Deep Proteome Analysis Identifies Age-Related Processes in C. elegans

Vikram Narayan, Tony Ly, Ehsan Pourkarimi, Alejandro Brenes Murillo, Anton Gartner, Angus Lamond, Cynthia Kenyon (Lead / Corresponding author)

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    69 Citations (Scopus)
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    Effective network analysis of protein data requires high-quality proteomic datasets. Here, we report a near doubling in coverage of the C. elegans adult proteome, identifying >11,000 proteins in total with 9,400 proteins reproducibly detected in three biological replicates. Using quantitative mass spectrometry, weidentify proteinswhose abundances vary with aging, revealing a concerted downregulation of proteins involved in specific metabolic pathways and cellular stress responses with advancing age. Among these are 30 peroxisomal proteins, including the PRX-5/PEX5 import protein. Functional experiments confirm that protein import into the peroxisome is compromised in vivo in old animals. We also studied the behavior of the set of age-variant proteins in chronologically age-matched, long-lived daf-2 insulin/IGF-1-pathway mutants. Unexpectedly, the levels of many of these age-variant proteins did not scale with extended lifespan. This indicates that, despite their youthful appearance and extended lifespans, not all aspects of aging are reset in these daf-2 mutants.
    Original languageEnglish
    Pages (from-to)144-159
    Number of pages15
    JournalCell Systems
    Issue number2
    Early online date21 Jul 2016
    Publication statusPublished - 24 Aug 2016


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