title: An aging-independent replicative lifespan in a symmetrically dividing eukaryote.
abstract: The replicative lifespan (RLS) of a cell-defined as the number of cell divisions before death-has informed our understanding of the mechanisms of cellular aging. However, little is known about aging and longevity in symmetrically dividing eukaryotic cells because most prior studies have used budding yeast for RLS studies. Here, we describe a multiplexed fission yeast lifespan micro-dissector (multFYLM) and an associated image processing pipeline for performing high-throughput and automated single-cell micro-dissection. Using the multFYLM, we observe continuous replication of hundreds of individual fission yeast cells for over seventy-five generations. Surprisingly, cells die without the classic hallmarks of cellular aging, such as progressive changes in size, doubling time, or sibling health. Genetic perturbations and drugs can extend the RLS via an aging-independent mechanism. Using a quantitative model to analyze these results, we conclude that fission yeast does not age and that cellular aging and replicative lifespan can be uncoupled in a eukaryotic cell.
authors.affiliation: Department of Molecular Biosciences, The University of Texas at Austin, Austin, United States.|Center for Systems and Synthetic Biology, The University of Texas at Austin, Austin, United States.
authors.forename: Eric C
authors.identifier: http://orcid.org/0000-0002-4080-8616
authors.initials: EC
authors.lastname: Spivey
authors.affiliation: Department of Molecular Biosciences, The University of Texas at Austin, Austin, United States.|Center for Systems and Synthetic Biology, The University of Texas at Austin, Austin, United States.
authors.forename: Stephen K
authors.initials: SK
authors.lastname: Jones
authors.affiliation: Department of Molecular Biosciences, The University of Texas at Austin, Austin, United States.
authors.forename: James R
authors.initials: JR
authors.lastname: Rybarski
authors.affiliation: Department of Molecular Biosciences, The University of Texas at Austin, Austin, United States.
authors.forename: Fatema A
authors.initials: FA
authors.lastname: Saifuddin
authors.affiliation: Department of Molecular Biosciences, The University of Texas at Austin, Austin, United States.|Center for Systems and Synthetic Biology, The University of Texas at Austin, Austin, United States.|Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, United States.
authors.forename: Ilya J
authors.identifier: http://orcid.org/0000-0002-9371-2431
authors.initials: IJ
authors.lastname: Finkelstein
mesh_terms: D002455:Cell Division; D004261:DNA Replication; D050296:Microbial Viability; D008828:Microbiological Techniques; D044085:Microfluidics; D012568:Schizosaccharomyces / Q000502:physiology*; D059010:Single-Cell Analysis; D013997:Time Factors
keywords: S. pombe; aging; biophysics; cell biology; fission yeast; microfluidics; microscopy; replicative lifespan; single cell; structural biology