Journal Article

Conserved Senescence Associated Genes and Pathways in Primary Human Fibroblasts Detected by RNA-Seq

Hemmerich, P., Guthke, R., Marthandan, S., Baumgart, M., Kaether, C., Groth, M., Platzer, M., Diekmann, S., Priebe, S., Cellerino, A., Schaer, J.

2016

Overview

Cellular senescence correlates with changes in the transcriptome. To obtain a complete view on senescence-associated transcription networks and pathways, we assessed by deep RNA sequencing the transcriptomes of five of the most commonly used laboratory strains of human fibroblasts during their transition into senescence. In a number of cases, we verified the RNA-seq data by real-time PCR. By determining cellular protein levels we observed that the age-related expression of most but not all genes is regulated at the transcriptional level. We found that 78% of the age-affected differentially expressed genes were commonly regulated in the same direction (either up- or down-regulated) in all five fibroblast strains, indicating a strong conservation of age-associated changes in the transcriptome. KEGG pathway analyses confirmed up-regulation of the senescence-associated secretory phenotype and down-regulation of DNA synthesis/repair and most cell cycle pathways common in all five cell strains. Newly identified senescence-induced pathways include up-regulation of endocytotic/phagocytic pathways and down-regulation of the mRNA metabolism and the mRNA splicing pathways. Our results provide an unprecedented comprehensive and deep view into the individual and common transcriptome and pathway changes during the transition into of senescence of five human fibroblast cell strains.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Age / Aging / Biology / Biology and Life Sciences / Cell aging / Cell cycle / Cell Proliferation / Cellular Senescence - genetics / Conservation / Conserved Sequence / Deoxyribonucleic acid / DNA / DNA biosynthesis / DNA damage / DNA repair / Female / Fibroblasts / Fibroblasts - cytology / Fibroblasts - metabolism / Gene expression / Gene Expression Profiling / Gene sequencing / Genes / Genetic aspects / Humans / Infections / Kinases / Laboratories / Lipmann, Fritz / Male / Medicine and Health Sciences / Metabolism / Natural products / Neurosciences / Phagocytes / Physiological aspects / Pregnancy / Proteins / Research and Analysis Methods / Ribonucleic acid / RNA / RNA sequencing / RNA, Messenger - genetics / RNA, Messenger - metabolism / Rodents / Senescence / Sequence Analysis, RNA / Splicing / Transcription / Transcription factors