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Related Concept Videos

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Determining Genome-wide Transcript Decay Rates in Proliferating and Quiescent Human Fibroblasts
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Conserved Senescence Associated Genes and Pathways in Primary Human Fibroblasts Detected by RNA-Seq.

S Marthandan1, M Baumgart1, S Priebe2

  • 1Leibniz-Institute on Aging-Fritz Lipmann Institute e.V. (FLI), Jena, Germany.

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PubMed
Summary

Cellular senescence involves widespread, conserved transcriptome changes across human fibroblast strains. Key pathways like the secretory phenotype are upregulated, while DNA synthesis and cell cycle pathways are downregulated.

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Area of Science:

  • Molecular Biology
  • Genomics
  • Cell Biology

Background:

  • Cellular senescence is a state of irreversible cell cycle arrest.
  • Senescence is linked to aging and age-related diseases.
  • Transcriptomic changes are known to occur during senescence.

Purpose of the Study:

  • To comprehensively map transcriptome and pathway alterations during fibroblast senescence.
  • To identify conserved age-associated gene expression changes across multiple human fibroblast strains.
  • To discover novel senescence-induced pathways.

Main Methods:

  • Deep RNA sequencing of five human fibroblast strains transitioning into senescence.
  • Validation of RNA-sequencing data using real-time PCR.
  • Analysis of cellular protein levels to assess transcriptional regulation.
  • KEGG pathway analysis to identify enriched biological pathways.

Main Results:

  • 78% of age-affected genes showed conserved directional changes across all five fibroblast strains.
  • Confirmed upregulation of the senescence-associated secretory phenotype (SASP).
  • Observed downregulation of DNA synthesis/repair and cell cycle pathways.
  • Identified novel pathway changes: upregulation of endocytotic/phagocytic pathways and downregulation of mRNA metabolism/splicing.

Conclusions:

  • A highly conserved transcriptional program underlies cellular senescence in human fibroblasts.
  • Senescence involves coordinated regulation of gene expression impacting multiple cellular functions.
  • These findings provide a deep understanding of senescence-associated molecular changes and potential therapeutic targets.