Abstract

The ageing process is a multifactorial phenomenon, associated with decreased physiological and cellular functions and an increased propensity for various degenerative diseases. Studies on melatonin (N-acetyl-5-methoxytryptamine), a potent antioxidant, are gaining attention since melatonin production declines with advancing age. Hence, the aim of this study was to evaluate the effects of chronic melatonin consumption on genotoxic and mutagenic parameters of old Swiss mice. Herein, 3-month-old Swiss albino male mice (n = 240) were divided into eight groups and subdivided into two experiments: first (three groups): natural ageing experiment; second (five groups): animals that started water or melatonin supplementation at different ages (3, 6, 12 and 18 months) until 21 months. After 21 months, the animals from the second experiment were euthanized to perform the comet assay, micronucleus test and western blot analysis. The results demonstrated that melatonin prolonged the life span of the animals. Relative to genomic instability, melatonin was effective in reducing DNA damage caused by ageing, presenting antigenotoxic and antimutagenic activities, independently of initiation age. The group receiving melatonin for 18 months had high levels of APE1 and OGG1 repair enzymes. Conclusively, melatonin presents an efficient antioxidant mechanism aiding modulating genetic and physiological alterations due to ageing.

中文翻译：

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在不同时期补充褪黑激素直到衰老调节小鼠的遗传毒性参数

摘要

衰老过程是一种多因素现象，与生理和细胞功能下降以及各种退行性疾病的倾向增加有关。褪黑激素（N-acetyl-5-methoxytryptamine）是一种有效的抗氧化剂，由于褪黑激素的产生随着年龄的增长而下降，因此对褪黑激素（N-acetyl-5-methoxytryptamine）的研究受到关注。因此，本研究的目的是评估长期服用褪黑激素对瑞士老年小鼠基因毒性和诱变参数的影响。在此, 3 个月大的瑞士白化雄性小鼠 ( n= 240）分为八组，再细分为两个实验：第一（三组）：自然老化实验；第二组（五组）：在不同年龄（3、6、12 和 18 个月）至 21 个月时开始补充水或褪黑激素的动物。21 个月后，对来自第二个实验的动物实施安乐死以进行彗星试验​​、微核试验和蛋白质印迹分析。结果表明，褪黑激素延长了动物的寿命。相对于基因组不稳定性，褪黑激素可有效减少由衰老引起的 DNA 损伤，呈现抗原毒性和抗诱变活性，与起始年龄无关。接受褪黑激素 18 个月的组具有高水平的 APE1 和 OGG1 修复酶。最终，