The DOI matches its Crossref record; 60 of the 60 references it cites were found in a registry or an index.
Ionizing radiation-induced long-term expression of senescence markers in mice is independent of p53 and immune status
Open accessAbstract
Exposure to IR has been shown to induce the formation of senescence markers, a phenotype that coincides with lifelong delayed repair and regeneration of irradiated tissues. We hypothesized that IR-induced senescence markers could persist long-term in vivo, possibly contributing to the permanent reduction in tissue functionality. Here, we show that mouse tissues exposed to a sublethal dose of IR display persistent (up to 45 weeks, the maximum time analyzed) DNA damage foci and increased p16(INK4a) expression, two hallmarks of cellular senescence and aging. BrdU-labeling experiments revealed that IR-induced damaged cells are preferentially eliminated, at least partially, in a tissue-dependent manner. Unexpectedly, the accumulation of damaged cells was found to occur independent from the DNA damage response modulator p53, and from an intact immune system, as their levels were similar in wild-type and Rag2(-/-) gammaC(-/-) mice, the latter being deficient in T, B, and NK cells. Together, our results provide compelling evidence that exposure to IR induces long-term expression of senescence markers in vivo, an effect that may contribute to the reduced tissue functionality observed in cancer survivors.
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“Ageing and genotoxic stress induce cellular senescence of these stem cells 96,97 and osteoprogenitor cells, 98,99 with subsequent decline in the functions of these cells in both mice and humans.100”
From The costs and benefits of senotherapeutics for human health (2022) · cites this paper as [97]
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Cites
DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139
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Cellular senescence: when bad things happen to good cells
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Self-citationChronic Health Conditions in Adult Survivors of Childhood Cancer
Oeffinger, K. C., Mertens, A. C., Sklar, C. A., Kawashima, T. I., Hudson, M. M., Meadows, A. T., Friedman, D. L., Marina, N. M., Hobbie, W. L., Kadan‐Lottick, N. S., et al. (2006) · New England Journal of Medicine · doi:10.1056/nejmsa060185 · Cited by 3,597
A DNA damage checkpoint response in telomere-initiated senescence
Fagagna, F. D. D., Reaper, P. M., Clay-Farrace, L., Fiegler, H., Carr, P., von Zglinicki, T., Saretzki, G., Carter, N. P., & Jackson, S. P. (2003) · Nature · doi:10.1038/nature02118 · Cited by 2,917 · cited 2×
“…form of cellular senescence is a recognized tumor suppressive response (Collado et al., 2005; Michaloglou et al., 2005; Cosme-Blanco et al., 2007; Feldser & Greider, 2007) that can be induced by p16INK4a expression (Baker et al., 2008) and in many cases DNA damage (d’Adda di Fagagna et al., 2003).”
BackgroundSenescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas
Xue, W., Zender, L., Miething, C., Dickins, R. A., Hernando, E., Krizhanovsky, V., Cordon-Cardo, C., & Lowe, S. W. (2007) · Nature · doi:10.1038/nature05529 · Cited by 2,473
Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion
Rodier, F., Coppé, J.-P., Patil, C. K., Hoeijmakers, W. A. M., Muñoz, D. P., Raza, S. R., Freund, A., Campeau, E., Davalos, A. R., & Campisi, J. (2009) · Nature Cell Biology · doi:10.1038/ncb1909 · Cited by 2,232
Self-citationBRAFE600-associated senescence-like cell cycle arrest of human naevi
Michaloglou, C., Vredeveld, L. C. W., Soengas, M. S., Denoyelle, C., Kuilman, T., van der Horst, C. M. A. M., Majoor, D. M., Shay, J. W., Mooi, W. J., & Peeper, D. S. (2005) · Nature · doi:10.1038/nature03890 · Cited by 2,160
Oncogene-Induced Senescence Relayed by an Interleukin-Dependent Inflammatory Network
Kuilman, T., Michaloglou, C., Vredeveld, L. C. W., Douma, S., van Doorn, R., Desmet, C. J., Aarden, L. A., Mooi, W. J., & Peeper, D. S. (2008) · Cell · doi:10.1016/j.cell.2008.03.039 · Cited by 2,086 · cited 1×
“For example, the senescence-associated secretory phenotype (SASP) has been shown to alter the tissue microenvironment and has been proposed to fuel the development of secondary cancers (Krtolica et al., 2001; Coppe et al., 2006, 2008; Kuilman et al., 2008).”
