title: Protein biogenesis machinery is a driver of replicative aging in yeast.
abstract: An integrated account of the molecular changes occurring during the process of cellular aging is crucial towards understanding the underlying mechanisms. Here, using novel culturing and computational methods as well as latest analytical techniques, we mapped the proteome and transcriptome during the replicative lifespan of budding yeast. With age, we found primarily proteins involved in protein biogenesis to increase relative to their transcript levels. Exploiting the dynamic nature of our data, we reconstructed high-level directional networks, where we found the same protein biogenesis-related genes to have the strongest ability to predict the behavior of other genes in the system. We identified metabolic shifts and the loss of stoichiometry in protein complexes as being consequences of aging. We propose a model whereby the uncoupling of protein levels of biogenesis-related genes from their transcript levels is causal for the changes occurring in aging yeast. Our model explains why targeting protein synthesis, or repairing the downstream consequences, can serve as interventions in aging.
authors.affiliation: European Research Institute for the Biology of Ageing, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Georges E
authors.initials: GE
authors.lastname: Janssens
authors.affiliation: Molecular Systems Biology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, The Netherlands.
authors.forename: Anne C
authors.initials: AC
authors.lastname: Meinema
authors.affiliation: Probability and Statistics, Johann Bernoulli Institute of Mathematics and Computer Science, University of Groningen, Groningen, The Netherlands.
authors.forename: Javier
authors.initials: J
authors.lastname: González
authors.affiliation: Analytical Biochemistry, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, The Netherlands.
authors.forename: Justina C
authors.initials: JC
authors.lastname: Wolters
authors.affiliation: Biozentrum, University of Basel, Basel, Switzerland.
authors.forename: Alexander
authors.initials: A
authors.lastname: Schmidt
authors.affiliation: European Research Institute for the Biology of Ageing, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Victor
authors.initials: V
authors.lastname: Guryev
authors.affiliation: Analytical Biochemistry, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, The Netherlands.
authors.forename: Rainer
authors.initials: R
authors.lastname: Bischoff
authors.affiliation: Probability and Statistics, Johann Bernoulli Institute of Mathematics and Computer Science, University of Groningen, Groningen, The Netherlands.
authors.forename: Ernst C
authors.initials: EC
authors.lastname: Wit
authors.affiliation: European Research Institute for the Biology of Ageing, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Liesbeth M
authors.initials: LM
authors.lastname: Veenhoff
authors.affiliation: Molecular Systems Biology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, The Netherlands.
authors.forename: Matthias
authors.initials: M
authors.lastname: Heinemann
mesh_terms: D016922:Cellular Senescence; D020869:Gene Expression Profiling; D008954:Models, Biological; D020543:Proteome / Q000032:analysis; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000096:biosynthesis*
chemical_list: D020543:Proteome; D029701:Saccharomyces cerevisiae Proteins
keywords: S. cerevisiae; biochemistry; computational biology; proteome; replicative aging; systems biology; transcriptome