Restored immune cell functions upon clearance of senescence in the irradiated splenic environment
Open accessAbstract
Some studies show eliminating senescent cells rejuvenate aged mice and attenuate deleterious effects of chemotherapy. Nevertheless, it remains unclear whether senescence affects immune cell function. We provide evidence that exposure of mice to ionizing radiation (IR) promotes the senescent‐associated secretory phenotype (SASP) and expression of p16 INK4a in splenic cell populations. We observe splenic T cells exhibit a reduced proliferative response when cultured with allogenic cells in vitro and following viral infection in vivo. Using p16‐3MR mice that allow elimination of p16 INK4a ‐positive cells with exposure to ganciclovir, we show that impaired T‐cell proliferation is partially reversed, mechanistically dependent on p16 INK4a expression and the SASP. Moreover, we found macrophages isolated from irradiated spleens to have a reduced phagocytosis activity in vitro, a defect also restored by the elimination of p16 INK4a expression. Our results provide molecular insight on how senescence‐inducing IR promotes loss of immune cell fitness, which suggest senolytic drugs may improve immune cell function in aged and patients undergoing cancer treatment.
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Chronic exposure to cell stressors can induce premature senescence in the young.
“Chronic exposure to cell stressors can also induce premature senescence in the young [15].”
From Oral Microbially-Induced Small Extracellular Vesicles Cross the Blood–Brain Barrier (2024) · cites this paper as [15]
The Introduction says senescent cells can appear after exposure to DNA-damaging agents, and the Results report senescence-associated changes after irradiation of young mice. However, the Methods specify a single radiation dose, not chronic exposure; the paper therefore does not establish the claim's chronic-exposure qualifier. (LLM, conf=0.86)
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- Authors
- Palacio, L., Goyer, M., Maggiorani, D., Espinosa, A., Villeneuve, N., Bourbonnais, S., Moquin‐Beaudry, G., Le, O., Demaria, M., Davalos, A. R., Decaluwe, H., & Beauséjour, C.
- Affiliations
- Centre Hospitalier Universitaire Sainte-Justine (CA)
- Centre de recherche du CHU Ste‐Justine Montreal Quebec Canada
- University Medical Center Groningen (NL)
- Buck Institute for Research on Aging (US)
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2019-05-31
- Volume
- 18
- Issue
- 4
- Pages
- e12971-e12971
- ISSN
- 1474-9718 (ISSN-L)
- 1474-9726
- PMC
- PMC6612633
- OpenAlex
- W2947406234
- Cited by
- 54
- References
- 41
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 12 · 2023: 9 · 2022: 6 · 2021: 9 · 2020: 10 · 2019: 1
- FWCI
- 4.46
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Aging Cell (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, cc-by)
- Funders
- Canadian Institutes of Health Research (MOP-341566, MOP-130469)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- cellular senescence, senolytics, ionizing radiation, senescence-associated secretory phenotype, p16INK4a, splenic T cells, T cell proliferation, macrophage phagocytosis, ganciclovir, immunosenescence, chemotherapy-induced immunosuppression, spleen
- MeSH terms
- Animals, Antiviral Agents, Arenaviridae Infections, Cells, Cultured, Lymphocytic choriomeningitis virus, Macrophages, Mice, Transgenic, Phenotype, Radiation, Ionizing, Rejuvenation, Spleen, T-Lymphocytes, Ganciclovir, Cellular Senescence, Cyclin-Dependent Kinase Inhibitor p16, Cell Proliferation, Mice
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