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Iron promotes protein insolubility and aging in C. elegans
- Source :
- Aging (Albany NY), Scopus-Elsevier, Karolinska Institutet
- Publication Year :
- 2014
- Publisher :
- Impact Journals, LLC, 2014.
-
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.
- Subjects :
- Proteomics
Aging
Time Factors
Iron
media_common.quotation_subject
chemistry.chemical_element
Calcium
Protein aggregation
protein aggregation
Protein Aggregates
Organelle
Animals
Homeostasis
Caenorhabditis elegans
Caenorhabditis elegans Proteins
Chelating Agents
media_common
Dietary iron
biology
Age Factors
Longevity
Cell Biology
biology.organism_classification
Diet
Cell biology
Solubility
Proteotoxicity
chemistry
C. elegans
metal homeostasis
lifespan
Research Paper
Subjects
Details
- ISSN :
- 19454589
- Volume :
- 6
- Database :
- OpenAIRE
- Journal :
- Aging
- Accession number :
- edsair.doi.dedup.....e28909e379cff0e56fa393ed1e2a1fce
- Full Text :
- https://doi.org/10.18632/aging.100689