Long term effects of radiation exposure on telomere lengths of leukocytes and its associated biomarkers among atomic-bomb survivors.
Ionizing radiation (IR) is a major source of cellular damage and the immediate cellular response to IR has been well characterized. But the long-term impact of IR on cell function and its relationship with aging are not known. Here, we examined the IR effects on telomere length and other biomarkers 50 to 68 years post-exposure (two time points per person) in survivors of the atomic bombing at Hiroshima during WWII. We found that telomere length of leukocytes was inversely correlated with the dose of IR (p=0.008), and this effect was primarily found in survivors who were exposed at younger ages; specifically those <12 years old (p=0.0004). Although a dose-related retardation of telomere shortening with age was observed in the cross-sectional data, longitudinal follow-up after 11 years did not show IR exposure-related alteration of the rate of telomere shortening with age. In addition, IR diminished the associations between telomere length and selected aging biomarkers that were observed in survivors with no dose. These included uric acid metabolism, cytokines, and blood T cell counts. These findings showed long-lasting detrimental effects of IR on telomere length of leukocytes in both dose- and age-at-exposure dependent manner, and on alterations of biomarkers with aging.
Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.
Ana
A
Lustig
Duke University, Durham, North Carolina, USA.
Ivo
I
Shterev
Health Informatics Institute, University of South Florida, Tampa, Florida, USA.
Susan
S
Geyer
Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.
Alvin
A
Shi
Department of Radiobiology/Molecular Epidemiology, Radiation Effects Research Foundation (RERF), Hiroshima, Japan.
Yiqun
Y
Hu
Department of Radiobiology/Molecular Epidemiology, Radiation Effects Research Foundation (RERF), Hiroshima, Japan.
Yukari
Y
Morishita
Department of Radiobiology/Molecular Epidemiology, Radiation Effects Research Foundation (RERF), Hiroshima, Japan.
Hiroko
H
Nagamura
Department of Radiobiology/Molecular Epidemiology, Radiation Effects Research Foundation (RERF), Hiroshima, Japan.
Keiko
K
Sasaki
Department of Radiobiology/Molecular Epidemiology, Radiation Effects Research Foundation (RERF), Hiroshima, Japan.
Mayumi
M
Maki
Central Research Laboratory, Hiroshima University Faculty of Dentistry, Hiroshima, Japan.
Ikue
I
Hayashi
Department of Statistics, RERF, Hiroshima, Japan.
Kyoji
K
Furukawa
Department of Radiobiology/Molecular Epidemiology, Radiation Effects Research Foundation (RERF), Hiroshima, Japan.
Kengo
K
Yoshida
Department of Radiobiology/Molecular Epidemiology, Radiation Effects Research Foundation (RERF), Hiroshima, Japan.
Junko
J
Kajimura
Department of Radiobiology/Molecular Epidemiology, Radiation Effects Research Foundation (RERF), Hiroshima, Japan.
Seishi
S
Kyoizumi
Department of Radiobiology/Molecular Epidemiology, Radiation Effects Research Foundation (RERF), Hiroshima, Japan.
Yoichiro
Y
Kusunoki
Department of Clinical Studies, RERF, Hiroshima, Japan.
Waka
W
Ohishi
Department of Radiobiology/Molecular Epidemiology, Radiation Effects Research Foundation (RERF), Hiroshima, Japan.
Kei
K
Nakachi
Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.
Nan-Ping
NP
Weng
Department of Radiobiology/Molecular Epidemiology, Radiation Effects Research Foundation (RERF), Hiroshima, Japan.
Tomonori
T
Hayashi
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D015415:Biomarkers / Q000378:metabolism*; D014408:Biomarkers, Tumor; D003430:Cross-Sectional Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007564:Japan; D007962:Leukocytes / Q000378:metabolism* / Q000528:radiation effects*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D054043:Nuclear Weapons; D000069079:Radiation Exposure; D011839:Radiation, Ionizing; D017741:Survivors; D016615:Telomere / Q000528:radiation effects / Q000648:ultrastructure*; D059506:Telomere Shortening
D015415:Biomarkers; D014408:Biomarkers, Tumor
Gerotarget; Hiroshima; aging; ionizing radiation; leukocytes; telomeres