title: Acute systemic DNA damage in youth does not impair immune defense with aging.
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.
authors.affiliation: Department of Immunobiology, University of Arizona College of Medicine, Tucson, AZ, USA.|Arizona Center on Aging, University of Arizona College of Medicine, Tucson, AZ, USA.|Graduate Interdisciplinary Program in Genetics, University of Arizona, Tucson, AZ, USA.
authors.forename: Jason L
authors.initials: JL
authors.lastname: Pugh
authors.affiliation: Department of Immunobiology, University of Arizona College of Medicine, Tucson, AZ, USA.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Foster
authors.affiliation: Department of Immunobiology, University of Arizona College of Medicine, Tucson, AZ, USA.
authors.forename: Alona S
authors.initials: AS
authors.lastname: Sukhina
authors.affiliation: Centre for Vascular Research, University of New South Wales, Sydney, NSW , 2052, Australia.
authors.forename: Janka
authors.initials: J
authors.lastname: Petravic
authors.affiliation: Department of Immunobiology, University of Arizona College of Medicine, Tucson, AZ, USA.|Arizona Center on Aging, University of Arizona College of Medicine, Tucson, AZ, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Uhrlaub
authors.affiliation: Department of Immunobiology, University of Arizona College of Medicine, Tucson, AZ, USA.
authors.forename: Jose
authors.initials: J
authors.lastname: Padilla-Torres
authors.affiliation: Radiation Effects Research Foundation, Minato-Ku, Hiroshima, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Hayashi
authors.affiliation: Radiation Effects Research Foundation, Minato-Ku, Hiroshima, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Nakachi
authors.affiliation: Department of Immunobiology, University of Arizona College of Medicine, Tucson, AZ, USA.|Arizona Center on Aging, University of Arizona College of Medicine, Tucson, AZ, USA.
authors.forename: Megan J
authors.initials: MJ
authors.lastname: Smithey
authors.affiliation: Department of Immunobiology, University of Arizona College of Medicine, Tucson, AZ, USA.|Arizona Center on Aging, University of Arizona College of Medicine, Tucson, AZ, USA.|Graduate Interdisciplinary Program in Genetics, University of Arizona, Tucson, AZ, USA.|The BIO5 Institute, University of Arizona, Tucson, AZ, USA.
authors.forename: Janko
authors.initials: J
authors.lastname: Nikolich-Žugich
mesh_terms: D000375:Aging / Q000276:immunology*; D000818:Animals; D004249:DNA Damage; D004307:Dose-Response Relationship, Radiation; D006706:Homeostasis; D007109:Immunity; D007156:Immunologic Memory; D008297:Male; D008810:Mice, Inbred C57BL; D012307:Risk Factors; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000378:metabolism; D014611:Vaccination; D014901:West Nile Fever / Q000276:immunology / Q000821:virology; D053060:West Nile Virus Vaccines / Q000276:immunology; D014902:West Nile virus / Q000502:physiology; D014916:Whole-Body Irradiation
chemical_list: D053060:West Nile Virus Vaccines
keywords: DNA damage; T-cell; aging; irradiation; vaccination