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    Acute systemic DNA damage in youth does not impair immune defense with aging

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    Pugh_et_al-2016-Aging_Cell.pdf
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    Author
    Pugh, Jason L.
    Foster, Sarah A.
    Sukhina, Alona S.
    Petravic, Janka
    Uhrlaub, Jennifer L.
    Padilla-Torres, Jose
    Hayashi, Tomonori
    Nakachi, Kei
    Smithey, Megan J.
    Nikolich-Žugich, Janko
    Affiliation
    Univ 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
    Issue Date
    2016-08
    Keywords
    aging
    DNA damage
    irradiation
    T-cell
    vaccination
    
    Metadata
    Show full item record
    Publisher
    WILEY-BLACKWELL
    Citation
    Acute systemic DNA damage in youth does not impair immune defense with aging 2016, 15 (4):686 Aging Cell
    Journal
    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
    Collection Information
    This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.
    Abstract
    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.
    ISSN
    14749718
    PubMed ID
    27072188
    DOI
    10.1111/acel.12478
    Version
    Final published version
    Sponsors
    USPHS contract from the National Institute of Allergy and Infectious Diseases [HHSN272200900059C]
    Additional Links
    http://doi.wiley.com/10.1111/acel.12478
    ae974a485f413a2113503eed53cd6c53
    10.1111/acel.12478
    Scopus Count
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    UA Faculty Publications

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