Connective tissue fibroblasts from highly regenerative mammals are refractory to ROS-induced cellular senescence

Sandeep Saxena, Hemendra Vekaria, Patrick G. Sullivan, Ashley W. Seifert

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

A surveillance system in mammals constantly monitors cell activity to protect against aberrant proliferation in response to damage, injury and oncogenic stress. Here we isolate and culture connective tissue fibroblasts from highly regenerative mammals (Acomys and Oryctolagus) to determine how these cells interpret signals that normally induce cellular senescence in non-regenerating mammals (Mus and Rattus). While H2O2 exposure substantially decreases cell proliferation and increases p53, p21, p16, and p19 in cells from mice and rats, cells from spiny mice and rabbits are highly resistant to H2O2. Quantifying oxygen consumption and mitochondrial stability, we demonstrate that increased intracellular H2O2 is rapidly detoxified in regenerating species, but overwhelms antioxidant scavenging in cells from non-regenerative mammals. However, pretreatment with N-acetylcysteine (NAC) protects mouse and rat cells from ROS-induced cellular senescence. Collectively, our results show that intrinsic cellular differences in stress-sensing mechanisms partially explain interspecific variation in regenerative ability.

Original languageEnglish
Article number4400
JournalNature Communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

Bibliographical note

Publisher Copyright:
© 2019, The Author(s).

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy

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