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

Jason L. Pugh, Sarah A. Foster, Alona S. Sukhina, Janka Petravic, Jennifer L. Uhrlaub, Jose Padilla-Torres, Tomonori Hayashi, Kei Nakachi, Megan J. Smithey, Janko Nikolich-Žugich

Research output: Contribution to journalArticle

5 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)686-693
Number of pages8
JournalAging Cell
Volume15
Issue number4
DOIs
StatePublished - Aug 1 2016

Keywords

  • DNA damage
  • T-cell
  • aging
  • irradiation
  • vaccination

ASJC Scopus subject areas

  • Aging
  • Cell Biology

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  • Cite this

    Pugh, J. L., Foster, S. A., Sukhina, A. S., Petravic, J., Uhrlaub, J. L., Padilla-Torres, J., Hayashi, T., Nakachi, K., Smithey, M. J., & Nikolich-Žugich, J. (2016). Acute systemic DNA damage in youth does not impair immune defense with aging. Aging Cell, 15(4), 686-693. https://doi.org/10.1111/acel.12478