Cell aging preserves cellular immortality in the presence of lethal levels of damage

PLoS Biol. 2019 May 23;17(5):e3000266. doi: 10.1371/journal.pbio.3000266. eCollection 2019 May.

Abstract

Cellular aging, a progressive functional decline driven by damage accumulation, often culminates in the mortality of a cell lineage. Certain lineages, however, are able to sustain long-lasting immortality, as prominently exemplified by stem cells. Here, we show that Escherichia coli cell lineages exhibit comparable patterns of mortality and immortality. Through single-cell microscopy and microfluidic techniques, we find that these patterns are explained by the dynamics of damage accumulation and asymmetric partitioning between daughter cells. At low damage accumulation rates, both aging and rejuvenating lineages retain immortality by reaching their respective states of physiological equilibrium. We show that both asymmetry and equilibrium are present in repair mutants lacking certain repair chaperones, suggesting that intact repair capacity is not essential for immortal proliferation. We show that this growth equilibrium, however, is displaced by extrinsic damage in a dosage-dependent response. Moreover, we demonstrate that aging lineages become mortal when damage accumulation rates surpass a threshold, whereas rejuvenating lineages within the same population remain immortal. Thus, the processes of damage accumulation and partitioning through asymmetric cell division are essential in the determination of proliferative mortality and immortality in bacterial populations. This study provides further evidence for the characterization of cellular aging as a general process, affecting prokaryotes and eukaryotes alike and according to similar evolutionary constraints.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cell Lineage
  • Cell Polarity
  • Cell Proliferation
  • DNA Damage*
  • Escherichia coli / cytology*
  • Escherichia coli / growth & development
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism
  • Mutation / genetics
  • Protein Aggregates
  • Stress, Physiological

Substances

  • Escherichia coli Proteins
  • Protein Aggregates

Grants and funding

This work was supported by grants to L.C. from the National Science Foundation (DEB-1354253; https://nsf.gov/). A.M.P is supported by the Science Without Borders Fellowship / CAPES – Ministry of Education, Brazil (BEX 12987-13-1; https://capes.gov.br/), the Chris Wills Graduate Student Research Award, and the UC San Diego Goeddel Chancellor’s Award. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.