Abstract
Ionizing Radiation (IR), especially at high doses, induces cellular senescence in exposed cultures. IR also induces “bystander effects” through signals released from irradiated cells, and these effects include many of the same outcomes observed following direct exposure. Here, we investigate if radiation can cause senescence through a bystander mechanism. Control cultures were exposed directly to 0, 0.1, 2, and 10 Gy. Unirradiated cells were treated with medium from irradiated cultures or with exosomes extracted from irradiated medium. The level of senescence was determined post-treatment (24 h, 15 days, 30 days, and 45 days) by β-galactosidase staining. Media from cultures exposed to all four doses, and exosomes from these cultures, induced significant senescence in recipient cultures. Senescence levels were initially low at the earliest timepoint, and peaked at 15 days, and then decreased with further passaging. These results demonstrate that senescence is inducible through a bystander mechanism. As with other bystander effects, bystander senescence was induced by a low radiation dose. However, unlike other bystander effects, cultures recovered from bystander senescence after repeated passaging. Bystander senescence may be a potentially significant effect of exposure to IR, and may have both beneficial and harmful effects in the context of radiotherapy.
Highlights
IntroductionCellular senescence is triggered by various factors such as telomere attrition, enhanced oxidative stress, and accumulation of DNA damage [1]
These results demonstrate the existence of a radiation-activated media transfer senescence bystander effect, and that exosomes are one media component that contains senescence-inducing signals
Our results confirm the existence of a radiation-induced senescence bystander effect
Summary
Cellular senescence is triggered by various factors such as telomere attrition, enhanced oxidative stress, and accumulation of DNA damage [1]. Recent research has demonstrated that the SASP’s potent autocrine and paracrine activities induce inflammation and fibrosis, induce malignant phenotypes, and attract immune cells to senescent cells themselves and the neighboring cells, which change tissue microenvironments and lead to aging and age-related diseases [1,4,5,6]. Recent study showed that senescent cells secreted bioactive factors into the blood that changed hemostasis and drove blood clotting [7]. These SASP factors could work as plasma biomarkers for aging and age-related diseases that are distanced by the existence of senescent cells [8]
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