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Induction and Validation of Cellular Senescence in Primary Human Cells
08:18

Induction and Validation of Cellular Senescence in Primary Human Cells

Published on: June 20, 2018

Senescing human cells and ageing mice accumulate DNA lesions with unrepairable double-strand breaks

Olga A Sedelnikova1, Izumi Horikawa, Drazen B Zimonjic

  • 1Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.

Nature Cell Biology
|February 3, 2004
PubMed

Insights

Cellular senescence in humans and animals involves accumulating DNA double-strand breaks (DSBs), visualized as gamma-H2AX foci. These unrepaired DNA lesions may drive the aging process in mammals.

Area of Science:

  • Cellular biology
  • Gerontology
  • Molecular genetics

Background:

  • Cellular senescence is a hallmark of aging in humans and animals.
  • The precise relationship between cellular senescence and organismal aging remains unclear.
  • DNA damage is implicated in cellular senescence and aging.

Purpose of the Study:

  • To investigate the accumulation of DNA double-strand breaks (DSBs) during cellular senescence.
  • To explore the potential role of DSBs in mammalian aging.

Main Methods:

  • Utilized gamma-H2AX foci as markers for DSBs in human cell cultures and aging mice.
  • Examined the colocalization of gamma-H2AX foci with DNA repair factors and telomeres.
  • Assessed the persistence of gamma-H2AX foci after repair of radiation-induced DSBs.

Main Results:

  • Gamma-H2AX foci accumulate in senescing human cells and aging mice.
  • These foci colocalize with DNA repair factors but not significantly with telomeres.
  • A subset of gamma-H2AX foci, termed cryptogenic gamma-foci, persist after repair of induced DSBs.

Conclusions:

  • Accumulation of unrepaired DSBs, indicated by persistent gamma-H2AX foci, is a feature of cellular senescence.
  • These unrepaired DSBs may play a causal role in the aging process of mammals.

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