title: Deep Proteome Analysis Identifies Age-Related Processes in C. elegans.
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 ∼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 ∼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.
authors.affiliation: Centre for Gene Regulation and Expression, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158-2517, USA; Calico Life Sciences, 1170 Veterans Boulevard, South San Francisco, CA 94080, USA.
authors.forename: Vikram
authors.initials: V
authors.lastname: Narayan
authors.affiliation: Centre for Gene Regulation and Expression, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
authors.forename: Tony
authors.initials: T
authors.lastname: Ly
authors.affiliation: Centre for Gene Regulation and Expression, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
authors.forename: Ehsan
authors.initials: E
authors.lastname: Pourkarimi
authors.affiliation: Centre for Gene Regulation and Expression, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
authors.forename: Alejandro Brenes
authors.initials: AB
authors.lastname: Murillo
authors.affiliation: Centre for Gene Regulation and Expression, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
authors.forename: Anton
authors.initials: A
authors.lastname: Gartner
authors.affiliation: Centre for Gene Regulation and Expression, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
authors.forename: Angus I
authors.initials: AI
authors.lastname: Lamond
authors.affiliation: Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158-2517, USA; Calico Life Sciences, 1170 Veterans Boulevard, South San Francisco, CA 94080, USA. Electronic address: cynthia@calicolabs.com.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Kenyon
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins; D020543:Proteome; D040901:Proteomics; D015398:Signal Transduction
chemical_list: D029742:Caenorhabditis elegans Proteins; D020543:Proteome