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Impact of aging on gene expression response to x-ray irradiation using mouse blood

ABSTRACT: Impact of aging on gene expression response to x-ray irradiation using mouse blood

PROVIDER: PRJNA548357 | ENA |

REPOSITORIES: ENA

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Project description:Background: In the event of an improvised nuclear device or radiological dirty bomb detonation large numbers of people will be exposed to radiation that would require a timely and accurate biodosimetry to identify the highly exposed individuals who would require medical treatment from those who have received low or no radiation (the “worried well”). Gene expression signatures in response to radiation have been derived from mice and human peripheral blood and the impact of a number of variables, such as dose, time, genotype, and gender, on gene expression has been analyzed. However, the impact of aging on radiation gene profiling has not been taken into consideration. Results: Global gene expression was measured in the blood of young (2 mo) and old (21 mo) male C57BL/6J mice 1 day after they were exposed to 4 Gy x-rays or they were sham irradiated (control) using the Agilent Mouse Whole Genome microarrays. Animals exposed to radiation suppressed expression of DNA repair genes with fold-changes being very similar to the two age groups. A notable exception was Mismatch Repair (MMR) that was significantly enriched among the downregulated genes in irradiated old mice (p = 2.34E-09) compared with irradiated young mice (p = 1.62E-04). Furthermore, cardiac hypertrophy signaling (p < 0.002) and the role of NFAT in cardiac hypertrophy (p = 0.01) were predicted to be enriched among the upregulated differentially expressed genes in irradiated old mice, but not irradiated young mice. In contrast, young mice respond to x-ray exposure by significantly upregulating genes involved in phagosome formation (p = 3.09E-07), phagosome maturation (p = 0.001), and Fcγ receptor-mediated phagocytosis (p = 0.03), all crucial processes that eliminates apoptotic cells and preserve tissue homeostasis. Conclusions: We show that age is a variable that has the potential to fundamentally alter the transcriptomic profile of irradiated mouse blood. A number of biological processes, including phagocytosis, are differentially represented in young and old mice exposed to x-ray radiation. Our results highlight the significance of age as a variable that can have profound biological effects that will affect medical management and treatment decisions in case of a radiological emergency.

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Impact of aging on gene expression response to x-ray irradiation using mouse blood

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