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Aging (Albany NY). 2014 Nov;6(11):975-91.

Iron promotes protein insolubility and aging in C. elegans.

Author information

1
The Buck Institute for Research on Aging, Novato, CA 94945, USA. Karolinska Institute, Department of Biosciences and Nutrition, S-141 83 Huddinge, Sweden.
2
The Buck Institute for Research on Aging, Novato, CA 94945, USA.
3
Karolinska Institute, Department of Biosciences and Nutrition, S-141 83 Huddinge, Sweden.
4
Nutrition and Metabolism Center, Children's Hospital Oakland Research Institute, Oakland, CA 94609, USA.
5
The Buck Institute for Research on Aging, Novato, CA 94945, USA. Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94143, USA.

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 ofCaenorhabditis 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.

PMID:
25554795
PMCID:
PMC4276790
DOI:
10.18632/aging.100689
[Indexed for MEDLINE]
Free PMC Article

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