title: Conserved genes and pathways in primary human fibroblast strains undergoing replicative and radiation induced senescence.
abstract: BACKGROUND
  Cellular senescence is induced either internally, for example by replication exhaustion and cell division, or externally, for example by irradiation. In both cases, cellular damages accumulate which, if not successfully repaired, can result in senescence induction. Recently, we determined the transcriptional changes combined with the transition into replicative senescence in primary human fibroblast strains. Here, by γ-irradiation we induced premature cellular senescence in the fibroblast cell strains (HFF and MRC-5) and determined the corresponding transcriptional changes by high-throughput RNA sequencing.
  
  
  RESULTS
  Comparing the transcriptomes, we found a high degree of similarity in differential gene expression in replicative as well as in irradiation induced senescence for both cell strains suggesting, in each cell strain, a common cellular response to error accumulation. On the functional pathway level, "Cell cycle" was the only pathway commonly down-regulated in replicative and irradiation-induced senescence in both fibroblast strains, confirming the tight link between DNA repair and cell cycle regulation. However, "DNA repair" and "replication" pathways were down-regulated more strongly in fibroblasts undergoing replicative exhaustion. We also retrieved genes and pathways in each of the cell strains specific for irradiation induced senescence.
  
  
  CONCLUSIONS
  We found the pathways associated with "DNA repair" and "replication" less stringently regulated in irradiation induced compared to replicative senescence. The strong regulation of these pathways in replicative senescence highlights the importance of replication errors for its induction.
authors.affiliation: Leibniz Institute for Age Research-Fritz Lipmann Institute e.V. (FLI), Beutenbergstrasse 11, 07745, Jena, Germany. smarthandan@fli-leibniz.de.
authors.forename: Shiva
authors.initials: S
authors.lastname: Marthandan
authors.affiliation: Leibniz Institute for Natural Product Research and Infection Biology-Hans-Knöll-Institute e.V. (HKI), Jena, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Menzel
authors.affiliation: Leibniz Institute for Natural Product Research and Infection Biology-Hans-Knöll-Institute e.V. (HKI), Jena, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Priebe
authors.affiliation: Leibniz Institute for Age Research-Fritz Lipmann Institute e.V. (FLI), Beutenbergstrasse 11, 07745, Jena, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Groth
authors.affiliation: Leibniz Institute for Natural Product Research and Infection Biology-Hans-Knöll-Institute e.V. (HKI), Jena, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Guthke
authors.affiliation: Leibniz Institute for Age Research-Fritz Lipmann Institute e.V. (FLI), Beutenbergstrasse 11, 07745, Jena, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Platzer
authors.affiliation: Leibniz Institute for Age Research-Fritz Lipmann Institute e.V. (FLI), Beutenbergstrasse 11, 07745, Jena, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Hemmerich
authors.affiliation: Leibniz Institute for Age Research-Fritz Lipmann Institute e.V. (FLI), Beutenbergstrasse 11, 07745, Jena, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Kaether
authors.affiliation: Leibniz Institute for Age Research-Fritz Lipmann Institute e.V. (FLI), Beutenbergstrasse 11, 07745, Jena, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Diekmann
mesh_terms: D037881:Aborted Fetus; D000704:Analysis of Variance; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000235:genetics / Q000502:physiology* / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair / Q000528:radiation effects; D004261:DNA Replication / Q000528:radiation effects; D015536:Down-Regulation / Q000528:radiation effects; D005347:Fibroblasts / Q000502:physiology / Q000528:radiation effects*; D005720:Gamma Rays; D020869:Gene Expression Profiling; D006801:Humans; D015151:Immunoblotting; D008168:Lung; D008297:Male; D017423:Sequence Analysis, RNA; D013997:Time Factors; D015854:Up-Regulation / Q000528:radiation effects; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D001616:beta-Galactosidase
keywords: Aging; DNA repair; Fibroblasts; Senescence; Transcriptome analysis; γ-irradiation