Iron promotes protein insolubility and aging in <i>C. elegans</i>

Ida M. Klang; Birgit Schilling; Dylan J. Sorensen; Alexandria K. Sahu; Pankaj Kapahi; Julie K. Andersen; Peter Swoboda; David W. Killilea; Bradford W. Gibson; Gordon J. Lithgow

doi:doi:10.18632/aging.100689

Research Paper Volume 6, Issue 11 pp 975—988

Iron promotes protein insolubility and aging in C. elegans

Ida M. Klang^1,2,, Birgit Schilling^1,, Dylan J. Sorensen^1,, Alexandria K. Sahu^1,, Pankaj Kapahi^1,, Julie K. Andersen^1,, Peter Swoboda^2,, David W. Killilea^3,, Bradford W. Gibson^1,4,, Gordon J. Lithgow^1,,

¹ The Buck Institute for Research on Aging, Novato, CA 94945, USA
² Karolinska Institute, Department of Biosciences and Nutrition, S-141 83 Huddinge, Sweden
³ Nutrition and Metabolism Center, Children's Hospital Oakland Research Institute, Oakland, CA 94609, USA
⁴ Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94143, USA

https://doi.org/10.18632/aging.100689
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Klang IM, Schilling B, Sorensen DJ, Sahu AK, Kapahi P, Andersen JK, Swoboda P, Killilea DW, Gibson BW, Lithgow GJ, . Iron promotes protein insolubility and aging in C. elegans. Aging (Albany NY). 2014; 6:975-988. https://doi.org/10.18632/aging.100689

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Provider: 
        TY  - JOUR
        AU  - Klang, Ida M. 
        AU  - Schilling, Birgit 
        AU  - Sorensen, Dylan J. 
        AU  - Sahu, Alexandria K. 
        AU  - Kapahi, Pankaj 
        AU  - Andersen, Julie K. 
        AU  - Swoboda, Peter 
        AU  - Killilea, David W. 
        AU  - Gibson, Bradford W. 
        AU  - Lithgow, Gordon J. 
        TI  - Iron promotes protein insolubility and aging in <i>C. elegans</i>
        JO  - 
        JA  - Aging (Albany NY)
        VL  - 6
        IS  - 11
        PB  - 
        SN  - 
        UR  - https://doi.org/10.18632/aging.100689
        DO  - 10.18632/aging.100689
        SP  - 975
        EP  - 988
        PY  - 
        AB  - 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.
        ER  -

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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.