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Developmentally-programmed cellular senescence is conserved and widespread in zebrafish.

Sabela Da Silva-Álvarez1, Jorge Guerra-Varela2,3, Daniel Sobrido-Cameán4

  • 1Laboratory of Stem Cells in Cancer and Aging, Health Research Institute of Santiago de Compostela (IDIS), Xerencia de Xestión Integrada de Santiago (XXIS/SERGAS), Santiago de Compostela, Spain.

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Summary

Programmed cell senescence, a process usually linked to stress, is widespread in zebrafish embryos. This developmental cell senescence occurs in various organs and disappears with senolytic treatment, suggesting a conserved role in vertebrate development.

Keywords:
cellular senescencedevelopmentzebrafish

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Area of Science:

  • Developmental Biology
  • Cellular Biology

Background:

  • Cellular senescence typically acts as a stress response, halting cell cycles to prevent damaged cell proliferation.
  • Recent studies reveal programmed cell senescence during embryonic development in mice, birds, and amphibians, suggesting morphogenetic roles.
  • Fish have shown limited patterns of developmental cell senescence, prompting further investigation.

Purpose of the Study:

  • To investigate the conservation and extent of cellular senescence during zebrafish embryonic development.
  • To identify specific tissues and developmental stages where senescence occurs in zebrafish embryos.
  • To validate the senescent identity of these cells and explore the impact of senolytics.

Main Methods:

  • Detailed characterization of cellular senescence patterns in zebrafish embryos.
  • Treatment with the senolytic compound ABT-263 to assess its effect on identified senescent cells.
  • Histological and molecular analyses to confirm senescence markers and tissue distribution.

Main Results:

  • Cellular senescence was found to be conserved and widespread in zebrafish development, extending beyond previously known sites.
  • Senescence was identified in the central nervous system, intestine, liver, pronephric ducts, and crystalline, in addition to yolk and cloaca.
  • Treatment with ABT-263 eliminated senescence in these developing structures, confirming their senescent nature.

Conclusions:

  • Developmentally-programmed cell senescence is a conserved and widespread phenomenon in lower vertebrates like zebrafish.
  • These findings support the role of senescence in embryonic development and evolution.
  • Senolytic treatment offers a tool to study the functional contribution of developmental senescence.