Institut de Radioprotection et de Sûreté Nucléaire, Cadarache, 13115, Saint Paul Lez Durance Cedex, France.
IBMM, University of Montpellier, CNRS, ENSCM, Montpellier, France.
Free Radic Biol Med. 2019 Apr;134:657-665. doi: 10.1016/j.freeradbiomed.2019.02.002. Epub 2019 Feb 8.
Living species are chronically exposed to environmental ionizing radiations from sources that can be overexpressed by nuclear accidents. In invertebrates, reproduction is the most radiosensitive studied endpoint, likely to be connected with aging. Surprisingly, aging is a sparsely investigated endpoint after chronic ionizing radiation, whereas understanding it is of fundamental interest in biology and medicine. Indeed, aging and aging-related diseases (e.g., cancer and degenerative diseases) cause about 90% of deaths in developed countries. Therefore, glp-1 sterile Caenorhabditis elegans nematode was used to assess the impact of chronic gamma irradiation on the lifespan. Analyses were performed, at the individual level, on aging and, in order to delve deeper into the mechanisms, at the molecular level, on oxidative damage (carbonylation), biomolecules (lipids, proteins and nucleic acids) and their colocalization. We observed that ionizing radiation accelerates aging (whatever the duration (3-19 days)/dose (0.5-24 Gy)/dose rate (7 and 52 mGy h) tested) leading to a longevity value equivalent to that of wt nematode (∼25-30 days). Moreover, the level of protein oxidative damage (carbonylation) turned out to be good cellular biomarker of aging, since it increases with age. Conversely, chronic radiation treatments reduced carbonylation levels and induced neutral lipid catabolism whatever the dose rate and the final delivered dose. Finally, under some conditions a lipid-protein colocalization without any carbonyl was observed; this could be linked to yolk accumulation in glp-1 nematodes. To conclude, we noticed through this study a link between chronic gamma exposure, lifespan shortening and lipid level decrease associated with a decrease in the overall carbonylation.
活体物种长期暴露于核事故等来源的环境电离辐射中。在无脊椎动物中,繁殖是研究最多的最敏感的研究终点,可能与衰老有关。令人惊讶的是,在慢性电离辐射后,衰老作为一个终点研究得很少,而了解衰老在生物学和医学中具有重要意义。事实上,衰老和与衰老相关的疾病(如癌症和退行性疾病)导致发达国家约 90%的死亡。因此,使用无菌的 glp-1 秀丽隐杆线虫来评估慢性伽马辐射对寿命的影响。在个体水平上进行了衰老分析,并为了更深入地研究机制,在分子水平上进行了氧化损伤(羰基化)、生物分子(脂质、蛋白质和核酸)及其共定位分析。我们观察到,电离辐射加速了衰老(无论测试的持续时间(3-19 天)/剂量(0.5-24Gy)/剂量率(7 和 52mGyh)如何),导致寿命值与 wt 线虫相当(约 25-30 天)。此外,蛋白质氧化损伤(羰基化)水平被证明是衰老的良好细胞生物标志物,因为它随年龄的增加而增加。相反,无论剂量率和最终给予的剂量如何,慢性辐射处理都会降低羰基化水平并诱导中性脂质分解代谢。最后,在某些条件下,观察到没有羰基的脂质-蛋白质共定位;这可能与 glp-1 线虫中卵黄的积累有关。总之,通过这项研究,我们注意到慢性伽马辐射暴露、寿命缩短和脂质水平降低之间存在联系,这与整体羰基化程度降低有关。