Moreno2019 - Stochastic model of G1 arrest due to proteostasis decline delimits replicative lifespan in yeast

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This model is described within the paper: A G1 arrest due to proteostasis decline delimits replicative lifespan in yeast
David F. Moreno, Kirsten Jenkins, Sandrine Morlot, Gilles Charvin, Attila Csikász-Nagy, Martí Aldea

To be implemented in Copasi.

Missing Event due to difficulties in SBML conversion to run model upon loading model in COPASI, create an event called Budding.
Set the trigger expression to: {Whi5.ParticleNumber} lt 250*({Whi5i.ParticleNumber}+{Whi5.ParticleNumber})/({Whi5.InitialParticleNumber}+{Whi5i.InitialParticleNumber}) AND {Values[Budding]} lt 1. 

Uncheck boxes for fire at initial time if true and trigger must remain true.

Leave priority box blank. 

Set delay to None.

There are 3 targets: 

the value of budding which should be set to one;

the time at budding which should be set to the time;

 and the unsynced generation which should be set to generation.

Related Publication
  • Proteostasis collapse, a hallmark of aging, hinders the chaperone-Start network and arrests cells in G1.
  • Moreno DF, Jenkins K, Morlot S, Charvin G, Attila Csikász-Nagy, Aldea M
  • eLife , 9/ 2019 , Volume 8 , PubMed ID: 31518229
  • Molecular Biology Institute of Barcelona (IBMB), CSIC, Barcelona, Spain.
  • Loss of proteostasis and cellular senescence are key hallmarks of aging, but direct cause-effect relationships are not well understood. We show that most yeast cells arrest in G1 before death with low nuclear levels of Cln3, a key G1 cyclin extremely sensitive to chaperone status. Chaperone availability is seriously compromised in aged cells, and the G1 arrest coincides with massive aggregation of a metastable chaperone-activity reporter. Moreover, G1-cyclin overexpression increases lifespan in a chaperone-dependent manner. As a key prediction of a model integrating autocatalytic protein aggregation and a minimal Start network, enforced protein aggregation causes a severe reduction in lifespan, an effect that is greatly alleviated by increased expression of specific chaperones or cyclin Cln3. Overall, our data show that proteostasis breakdown, by compromising chaperone activity and G1-cyclin function, causes an irreversible arrest in G1, configuring a molecular pathway postulating proteostasis decay as a key contributing effector of cell senescence.
Kirsten Jenkins, Krishna Kumar Tiwari

Metadata information

Curation status

Name Description Size Actions

Model files

CellCycleProteinAggregation.xml SBML_LV2V4_representation_of_yeast_aging_by_protein_aggregates 220.71 KB Preview | Download

Additional files

ProteinAggregationCellCycle.cps Cps_file_for_model_of_yeast_by_protein_aggregates 248.27 KB Preview | Download

  • Model originally submitted by : Kirsten Jenkins
  • Submitted: Nov 29, 2019 10:01:26 AM
  • Last Modified: Nov 29, 2019 10:01:26 AM
  • Version: 5 public model Download this version
    • Submitted on: Nov 29, 2019 10:01:26 AM
    • Submitted by: Krishna Kumar Tiwari
    • With comment: Edited model metadata online.
: Variable used inside SBML models

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