An aging-independent replicative lifespan in a symmetrically dividing eukaryote

  1. Eric C Spivey
  2. Stephen K Jones
  3. James R Rybarski
  4. Fatema A Saifuddin
  5. Ilya J Finkelstein  Is a corresponding author
  1. The University of Texas at Austin, United States

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.

Data availability

The following previously published data sets were used
    1. Wood et al.
    (2002) The genome sequence of Schizosaccharomyces pombe
    Publicly available at the NCBI Nucleotide (sccession no: CU329670.1).
    1. Wood et al.
    (2002) The genome sequence of Schizosaccharomyces pombe
    Publicly available at the NCBI Nucleotide (sccession no: CU329671.1).
    1. Wood et al.
    (2002) The genome sequence of Schizosaccharomyces pombe
    Publicly available at the NCBI Nucleotide (sccession no: CU329672.1).

Article and author information

Author details

  1. Eric C Spivey

    Department of Molecular Biosciences, The University of Texas at Austin, Austin, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4080-8616
  2. Stephen K Jones

    Department of Molecular Biosciences, The University of Texas at Austin, Austin, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. James R Rybarski

    Department of Molecular Biosciences, The University of Texas at Austin, Austin, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Fatema A Saifuddin

    Department of Molecular Biosciences, The University of Texas at Austin, Austin, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Ilya J Finkelstein

    Department of Molecular Biosciences, The University of Texas at Austin, Austin, United States
    For correspondence
    ifinkelstein@cm.utexas.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9371-2431

Funding

American Federation for Aging Research (AFAR-020)

  • Eric C Spivey
  • Stephen K Jones
  • James R Rybarski
  • Fatema A Saifuddin
  • Ilya J Finkelstein

National Institute on Aging (F32 AG053051)

  • Stephen K Jones

Cancer Prevention and Research Institute of Texas (R1214)

  • James R Rybarski
  • Fatema A Saifuddin
  • Ilya J Finkelstein

Welch Foundation (F-l808)

  • Eric C Spivey
  • Stephen K Jones
  • James R Rybarski
  • Fatema A Saifuddin
  • Ilya J Finkelstein

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Jeff Smith, University of Virginia, United States

Publication history

  1. Received: August 9, 2016
  2. Accepted: January 27, 2017
  3. Accepted Manuscript published: January 31, 2017 (version 1)
  4. Version of Record published: March 1, 2017 (version 2)
  5. Version of Record updated: April 12, 2018 (version 3)

Copyright

© 2017, Spivey et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 4,075
    Page views
  • 705
    Downloads
  • 23
    Citations

Article citation count generated by polling the highest count across the following sources: Scopus, Crossref, PubMed Central.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Eric C Spivey
  2. Stephen K Jones
  3. James R Rybarski
  4. Fatema A Saifuddin
  5. Ilya J Finkelstein
(2017)
An aging-independent replicative lifespan in a symmetrically dividing eukaryote
eLife 6:e20340.
https://doi.org/10.7554/eLife.20340

Further reading

    1. Cell Biology
    2. Chromosomes and Gene Expression
    Liangyu Zhang, Weston T Stauffer ... Abby F Dernburg
    Research Article

    Meiotic chromosome segregation relies on synapsis and crossover recombination between homologous chromosomes. These processes require multiple steps that are coordinated by the meiotic cell cycle and monitored by surveillance mechanisms. In diverse species, failures in chromosome synapsis can trigger a cell cycle delay and/or lead to apoptosis. How this key step in 'homolog engagement' is sensed and transduced by meiotic cells is unknown. Here we report that in C. elegans, recruitment of the Polo-like kinase PLK-2 to the synaptonemal complex triggers phosphorylation and inactivation of CHK-2, an early meiotic kinase required for pairing, synapsis, and double-strand break induction. Inactivation of CHK-2 terminates double-strand break formation and enables crossover designation and cell cycle progression. These findings illuminate how meiotic cells ensure crossover formation and accurate chromosome segregation.

    1. Cell Biology
    2. Physics of Living Systems
    Christa Ringers, Stephan Bialonski ... Nathalie Jurisch-Yaksi
    Research Article

    Motile cilia are hair-like cell extensions that beat periodically to generate fluid flow along various epithelial tissues within the body. In dense multiciliated carpets, cilia were shown to exhibit a remarkable coordination of their beat in the form of traveling metachronal waves, a phenomenon which supposedly enhances fluid transport. Yet, how cilia coordinate their regular beat in multiciliated epithelia to move fluids remains insufficiently understood, particularly due to lack of rigorous quantification. We combine experiments, novel analysis tools, and theory to address this knowledge gap. To investigate collective dynamics of cilia, we studied zebrafish multiciliated epithelia in the nose and the brain. We focused mainly on the zebrafish nose, due to its conserved properties with other ciliated tissues and its superior accessibility for non-invasive imaging. We revealed that cilia are synchronized only locally and that the size of local synchronization domains increases with the viscosity of the surrounding medium. Even though synchronization is local only, we observed global patterns of traveling metachronal waves across the zebrafish multiciliated epithelium. Intriguingly, these global wave direction patterns are conserved across individual fish, but different for left and right nose, unveiling a chiral asymmetry of metachronal coordination. To understand the implications of synchronization for fluid pumping, we used a computational model of a regular array of cilia. We found that local metachronal synchronization prevents steric collisions, cilia colliding with each other, and improves fluid pumping in dense cilia carpets, but hardly affects the direction of fluid flow. In conclusion, we show that local synchronization together with tissue-scale cilia alignment coincide and generate metachronal wave patterns in multiciliated epithelia, which enhance their physiological function of fluid pumping.