Department of Biosciences, University of Durham, Mountjoy Science Site, South Road, Durham, DH1 3LE, UK; Biophysical Sciences Institute, University of Durham, Mountjoy Science Site, South Road, Durham, DH1 3LE, UK.
Radiation Safety Research Center, Nuclear Technology Research Laboratory, Central Research Institute of Electric Power Industry (CRIEPI), Komae, Tokyo, Japan.
Mutat Res Rev Mutat Res. 2019 Jan-Mar;779:68-81. doi: 10.1016/j.mrrev.2019.02.004. Epub 2019 Feb 15.
Ionizing radiation (IR) damages DNA and other macromolecules, including proteins and lipids. Most cell types can repair DNA damage and cycle continuously their macromolecules as a mechanism to remove defective proteins and lipids. In those cells that lack nuclei and other organelles, such as lens fiber cells and mammalian erythrocytes, IR-induced damage to macromolecules is retained because they cannot be easily replenished. Whilst the life span for an erythrocyte is several months, the life span of a human lens is decades. There is very limited turnover in lens macromolecules, therefore the aging process greatly impacts lens structure and function over its lifetime. The lens is a tissue where biomolecular longevity, lifelong retention of its components and continued growth are integral to its homeostasis. These characteristics make the lens an excellent model to study the contribution of retained macromolecular damage over time. Epidemiological data have revealed a significant association between exposure to IR, the loss of lens optical function and the formation of cataracts (cataractogenesis) later in life. Lifestyle, genetic and environmental factors all contribute to cataractogenesis due to their effect on the aging process. Cataract is an iconic age-related disease in humans. IR is a recognised cause of cataract and the occupational lens dose limit is reduced from 150 to 20 mGy / year averaged over 5 years (ICRP Publication 118). Understanding the effects of low dose IR on the lens and its role in cataractogenesis is therefore very important. So we redefine "cataractogenic load" as a term to account for the combined lifestyle, genetic and environmental processes that increase biomolecular damage to lens macromolecules leading to cataract formation. These processes weaken metabolic defenses, increase post-translational protein modifications, and alter the lipid structure and content of the lens. IR exposure is a significant insult to the lens because of free radical generation and the ensuing oxidative stress. We support the concept that damage caused by IR compounds the aging process by increasing the cataractogenic load, hereby accelerating lens aging and its loss of function.
电离辐射 (IR) 会损害 DNA 和其他生物大分子，包括蛋白质和脂质。大多数细胞类型可以修复 DNA 损伤，并不断循环其生物大分子，作为清除有缺陷的蛋白质和脂质的机制。在那些缺乏细胞核和其他细胞器的细胞中，如晶状体纤维细胞和哺乳动物红细胞，由于无法轻易补充，IR 引起的生物大分子损伤会被保留下来。虽然红细胞的寿命为数月，但人眼晶状体的寿命为几十年。晶状体生物大分子的更新非常有限，因此衰老过程会极大地影响晶状体的结构和功能。晶状体是一种组织，其中生物分子的寿命、其成分的终生保留和持续生长是其体内平衡的组成部分。这些特征使晶状体成为研究随时间保留的生物大分子损伤的贡献的理想模型。流行病学数据显示，暴露于 IR 与晶状体光学功能丧失以及晚年白内障（白内障形成）的形成之间存在显著关联。生活方式、遗传和环境因素都会因影响衰老过程而导致白内障形成。白内障是人类标志性的年龄相关性疾病。IR 是白内障的公认原因，职业晶状体剂量限值已从 150 减少到 20 mGy/年，平均 5 年（ICRP 出版物 118）。因此，了解低剂量 IR 对晶状体的影响及其在白内障形成中的作用非常重要。因此，我们重新定义“白内障形成负荷”一词，以说明增加晶状体生物大分子损伤导致白内障形成的生活方式、遗传和环境综合过程。这些过程削弱了代谢防御能力，增加了翻译后蛋白质修饰，并改变了晶状体的脂质结构和含量。由于自由基的产生和随之而来的氧化应激，IR 暴露对晶状体是一种严重的伤害。我们支持这样一种观点，即 IR 造成的损伤通过增加白内障形成负荷来加速晶状体衰老及其功能丧失，从而加速衰老过程。
