganese levels increase as a function of age, while potassium and phosphorus levels tend to decrease. Increased dietary iron significantly accelerated the age-related accumulation of insoluble protein, a molecular pathology of aging. Proteomic analysis revealed widespread effects of dietary iron in multiple organelles and tissues. Pharmacological interventions to block accumulation of specific metals attenuated many models of proteotoxicity and extended normal lifespan. Collectively, these results suggest that a loss of metallostasis with aging contributes to age-related protein aggregation.