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Updated: Jul 11, 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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Androgen signaling stabilizes genomes to counteract senescence by promoting XRCC4 transcription

Yu Chen1,2, Zhengyi Zhen1,2, Lingjiang Chen1,2

  • 1Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.

EMBO Reports
|November 13, 2023
PubMed

Insights

Aging reduces DNA repair by decreasing XRCC4 expression. Androgen receptor (AR) signaling, boosted by dihydrotestosterone (DHT), restores XRCC4, stabilizing the genome and reversing aging signs.

Area of Science:

  • Molecular Biology
  • Genetics
  • Gerontology

Background:

  • Aging is linked to reduced DNA repair capacity, impacting tissue function.
  • Hormonal changes during aging affect reproductive organs, but impact on non-reproductive tissue DNA repair is unclear.

Purpose of the Study:

  • To investigate the impact of aging on DNA repair mechanisms in non-reproductive tissues.
  • To explore the role of androgen receptor (AR) signaling in regulating DNA repair factor XRCC4 expression during aging.

Main Methods:

  • Analysis of XRCC4 expression in skin fibroblasts from donors across a wide age range.
  • Investigating the transcriptional regulation of XRCC4 by the androgen receptor (AR).
  • Utilizing dihydrotestosterone (DHT) to assess its effect on XRCC4 expression and cellular aging models.

Main Results:

  • XRCC4 expression, crucial for DNA double-strand break repair, decreases with age via transcriptional downregulation.
  • AR directly binds to and enhances the XRCC4 promoter, promoting its transcription.
  • DHT treatment restores XRCC4 expression and genome stability in cellular aging models.
  • DHT reverses senescence-associated phenotypes.

Conclusions:

  • Androgen receptor signaling is critical for maintaining DNA repair capacity during aging.
  • DHT can restore DNA repair function and counteract aging phenotypes, suggesting therapeutic potential.
Keywords:
DNA repairXRCC4agingandrogen receptordihydrotestosterone

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