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

Vikram Narayan, Tony Ly, Ehsan Pourkarimi, Alejandro Brenes Murillo, Anton Gartner, Angus I Lamond, Cynthia Kenyon*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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 similar to 9,400 proteins reproducibly detected in three biological replicates. Using quantitative mass spectrometry, we identify proteins whose abundances vary with age, revealing a concerted downregulation of proteins involved in specific metabolic pathways and upregulation of cellular stress responses with advancing age. Among these are similar to 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 long-lived mutants.

Original languageEnglish
Pages (from-to)144-159
Number of pages16
JournalCell Systems
Volume3
Issue number2
DOIs
Publication statusPublished - 24 Aug 2016

Keywords

  • LIFE-SPAN REGULATION
  • HEAT-SHOCK FACTOR
  • CAENORHABDITIS-ELEGANS
  • SACCHAROMYCES-CEREVISIAE
  • LONGEVITY
  • GENES
  • GENETICS
  • MASS
  • INTERFERENCE
  • EXPRESSION

Cite this