The aging phenomenon is associated with oxidative stress damage in biomolecules, especially DNA. 5-Methyltetrahydrofolate (5-MTHF), the active folate form, plays a pivotal role in maintaining genomic integrity. However, recently it was associated with cancer development. In Brazil, there are folic acid enriched foods, such as flour, making the general population chronically exposed to folates. Therefore, the aim of this study was to investigate whether erythrocytes 5-MTHF levels were associated with age-related DNA damage in two groups (elderly and young subjects). Additionally, a study in Caenorhabditis elegans, an in vivo alternative model, was performed to verify if 5-MTHF presents a pro-oxidant effect. A total of 50 elderly and 25 young subjects participated in this study, which analyzed whole blood DNA damage, plasma carbonyl proteins (PCO), and erythrocytes 5-MTHF levels. In addition, ROS and RNS production, survival rate, and lifespan were performed in C. elegans exposed to 5-MTHF. Blood 5-MTHF levels and DNA damage were increased in the elderly compared to the young group. A positive association was found between 5-MTHF levels and DNA damage, and between DNA damage and PCO levels, suggesting an oxidative cause of damage associated with the active folate form. In an experimental study it was observed that 5-MTHF increased ROS production in C. elegans, in a dose dependent manner, while survival rate and life span were not affected at the test doses. These findings suggest that 5-MTHF, the active folate form, may be involved in DNA damage in the elderly. This damage could be a result of oxidative stress, as observed in the in vivo alternative model; however, more studies are necessary to prove our present results.

中文翻译：

---

老年人的DNA损伤与5-MTHF水平有关：一种促氧化剂活性。

老化现象与生物分子，尤其是DNA的氧化应激损伤有关。叶酸形式的5-甲基四氢叶酸（5-MTHF）在维持基因组完整性方面起着关键作用。然而，最近它与癌症的发展有关。在巴西，富含叶酸的食物（例如面粉）使普通人群长期暴露于叶酸中。因此，本研究的目的是调查两组（老年人和年轻人）中红细胞5-MTHF水平是否与年龄相关的DNA损伤有关。另外，在体内秀丽隐杆线虫（Caenorhabditis elegans）中进行了一项研究，以验证5-MTHF是否具有促氧化剂作用。共有50位老年人和25位年轻受试者参加了这项研究，该研究分析了全血DNA损伤，血浆羰基蛋白（PCO），和红细胞5-MTHF水平。另外，在暴露于5-MTHF的秀丽隐杆线虫中进行ROS和RNS的产生，存活率和寿命。与年轻人相比，老年人的血液5-MTHF水平和DNA损伤增加。发现5-MTHF水平与DNA损伤之间以及DNA损伤与PCO水平之间存在正相关，表明与活性叶酸形式相关的损伤的氧化原因。在一项实验研究中，观察到5-MTHF以剂量依赖的方式增加了秀丽隐杆线虫中ROS的产生，而在测试剂量下存活率和寿命不受影响。这些发现表明，活性叶酸形式的5-MTHF可能参与了老年人的DNA损伤。如在体内替代模型中所观察到的，这种损害可能是氧化应激的结果。然而，