title: Parallel profiling of fission yeast deletion mutants for proliferation and for lifespan during long-term quiescence.
abstract: Genetic factors underlying aging are remarkably conserved from yeast to human. The fission yeast Schizosaccharomyces pombe is an emerging genetic model to analyze cellular aging. Chronological lifespan (CLS) has been studied in stationary-phase yeast cells depleted for glucose, which only survive for a few days. Here, we analyzed CLS in quiescent S. pombe cells deprived of nitrogen, which arrest in a differentiated, G0-like state and survive for more than 2 months. We applied parallel mutant phenotyping by barcode sequencing (Bar-seq) to assay pooled haploid deletion mutants as they aged together during long-term quiescence. As expected, mutants with defects in autophagy or quiescence were under-represented or not detected. Lifespan scores could be calculated for 1199 mutants. We focus the discussion on the 48 most long-lived mutants, including both known aging genes in other model systems and genes not previously implicated in aging. Genes encoding membrane proteins were particularly prominent as pro-aging factors. We independently verified the extended CLS in individual assays for 30 selected mutants, showing the efficacy of the screen. We also applied Bar-seq to profile all pooled deletion mutants for proliferation under a standard growth condition. Unlike for stationary-phase cells, no inverse correlation between growth and CLS of quiescent cells was evident. These screens provide a rich resource for further studies, and they suggest that the quiescence model can provide unique, complementary insights into cellular aging.
authors.affiliation: University College London, Research Department of Genetics, Evolution & Environment and Institute of Healthy Aging, Gower Street, Darwin Building, London WC1E 6BT, UK.
authors.forename: Theodora
authors.initials: T
authors.lastname: Sideri
authors.affiliation: University College London, Research Department of Genetics, Evolution & Environment and Institute of Healthy Aging, Gower Street, Darwin Building, London WC1E 6BT, UK.
authors.forename: Charalampos
authors.initials: C
authors.lastname: Rallis
authors.affiliation: University College London, Research Department of Genetics, Evolution & Environment and Institute of Healthy Aging, Gower Street, Darwin Building, London WC1E 6BT, UK.
authors.forename: Danny A
authors.initials: DA
authors.lastname: Bitton
authors.affiliation: University College London, Research Department of Genetics, Evolution & Environment and Institute of Healthy Aging, Gower Street, Darwin Building, London WC1E 6BT, UK.
authors.forename: Bruno M
authors.initials: BM
authors.lastname: Lages
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Suo
authors.affiliation: University College London, Research Department of Genetics, Evolution & Environment and Institute of Healthy Aging, Gower Street, Darwin Building, London WC1E 6BT, UK.
authors.forename: María
authors.initials: M
authors.lastname: Rodríguez-López
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China.
authors.forename: Li-Lin
authors.initials: LL
authors.lastname: Du
authors.affiliation: University College London, Research Department of Genetics, Evolution & Environment and Institute of Healthy Aging, Gower Street, Darwin Building, London WC1E 6BT, UK j.bahler@ucl.ac.uk.
authors.forename: Jürg
authors.identifier: http://orcid.org/0000-0003-4036-1532
authors.initials: J
authors.lastname: Bähler
mesh_terms: D058893:DNA Barcoding, Taxonomic; D004271:DNA, Fungal / Q000235:genetics; D009154:Mutation; D012568:Schizosaccharomyces / Q000235:genetics* / Q000254:growth & development
chemical_list: D004271:DNA, Fungal
keywords: G0 phase; cellular aging; competitive growth; longevity; quiescence