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Updated: Nov 14, 2025

Techniques to Induce and Quantify Cellular Senescence
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CTCF Mediates Replicative Senescence Through POLD1

Yuli Hou1, Qiao Song1, Shichao Gao1

  • 1Clinical Laboratory of Xuanwu Hospital, Capital Medical University, Beijing, China.

Frontiers in Cell and Developmental Biology
|March 11, 2021
PubMed

Insights

The CCCTC-binding factor (CTCF) regulates DNA polymerase δ subunit 1 (POLD1) expression. Age-related decreases in CTCF downregulate POLD1, accelerating cellular aging.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cellular Biology

Background:

  • DNA polymerase δ subunit 1 (POLD1) is crucial for DNA synthesis and repair.
  • POLD1 expression decreases with age, contributing to replicative senescence.
  • The mechanisms behind age-related POLD1 downregulation are not fully understood.

Purpose of the Study:

  • To elucidate the transcriptional regulation of POLD1 in aging.
  • To investigate the role of the CCCTC-binding factor (CTCF) in POLD1 expression during aging.

Main Methods:

  • Analysis of CTCF binding to the POLD1 promoter.
  • Experimental manipulation of CTCF and POLD1 levels using shRNA and overexpression vectors.
  • Assessment of cellular senescence markers post-transfection.

Main Results:

  • CTCF binds to two sites within the POLD1 promoter region.
  • CTCF binding to the POLD1 promoter is positively correlated with CTCF levels and aging.
  • Reduced CTCF levels lead to decreased POLD1 expression and increased cellular senescence characteristics.

Conclusions:

  • CTCF binding to the POLD1 promoter is a key regulatory mechanism for POLD1 expression in aging.
  • Age-related decline in CTCF levels results in POLD1 downregulation.
  • This CTCF-mediated decrease in POLD1 transcription accelerates cellular aging.
Keywords:
CTCFPOLD1agingtranscription factortranscriptional regulation

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