Widespread proteome remodeling and aggregation in aging C. elegans

Dirk M. Walther, Prasad Kasturi, Min Zheng, Stefan Pinkert, Giulia Vecchi, Prajwal Ciryam, Richard I Morimoto, Christopher M. Dobson, Michele Vendruscolo, Matthias Mann, F. Ulrich Hartl*

*Corresponding author for this work

Research output: Contribution to journalArticle

244 Scopus citations

Abstract

Agin1g 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.

Original languageEnglish (US)
Pages (from-to)919-932
Number of pages14
JournalCell
Volume161
Issue number4
DOIs
StatePublished - May 7 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Walther, D. M., Kasturi, P., Zheng, M., Pinkert, S., Vecchi, G., Ciryam, P., Morimoto, R. I., Dobson, C. M., Vendruscolo, M., Mann, M., & Hartl, F. U. (2015). Widespread proteome remodeling and aggregation in aging C. elegans. Cell, 161(4), 919-932. https://doi.org/10.1016/j.cell.2015.03.032