Acute systemic DNA damage in youth does not impair immune defense with aging
AuthorPugh, Jason L.
Foster, Sarah A.
Sukhina, Alona S.
Uhrlaub, Jennifer L.
Smithey, Megan J.
AffiliationUniv Arizona, Coll Med, Dept Immunobiol
Univ Arizona, Coll Med, Arizona Ctr Aging
Univ Arizona, Grad Interdisciplinary Program Genet
Univ Arizona, Inst BIO5
Univ Arizona, Coll Med, Translat Neurotrauma Res Program, Barrow Neurol Inst,Phoenix Childrens Hosp,Dept Ch
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CitationAcute systemic DNA damage in youth does not impair immune defense with aging 2016, 15 (4):686 Aging Cell
Rights© 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License
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AbstractAging-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.
VersionFinal published version
SponsorsUSPHS contract from the National Institute of Allergy and Infectious Diseases [HHSN272200900059C]