Survivors of Nuclear Weapon Use in Early Life Exhibit Accelerated Immune Aging in Late Life
It probably strains the meaning of the term to call the aftermath of the use of nuclear weapons at the end of the Second World War a natural experiment, but nonetheless there has been considerable study of survivors from those events and their health relative to control populations in other parts of Japan. Irradiation is known to produce what is effectively accelerated aging in the context of cancer treatment, producing an increased burden of senescent cells that then ensure the later course of health for survivors is worse than would otherwise be the case, absent both cancer and treatment. In the case of exposure to radiation deriving from the use of smaller nuclear weapons, analogous lasting effects have emerged.
It is unclear as to how indirect the observed effects on immune function might be most of a lifetime after the event. The researchers here focus on oxidative stress, known to go hand in hand with chronic inflammation. That in turn can arise from an increased burden of senescent cells, but it is far from clear that this is the only (or even primary) mechanism when considering health 50 to 60 years after exposure, rather than the more usual case in medical science of the 10 to 20 years following a later life cancer treatment. Still, the evidence to date suggests that an increased senescent cell burden can last for quite some time, despite the body's demonstrated ability to clear these cells at some pace, even in late life.
In today's open access paper, researchers propose a more T-cell-centric proximate mechanism for immune dysfunction, wherein irradiation leaves behind a lasting tendency for T cells to become more inflammatory, generating more oxidative stress. This may be mediated, carried forward across decades, by alterations in very long-lived memory T cells. How this might relate to underlying mechanisms such as increased cellular senescence following irradiation remains to be resolved.
The immune system matures by deploying a number of responsive lymphocytes in the body and leaving behind memory cells after infection. However, the function of the immune system declines gradually with age, while chronic inflammation and autoimmune responses are enhanced, resulting in metabolic diseases, cardiovascular diseases, cancer, diabetes, and other attributable age-related diseases.
The radiation from the atomic bombs (A-bombs) dropped on Hiroshima and Nagasaki in 1945 has increased the risk of developing certain cancers and non-cancer diseases, including heart disease. Long-term epidemiological and clinical studies of A-bomb survivors have shown that there are significantly increased risks of age- and immune system/inflammation-related diseases among the A-bomb survivors. Although there is no direct evidence that radiation exposure-accelerated immunological aging increases the risk of certain cancers or cardiovascular diseases, it has been presumed that accelerated immunological aging due to radiation exposure is associated with increased risk of age-related diseases.
Reactive oxygen species (ROS) play an important role in immune responses; however, their excessive production and accumulation increases the risk of inflammation-related diseases. Although irradiation is known to accelerate immunological aging, the underlying mechanism is still unclear. To determine the possible involvement of ROS in this mechanism, we examined 10,023 samples obtained from 3,752 atomic-bomb survivors in Hiroshima and Nagasaki, who participated in repeated biennial examinations from 2008 to 2016, for the effects of aging and radiation exposure on intracellular ROS (H2O2 and O2-) levels, percentages of T-cell subsets, and the effects of radiation exposure on the relationship between cell percentages and intracellular ROS levels in T-cell subsets.
The percentages of naïve CD4+ and CD8+ T cells decreased with increasing age and radiation dose, while the intracellular O2- levels in central and effector memory CD8+ T cells increased. Additionally, when divided into three groups based on the percentages of naïve CD4+ T cells, intracellular O2- levels of central, and effector memory CD8+ T cells were significantly elevated with the lowest radiation dose group in the naïve CD4+ T cells. Thus, the radiation exposure-induced decrease in the naïve CD4+ T cell pool size may reflect decreased immune function, resulting in increased intracellular ROS levels in central and effector memory CD8+ T cells, and increased intracellular oxidative stress.
Based on the results of this study, we hypothesize that past radiation exposure, particularly high-dose exposure, affects T-cell function and enhances the persistent inflammatory state, thereby increasing T-cell ROS levels in the blood. To test this hypothesis, we continue to investigate changes in the immune and clinical status with radiation exposure and aging, as well as, an increased risk of disease onset due to radiation exposure in A-bomb survivors, based on interactions between intracellular ROS levels and immune and inflammatory biomarkers. We expect that these studies will provide concrete evidence for the hypothesis of "accelerated immune aging due to radiation exposure".
why do they set the lower bound of the "exposed" group to be 50 mGy? That's medical imaging level radiation. A few CT scans and you are there. And yet seems like they don't focus on that low radiation group after drawing that delineation.
I am late to the party . But I would like to point a bias.
After all, we measure only the survivors of the nukes use. If you bundle all who failed to survive as a control group you would get an amazing result.
Sorry for the off topic.
Party in the fightaging comments. woo hoo!