DNA damage and repair in old and young and in participants in the BLSA

双链断裂是DNA中非常危险的损伤，必须修复才能使细胞完成复制和转录。在双链断裂修复方面有缺陷的细胞容易受到基因组的不稳定，而有这些缺陷的个体患癌症的风险往往更高。双链断裂的存在可以通过检查细胞中一种被称为H_2AX的组蛋白变体的磷酸化形式来确定。蛋白质的磷酸化在双链断裂附近迅速发生，并持续到断裂被修复。因此，磷酸-H_2AX(g-H_2AX)可作为断裂的替代标志物。免疫荧光技术可以很容易地检测到这种物种，因此可以在单细胞中检测到。我们试图测试这一假设，即与年轻个体相比，老年个体细胞中双链断裂的水平较高。我们的分析表明，g-H_2AX焦点随着年龄的增加呈线性增加，在57岁时达到峰值。我们发现，有已知维生素D缺乏史的人以及57岁/岁的高血压患者的病灶显著增加。我们的结果支持DNA损伤增加在年龄相关疾病发病率中的作用，g-H_2AX可能是人类年龄相关疾病发病率的生物标志物。我们目前正在研究-H2AX基因与不同临床疾病的相关性，这些疾病已知与基因组不稳定和/或氧化应激有关。 &#8195；

Double strand breaks are very dangerous lesions in DNA and must be repaired to allow cells to complete replication and transcription. Cells with deficiencies in double strand break repair are subject to genomic instability and individuals with these deficiencies are often at elevated risk for cancer. The presence of double strand breaks can be determined by examining cells for the phosphorylated form of a histone protein variant known as H2AX. Phosphorylation of the protein occurs rapidly in the vicinity of a double strand break, and persists until the break is repaired. Consequently phospho-H2AX (g-H2AX) serves as a surrogate marker for breaks. This species can be easily detected by immunofluorescence techniques, and thus can be detected in single cells. We sought to test the hypothesis that double strand breaks are present in elevated levels in cells from aged individuals, as compared with younger individuals. Our analysis reveals that g-H2AX foci increase in a linear fashion with regards to age, peaking at 57 years. We found a significant increase in foci in individuals with a known history of vitamin D deficiency as well as in individuals 57 y/o with hypertension. Our results support a role for increased DNA damage in the morbidity of age-related diseases and that g-H2AX may be a biomarker for human morbidity in age-related diseases. We are currently investigating the correlations between -H2AX foci and different clinical diseases which are known to be associated with genome instability and/or oxidative stress.