BackgroundTumor spectrum analysis in p53-mutant mice
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Senescence of Activated Stellate Cells Limits Liver Fibrosis
Krizhanovsky, V., Yon, M., Dickins, R. A., Hearn, S., Simon, J., Miething, C., Yee, H., Zender, L., & Lowe, S. W. (2008) · Cell · doi:10.1016/j.cell.2008.09.015 · Cited by 2,027
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- 10.1016/j.cell.2008.06.049 · DOI · Paper page
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The role of senescent cells in ageing
van Deursen, J. M. (2014) · Nature · doi:10.1038/nature13193 · Cited by 2,623
The Achilles' heel of senescent cells: from transcriptome to senolytic drugs
Zhu, Y., Tchkonia, T., Pirtskhalava, T., Gower, A. C., Ding, H., Giorgadze, N., Palmer, A. K., Ikeno, Y., Hubbard, G. B., Lenburg, M., et al. (2015) · Aging Cell · doi:10.1111/acel.12344 · Cited by 2,584
“By 12 weeks, p16 expression is substantially increased under these conditions (Le et al., 2010).”
BackgroundAn Essential Role for Senescent Cells in Optimal Wound Healing through Secretion of PDGF-AA
Demaria, M., Ohtani, N., Youssef, S. A., Rodier, F., Toussaint, W., Mitchell, J. R., Laberge, R.-M., Vijg, J., Van Steeg, H., Dollé, M. E. T., et al. (2014) · Developmental Cell · doi:10.1016/j.devcel.2014.11.012 · Cited by 2,045
“This IR dose is nonlethal but causes a persistent burden of senescent cells, which are evident 3 months later (Le et al., 2010).”
Self-citationFour faces of cellular senescence
Rodier, F., & Campisi, J. (2011) · Journal of Cell Biology · doi:10.1083/jcb.201009094 · Cited by 2,070
“(c) Senescent cells express a senescence-associated -galactosidase (SA-Bgal; Dimri et al., 1995), which partly reflects the increase in lysosomal mass (Lee et al., 2006).”
Self-citationClearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice
Chang, J., Wang, Y., Shao, L., Laberge, R.-M., Demaria, M., Campisi, J., Janakiraman, K., Sharpless, N. E., Ding, S., Feng, W., et al. (2016) · Nature Medicine · doi:10.1038/nm.4010 · Cited by 1,819
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Metadata
- Authors
- Le, O. N. L., Rodier, F., Fontaine, F., Coppe, J., Campisi, J., DeGregori, J., Laverdière, C., Kokta, V., Haddad, E., & Beauséjour, C. M.
- Affiliations
- Buck Institute for Research on Aging (US)
- University of Colorado Anschutz (US)
- Centre Hospitalier Universitaire Sainte-Justine (CA)
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2010-05-18
- Volume
- 9
- Issue
- 3
- Pages
- 398-409
- ISSN
- 1474-9718 (ISSN-L)
- 1474-9726
- PMC
- PMC2894262
- OpenAlex
- W1489456875
- Cited by
- 168
- References
- 60
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 14 · 2023: 9 · 2022: 9 · 2021: 22 · 2020: 11 · 2019: 14 · 2018: 8 · 2017: 12 · 2016: 7 · 2015: 10 · 2014: 11 · 2013: 10 · 2012: 6
- FWCI
- 5.56
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Aging Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Buck Institute for Research on Aging
- National Institutes of Health
- Canadian Institutes of Health Research (IAO-79317)
- National Institute on Aging (R56AG009909, AG017242, AG-09909, R37AG009909, P30AG025708, AG025708, P01AG017242)
- National Cancer Institute (CA12654, R01CA109657, U24CA126546, CA109657)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- ionizing radiation, cellular senescence, DNA damage foci, p16INK4a, immunodeficiency, Rag2 knockout mice, tissue regeneration, sublethal irradiation, cancer survivors, aging, DNA damage response
- MeSH terms
- Adolescent, Animals, B-Lymphocytes, Child, DNA Damage, Humans, Killer Cells, Natural, Mice, Inbred C57BL, Radiation, Ionizing, T-Lymphocytes, Time Factors, Biomarkers, Tumor Suppressor Protein p53, Cellular Senescence, Cyclin-Dependent Kinase Inhibitor p16, Mice
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