title: High-resolution profiling of stationary-phase survival reveals yeast longevity factors and their genetic interactions.
abstract: Lifespan is influenced by a large number of conserved proteins and gene-regulatory pathways. Here, we introduce a strategy for systematically finding such longevity factors in Saccharomyces cerevisiae and scoring the genetic interactions (epistasis) among these factors. Specifically, we developed an automated competition-based assay for chronological lifespan, defined as stationary-phase survival of yeast populations, and used it to phenotype over 5,600 single- or double-gene knockouts at unprecedented quantitative resolution. We found that 14% of the viable yeast mutant strains were affected in their stationary-phase survival; the extent of true-positive chronological lifespan factors was estimated by accounting for the effects of culture aeration and adaptive regrowth. We show that lifespan extension by dietary restriction depends on the Swr1 histone-exchange complex and that a functional link between autophagy and the lipid-homeostasis factor Arv1 has an impact on cellular lifespan. Importantly, we describe the first genetic interaction network based on aging phenotypes, which successfully recapitulated the core-autophagy machinery and confirmed a role of the human tumor suppressor PTEN homologue in yeast lifespan and phosphatidylinositol phosphate metabolism. Our quantitative analysis of longevity factors and their genetic interactions provides insights into the gene-network interactions of aging cells.
authors.affiliation: Laboratorio Nacional de Genómica para la Biodiversidad, Centro de Investigación y de Estudios Avanzados del IPN, Irapuato, Guanajuato, Mexico.
authors.forename: Erika
authors.initials: E
authors.lastname: Garay
authors.affiliation: Laboratorio Nacional de Genómica para la Biodiversidad, Centro de Investigación y de Estudios Avanzados del IPN, Irapuato, Guanajuato, Mexico.
authors.forename: Sergio E
authors.initials: SE
authors.lastname: Campos
authors.affiliation: Laboratorio Nacional de Genómica para la Biodiversidad, Centro de Investigación y de Estudios Avanzados del IPN, Irapuato, Guanajuato, Mexico.
authors.forename: Jorge
authors.initials: J
authors.lastname: González de la Cruz
authors.affiliation: Laboratorio Nacional de Genómica para la Biodiversidad, Centro de Investigación y de Estudios Avanzados del IPN, Irapuato, Guanajuato, Mexico.
authors.forename: Ana P
authors.initials: AP
authors.lastname: Gaspar
authors.affiliation: Laboratorio Nacional de Genómica para la Biodiversidad, Centro de Investigación y de Estudios Avanzados del IPN, Irapuato, Guanajuato, Mexico.
authors.forename: Adrian
authors.initials: A
authors.lastname: Jinich
authors.affiliation: Laboratorio Nacional de Genómica para la Biodiversidad, Centro de Investigación y de Estudios Avanzados del IPN, Irapuato, Guanajuato, Mexico.
authors.forename: Alexander
authors.initials: A
authors.lastname: Deluna
mesh_terms: D001343:Autophagy / Q000235:genetics; D031204:Caloric Restriction; D002352:Carrier Proteins / Q000235:genetics; D016922:Cellular Senescence / Q000235:genetics*; D004843:Epistasis, Genetic; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D055786:Gene Knockout Techniques; D053263:Gene Regulatory Networks; D006706:Homeostasis; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics; D008136:Longevity / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000254:growth & development
chemical_list: C553399:ARV1 protein, human; D002352:Carrier Proteins; D008565:Membrane Proteins