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Updated: May 8, 2025

Techniques to Induce and Quantify Cellular Senescence
06:51

Techniques to Induce and Quantify Cellular Senescence

Published on: May 1, 2017

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The PARP inhibitor olaparib promotes senescence in murine macrophages

Anna Kieronska-Rudek1, Karim Zuhra1, Kelly Ascenção1

  • 1Section of Pharmacology, Department of Oncology, Microbiology and Immunology, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland.

Geroscience
|May 6, 2025
PubMed

Insights

Olaparib, a PARP inhibitor, worsens cellular senescence by increasing DNA damage and cell death markers. Senescent cells show heightened sensitivity to olaparib, impacting mitochondrial function and bioenergetics.

Area of Science:

  • Cellular and Molecular Biology
  • Aging Research
  • Cancer Therapeutics

Background:

  • Cellular senescence, characterized by cell cycle arrest and DNA damage, is linked to aging and cancer.
  • Poly (ADP-ribose) polymerase (PARP) inhibitors like olaparib are used in cancer therapy.
  • The impact of PARP inhibitors on senescent cells remains largely unexplored.

Purpose of the Study:

  • To investigate the effects of olaparib on non-senescent and senescent murine macrophages.
  • To determine if olaparib influences senescence markers and DNA damage repair pathways.
  • To assess olaparib's cytotoxicity and impact on cellular bioenergetics in senescent cells.

Main Methods:

  • Comparison of senescent and non-senescent RAW 264.7 murine macrophages.
  • Treatment with olaparib at various concentrations.
  • Assessment of senescence markers (SA-β-gal, p21), DNA damage, proliferation, cytotoxicity (apoptosis, necrosis), mitochondrial activity, and cellular bioenergetics.

Main Results:

  • Senescent cells displayed higher baseline PARP1, PARylation, and DNA damage.
  • Olaparib amplified senescence markers, exacerbated DNA damage, and inhibited proliferation, particularly in senescent cells.
  • Olaparib induced cytotoxicity via apoptosis and necrosis, with senescent cells showing more necrosis. Mitochondrial activity and bioenergetics were impaired more severely in senescent cells.

Conclusions:

  • Olaparib exhibits enhanced cytotoxic and pro-senescent effects in senescent immune cells.
  • Senescent cells are more vulnerable to olaparib-induced DNA damage and bioenergetic impairment.
  • Findings suggest implications for olaparib use in elderly cancer patients with a higher senescent cell burden.
Keywords:
AgingMacrophagesOlaparibPARPsSenescence

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