Conserved genes and pathways in primary human fibroblast strains undergoing replicative and radiation induced senescence
Open accessAbstract
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. CONCLUSION: 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.
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These processes (DNA repair and cell cycle) are commonly damaged in primary human fibroblast strains undergoing a cellular aging process as a consequence of finite proliferative capacity or oxidative stress.
“These processes are commonly damaged in primary human fibroblast strains undergoing a cellular aging process as a consequence of finite proliferative capacity or oxidative stress [67]”
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WI-38 senescence is associated with global and site-specific hypomethylation
Sidler, C. L., Wóycicki, R. K., Kovalchuk, I., & Kovalchuk, O. (2014) · Aging · doi:10.18632/aging.100679 · Cited by 24 · see citing works
Chronic kidney disease in older people with intellectual disability: Results of the HA-ID study
de Winter, C. F., Echteld, M. A., & Evenhuis, H. M. (2013) · Research in Developmental Disabilities · doi:10.1016/j.ridd.2013.11.005 · Cited by 23 · see citing works
HLA-A and HLA-B transcription decrease with ageing in peripheral blood leucocytes
Morvan, C. L., Cogné, M., & Drouet, M. (2001) · Clinical & Experimental Immunology · doi:10.1046/j.1365-2249.2001.01610.x · Cited by 23 · see citing works
Heat-Induced Proteasomic Degradation of HSF1 in Serum-Starved Human Fibroblasts Aging in Vitro
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Age-Dependent Changes in DNA Repair in Radiation-Exposed Mice
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Carey, J. P. W., Knowell, A. E., Chinaranagari, S., & Chaudhary, J. (2013) · PubMed · Cited by 20 · see citing works
Cleavage of MCM2 licensing protein fosters senescence in human keratinocytes
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Comparative Meta-Analysis of Transcriptomics Data during Cellular Senescence andIn VivoTissue Ageing
Voutetakis, K., Chatziioannou, A. A., Gonos, E. S., & Trougakos, I. P. (2015) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2015/732914 · Cited by 17 · see citing works
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Age-related changes in the induction of DNA polymerases in rat liver by γ-ray irradiation
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Flagged first, then by citations
1 of the 210 references couldn’t be matched to a known paper.
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Skin Aging, Cellular Senescence and Natural Polyphenols
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Gene expression hallmarks of cellular ageing
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DePianto, D. J., Heiden, J. A. V., Morshead, K. B., Sun, K.-H., Modrusan, Z. D., Teng, G., Wolters, P. J., & Arron, J. R. (2021) · JCI Insight · doi:10.1172/jci.insight.143626 · Cited by 93 · see citing works
Short-term gain, long-term pain: the senescence life cycle and cancer
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Radiation-induced liver injury and hepatocyte senescence
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Induction and Validation of Cellular Senescence in Primary Human Cells
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Titration of RAS alters senescent state and influences tumour initiation
Chan, A. S. L., Zhu, H., Narita, M., Cassidy, L. D., Young, A. R. J., Bermejo‐Rodríguez, C., Janowska, A. T., Chen, H., Gough, S., Oshimori, N., et al. (2024) · Nature · doi:10.1038/s41586-024-07797-z · Cited by 34 · see citing works
Brief guide to senescence assays using cultured mammalian cells
Kang, E. S., Kang, C., Lee, Y., & Lee, S. (2024) · Molecules and Cells · doi:10.1016/j.mocell.2024.100102 · Cited by 30 · see citing works
Kaistha, A., Oc, S., Garrido, A. M., Taylor, J. C. K., Imaz, M., Worssam, M. D., Uryga, A., Grootaert, M. O. J., Foote, K., Finigan, A. J., et al. (2025) · Cardiovascular Research · doi:10.1093/cvr/cvaf102 · Cited by 28 · see citing works
Babayan, N., Grigoryan, B. A., Khondkaryan, L., Tadevosyan, G., Sarkisyan, N., Grigoryan, R., Apresyan, L., Aroutiounian, R. M., Vorobyeva, N. Y., Pustovalova, M. V., et al. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20205140 · Cited by 26 · see citing works
