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  Widespread Proteome Remodeling and Aggregation in Aging C-elegans

Walther, D. M., Kasturi, P., Zheng, M., Pinkert, S., Vecchi, G., Ciryam, P., et al. (2015). Widespread Proteome Remodeling and Aggregation in Aging C-elegans. Cell, 161(4), 919-932. doi:10.1016/j.cell.2015.03.032.

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CELL-D-14-02131R3.pdf (Postprint), 5MB
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CELL-D-14-02131R3.pdf
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 Creators:
Walther, Dirk M.1, Author              
Kasturi, Prasad2, Author              
Zheng, Min2, Author              
Pinkert, Stefan2, Author              
Vecchi, Giulia3, Author
Ciryam, Prajwal3, Author
Morimoto, Richard I.3, Author
Dobson, Christopher M.3, Author
Vendruscolo, Michele3, Author
Mann, Matthias1, Author              
Hartl, F. Ulrich2, Author              
Affiliations:
1Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565159              
2Hartl, Franz-Ulrich / Cellular Biochemistry, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565152              
3external, ou_persistent22              

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Free keywords: HEAT-SHOCK PROTEINS; CAENORHABDITIS-ELEGANS; MOLECULAR CHAPERONES; MISFOLDED PROTEINS; PROTEOTOXIC STRESS; GENE-EXPRESSION; AMINO-ACIDS; LIFE-SPAN; PROTEOSTASIS; LONGEVITY
 Abstract: Aging has been associated with a progressive decline of proteostasis, but how this process affects proteome composition remains largely unexplored. Here, we profiled more than 5,000 proteins along the lifespan of the nematode C. elegans. We find that one-third of proteins change in abundance at least 2-fold during aging, resulting in a severe proteome imbalance. These changes are reduced in the long-lived daf-2 mutant but are enhanced in the short-lived daf-16 mutant. While ribosomal proteins decline and lose normal stoichiometry, proteasome complexes increase. Proteome imbalance is accompanied by widespread protein aggregation, with abundant proteins that exceed solubility contributing most to aggregate load. Notably, the properties by which proteins are selected for aggregation differ in the daf-2 mutant, and an increased formation of aggregates associated with small heat-shock proteins is observed. We suggest that sequestering proteins into chaperone-enriched aggregates is a protective strategy to slow proteostasis decline during nematode aging.

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Language(s): eng - English
 Dates: 2014-10-232015-02-242015-05-072015
 Publication Status: Published in print
 Pages: 14
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Degree: -

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Project name : Toxic Protein AGgregation in Neurodegeneration (ToPAG) ERC-2012-SyG
Grant ID : 318987
Funding program : Funding Programme 7 (FP7)
Funding organization : European Commission (EC)

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Title: Cell
Source Genre: Journal
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Publ. Info: Cambridge, Mass. : Cell Press
Pages: - Volume / Issue: 161 (4) Sequence Number: - Start / End Page: 919 - 932 Identifier: ISSN: 0092-8674
CoNE: https://pure.mpg.de/cone/journals/resource/954925463183