Acute systemic DNA damage in youth does not impair immune defense with aging
| Autor: | Megan J. Smithey, Janko Nikolich-Žugich, Sarah A. Foster, Jennifer L. Uhrlaub, Janka Petravic, Kei Nakachi, Jason L. Pugh, Alona S. Sukhina, Jose L. Padilla-Torres, Tomonori Hayashi |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Immune defense Male Allergy Aging West Nile virus DNA damage T-Lymphocytes Whole body irradiation T‐cell Biology medicine.disease_cause 03 medical and health sciences 0302 clinical medicine Immunity Risk Factors medicine Animals Homeostasis West Nile Virus Vaccines irradiation T-cell aging vaccination Vaccination Dose-Response Relationship Radiation Cell Biology Original Articles medicine.disease Survival Analysis Mice Inbred C57BL 030104 developmental biology 030220 oncology & carcinogenesis Immunology Original Article Immunologic memory Immunologic Memory West Nile Fever Whole-Body Irradiation |
| Zdroj: | Aging Cell |
| ISSN: | 1474-9718 |
| DOI: | 10.1111/acel.12478 |
| Popis: | Summary Aging‐related decline in immunity is believed to be the main driver behind decreased vaccine efficacy and reduced resistance to infections in older adults. Unrepaired DNA damage is known to precipitate cellular senescence, which was hypothesized to be the underlying cause of certain age‐related phenotypes. Consistent with this, some hallmarks of immune aging were more prevalent in individuals exposed to whole‐body irradiation (WBI), which leaves no anatomical repository of undamaged hematopoietic cells. To decisively test whether and to what extent WBI in youth will leave a mark on the immune system as it ages, we exposed young male C57BL/6 mice to sublethal WBI (0.5–4 Gy), mimicking human survivor exposure during nuclear catastrophe. We followed lymphocyte homeostasis thorough the lifespan, response to vaccination, and ability to resist lethal viral challenge in the old age. None of the irradiated groups showed significant differences compared with mock‐irradiated (0 Gy) animals for the parameters measured. Even the mice that received the highest dose of sublethal WBI in youth (4 Gy) exhibited equilibrated lymphocyte homeostasis, robust T‐ and B‐cell responses to live attenuated West Nile virus (WNV) vaccine and full survival following vaccination upon lethal WNV challenge. Therefore, a single dose of nonlethal WBI in youth, resulting in widespread DNA damage and repopulation stress in hematopoietic cells, leaves no significant trace of increased immune aging in a lethal vaccine challenge model. |
| Databáze: | OpenAIRE |
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