Psaroudis, R. T., Singh, U., Lora, M., Jeon, P., Boursiquot, A., Stochaj, U., Langlais, D., & Colmegna, I. (2022) · Stem Cell Research & Therapy · doi:10.1186/s13287-022-03026-4 · Cited by 22 · see citing works
Tu, M., Wei, T., Jia, Y., Wang, Y., & Wu, J. (2022) · Journal of Thoracic Disease · doi:10.21037/jtd-22-886 · Cited by 22 · see citing works
Replicative and radiation-induced aging: a comparison of gene expression profiles
Aliper, A. M., Bozdaganyan, M. E., Orekhov, P. S., Zhavoronkov, A. A., & Osipov, A. N. (2019) · Aging · doi:10.18632/aging.101921 · Cited by 22 · see citing works
Sha, J., Arbesman, J., & Harter, M. L. (2020) · Pigment Cell & Melanoma Research · doi:10.1111/pcmr.12888 · Cited by 19 · see citing works
AAontology: An Ontology of Amino Acid Scales for Interpretable Machine Learning
Breimann, S., Kamp, F., Steiner, H., & Frishman, D. (2024) · Journal of Molecular Biology · doi:10.1016/j.jmb.2024.168717 · Cited by 15 · see citing works
Isolation and Culture of Primary Fibroblasts from Neonatal Murine Hearts to Study Cardiac Fibrosis
Kumar, S. A., Nagesh, D., Ramasubbu, V., Prabhashankar, A. B., & Sundaresan, N. R. (2023) · BIO-PROTOCOL · doi:10.21769/bioprotoc.4616 · Cited by 14 · see citing works
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Microphase separation produces interfacial environment within diblock biomolecular condensates
Latham, A. P., Zhu, L., Sharon, D. A., Ye, S., Willard, A. P., Zhang, X., & Zhang, B. (2025) · eLife · doi:10.7554/elife.90750.4 · Cited by 11 · see citing works
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Systematic transcriptomic analysis and temporal modelling of human fibroblast senescence
Scanlan, R.-L., Pease, L., O’Keefe, H., Guimera, A. M., Rasmussen, L. J., Wordsworth, J., & Shanley, D. P. (2024) · Frontiers in Aging · doi:10.3389/fragi.2024.1448543 · Cited by 11 · see citing works
Targeted Therapeutics Delivery by Exploiting Biophysical Properties of Senescent Cells
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Systematic transcriptomic analysis and temporal modelling of the senescent human fibroblastPreprint
Scanlan, R.-L., Pease, L., O’Keefe, H., Guimera, A. M., Shanley, D., & Wordsworth, J. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.08.16.504144 · Cited by 1 · see citing works
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Psaroudis, R. T., Singh, U., Lora, M., Jeon, P., Boursiquot, A., Stochaj, U., Langlais, D., & Colmegna, I. (2022) · Figshare · doi:10.6084/m9.figshare.20381979
A Stickiness Scale for Disordered Proteins
Cao, F., Tesei, G., & Lindorff‐Larsen, K. (2026) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.6c00592
- Authors
- Marthandan, S., Menzel, U., Priebe, S., Groth, M., Guthke, R., Platzer, M., Hemmerich, P., Kaether, C., & Diekmann, S.
- Affiliations
- Leibniz Institute on Aging - Fritz Lipmann Institute (FLI) (DE)
- Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie e. V. - Hans-Knöll-Institut (HKI) (DE)
- Corresponding author
- Marthandan, Shiva
- Venue
- Biological Research
- Published
- 2016-07-28
- Volume
- 49
- Issue
- 1
- Pages
- 34-34
- ISSN
- 0716-9760 (ISSN-L)
- 0717-6287
- PMC
- PMC4963952
- OpenAlex
- W2491783232
- Cited by
- 39
- References
- 210
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 6 · 2023: 3 · 2022: 7 · 2021: 5 · 2020: 2 · 2019: 6 · 2018: 5 · 2017: 2
- FWCI
- 3.49
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Biological Research (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (publishedVersion, other-oa)
- Americanae (AECID Library) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Informationszentrum Lebenswissenschaften (ZB MED) (submittedVersion, cc-by)
- Funders
- Bundesministerium für Bildung und Forschung– BMBF (0315581)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Dermatology › Skin Protection and Aging
- Keywords
- cellular senescence, replicative senescence, radiation-induced senescence, gamma irradiation, primary human fibroblasts, DNA repair, DNA replication, cell cycle regulation, transcriptome, differential gene expression, DNA damage accumulation, MRC-5 cells
- MeSH terms
- Analysis of Variance, beta-Galactosidase, Cells, Cultured, DNA Damage, DNA Repair, DNA Replication, Fibroblasts, Gamma Rays, Humans, Lung, Male, Time Factors, Immunoblotting, Down-Regulation, Up-Regulation, Cellular Senescence, Sequence Analysis, RNA, Gene Expression Profiling, Aborted Fetus
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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