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Elevated Senescence Markers in Developing Trisomy 21 Human Lungs

  • 0The Lundquist Institute, Pediatrics, Torrance, California, United States.
American Journal of Respiratory Cell and Molecular Biology +

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February 28, 2025

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February 28, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Human trisomies, including Down syndrome (T21), are linked to cellular senescence and DNA damage in fetal lung development. This study reveals increased senescence markers and oxidative stress, particularly in T21 lungs.

Area Of Science

  • Genetics
  • Developmental Biology
  • Cellular Biology

Background

  • Human chromosomal anomalies, such as trisomies, significantly impact gene expression and lead to various cellular and organ phenotypes.
  • Increased cellular senescence (SEN) and oxidative stress are emerging concerns in trisomic conditions.

Purpose Of The Study

  • To investigate cellular senescence, senescence-associated secretory phenotype (SASP), and oxidative stress in human fetal lung tissues and fibroblasts with trisomy 13, 18, and 21.
  • To establish the relationship between trisomy and these cellular stress markers during prenatal lung development.

Main Methods

  • Analysis of human fetal lung tissues and primary fibroblasts from trisomy 13, 18, and 21.
  • Telomerase associated foci (TAF) staining for DNA damage.
  • RT-qPCR for SEN and SASP marker gene expression (CDKN2B, IL-6, CXCL8, CDKN2A).
  • γ-H2AX staining for DNA damage.
  • Assessment of reactive oxygen species (ROS) using MitoSOX and CellROX.

Main Results

  • DNA damage (TAF, γ-H2AX) was observed in T21 and T18 lungs, with γ-H2AX upregulated across all trisomies, especially T21.
  • Trisomy 21 (T21) and T18 lungs showed increased SEN marker CDKN2B and SASP markers IL-6 and CXCL8.
  • Trisomy 13 (T13) lungs exhibited CDKN2A upregulation without significant SASP changes.
  • T21 fibroblasts showed elevated SEN markers, P21 expression, and increased ROS levels.
  • Fibroblasts from T13 and T18 also showed increased γ-H2AX positive cells.

Conclusions

  • This study presents the first evidence linking cellular senescence and trisomy anomalies during prenatal human lung development.
  • Trisomy 21 demonstrates a significant association with elevated senescence markers, DNA damage, and oxidative stress in developing lung tissue.
  • The findings highlight potential cellular mechanisms underlying the phenotypic consequences of trisomies in lung development.

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