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Updated: Jun 27, 2026

Techniques to Induce and Quantify Cellular Senescence
06:51

Techniques to Induce and Quantify Cellular Senescence

Published on: May 1, 2017

Interferon-gamma induces cellular senescence through p53-dependent DNA damage signaling in human endothelial cells

Kwang Seok Kim1, Kyung Won Kang, Young Bae Seu

  • 1Department of Biochemistry and Molecular Biology, College of Medicine, Yeungnam University, Daegu 705-717, Republic of Korea.

Mechanisms of Ageing and Development
|December 17, 2008
PubMed

Insights

Interferon-gamma (IFN-gamma) triggers cellular senescence in human umbilical vascular endothelial cells (HUVECs) via a p53-dependent pathway. This finding suggests IFN-gamma contributes to atherosclerosis pathogenesis through its pro-senescent activity.

Area of Science:

  • Cellular and Molecular Biology
  • Immunology
  • Pathogenesis of Atherosclerosis

Background:

  • Cellular senescence is a state of irreversible cell cycle arrest.
  • Interferons (IFNs) and IFN-inducible genes are altered during replicative senescence in HUVECs.
  • The specific role of IFNs in HUVEC senescence was previously unidentified.

Purpose of the Study:

  • To investigate the role of Interferon-gamma (IFN-gamma) in inducing cellular senescence in Human Umbilical Vascular Endothelial Cells (HUVECs).
  • To elucidate the molecular mechanisms underlying IFN-gamma-induced senescence in HUVECs.
  • To explore the potential contribution of IFN-gamma-induced senescence to atherosclerosis.

Main Methods:

  • Prolonged treatment of HUVECs with IFN-gamma.
  • Assessment of cell cycle arrest (G0/G1), protein levels (p53, p21), SA-beta-gal staining, and DNA damage foci (phospho-H2AX).
  • Experiments using p16-knockdown/null and p53-knockdown/null cells/MEFs, ROS measurement, antioxidant treatment (N-acetylcysteine), and knockdown of ATM kinase or IFI16.

Main Results:

  • IFN-gamma induced cellular senescence in HUVECs, characterized by G0/G1 arrest, increased p53/p21, SA-beta-gal activity, and phospho-H2AX foci.
  • IFN-gamma-induced senescence was dependent on p16 but independent of p53.
  • IFN-gamma increased reactive oxygen species (ROS) production; antioxidants and knockdown of ATM/IFI16 inhibited senescence.

Conclusions:

  • IFN-gamma induces cellular senescence in HUVECs through a p53-dependent DNA damage pathway.
  • The pro-senescent activity of IFN-gamma may contribute to the pathogenesis of atherosclerosis.

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