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.
journal_name
Celljournal_title
Cellauthors
Walther DM,Kasturi P,Zheng M,Pinkert S,Vecchi G,Ciryam P,Morimoto RI,Dobson CM,Vendruscolo M,Mann M,Hartl FUdoi
10.1016/j.cell.2015.03.032subject
Has Abstractpub_date
2015-05-07 00:00:00pages
919-32issue
4eissn
0092-8674issn
1097-4172pii
S0092-8674(15)00320-7journal_volume
161pub_type
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