Telomeres are end structure of chromosome and essential in maintaining chromosome integrity and in controlling cellular replication. Attrition of telomere length in peripheral blood mononuclear cells (PBMCs) with age is well documented from cross-sectional studies. But the actual in vivo changes in telomere lengths and its relationship with the contributing factors within individuals with age have not been fully addressed. In addition, 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. Alterations in the number and composition of lymphocytes and their subsets in blood are considered a hallmark of immune system aging. However, it is unknown whether the rates of change of lymphocytes are stable or change with age, or whether the inter-individual variations of lymphocyte composition are stable over time or undergo different rates of change at different ages. Here, we report a longitudinal analysis of T- and B-cells and their subsets, and NK cells in the blood of 165 subjects aged from 24 to 90 years, with each subject assessed at baseline and an average of 5.6 years follow-up. The rates of change of T-(CD4+ and CD8+) and B-cells, and NK cells were relative stable throughout the adult life. A great degree of individual variations in numbers of lymphocytes and their subsets and in the rates of their changes with age was observed. Among them, CD4+ T cells exhibited the highest degree of individual variation followed by NK cells, CD8+ T cells, and B cells. Different types of lymphocytes had distinct trends in their rates of change which did not appear to be influenced by CMV infection. Finally, the rates of CD4+, CD8+ T cells, naive CD4+ and nave CD8+ T cells were closely positively correlated. Our findings provide evidence that the age-associated changes in circulating lymphocytes were at relative stable rates in vivo in a highly individualized manner and the levels of selected cytokines/cytokine receptors in serum might influence these age-associated changes of lymphocytes in circulation.
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