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Telomere Length and Telomerase Activity; A Yin and Yang of Cell Senescence
12:08

Telomere Length and Telomerase Activity; A Yin and Yang of Cell Senescence

Published on: May 22, 2013

Telomerase-dependent reactivation of DNA synthesis in macrophages implies alteration of telomeres

Y E Yegorov1, E V Kazimirchuk, S M Terekhov

  • 1Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 32 Vavilov str. Moscow, 119991, Russia. yegorov@genome.eimb.relarn.ru

Cell Biology International
|December 7, 2002
PubMed

Insights

Telomerase activity, introduced via the hTERT gene, enables macrophage nucleus reactivation in cell fusion studies. Inhibiting telomerase blocks this reactivation, suggesting telomere damage in macrophage nuclei.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • Limited lifespan cells cannot reactivate DNA synthesis in macrophage nuclei within heterokaryons.
  • The role of telomerase in macrophage nucleus reactivation remained unclear.

Purpose of the Study:

  • To investigate the role of telomerase in macrophage nucleus reactivation.
  • To determine if introducing telomerase activity can restore DNA synthesis in macrophage nuclei.

Main Methods:

  • Formation of heterokaryons between macrophages and immortal fibroblasts (3T3 Swiss or hTERT-engineered human fibroblasts).
  • Assay of telomerase activity using reverse transcriptase inhibitors and anti-sense oligonucleotides.
  • Monitoring DNA synthesis in macrophage and fibroblast nuclei within heterokaryons.

Main Results:

  • Introduction of the hTERT gene into human fibroblasts conferred telomerase activity and induced macrophage nucleus reactivation.
  • Telomerase inhibition blocked DNA synthesis reactivation in macrophage nuclei but not in fibroblast nuclei.
  • These findings suggest telomere shortening or damage in macrophage nuclei.

Conclusions:

  • Telomerase activity is crucial for reactivating DNA synthesis in macrophage nuclei within heterokaryons.
  • Macrophage nuclei may possess shortened or damaged telomeres.
  • Heterokaryons involving macrophages serve as a model for studying telomerase inhibitors.

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