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

老年人、年轻人以及 BLSA 参与者的 DNA 损伤和修复

• 批准号: 8148300
• 负责人: Vilhelm Bohr
• 金额: $ 14.26万
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8148300
• 关键词: DNA; DNA Damage; DNA Repair; Double Strand Break Repair; Normal Cell; Participant

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 of 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 serves a surrogate marker for breaks. This species can be easily detected by immunofluorescence techniques, and thus can be detected in single cells. We are testing the hypothesis that double strand breaks are present in elevated levels in cells from aged individuals, as compared with younger individuals, by determining the level of phospho-H2AX in blood derived cells from donors in the BLSA program. The results indicate that cells from older individuals contain more frequent H2AX sites than cells from younger individuals. We have currently enrolled 45 participants in this study and are seeking to gain additional younger patients < 59 and older patients >79 yr old to increase the statistical power of the study.

双链断裂是DNA中非常危险的病变，必须修复以允许细胞完成复制和转录。双链断裂修复中缺乏不足的细胞受到基因组不稳定性的影响，并且患有这些缺陷的个体通常处于癌症的风险升高。双链断裂的存在可以通过检查细胞的组蛋白变体的磷酸化形式称为H2AX。蛋白质的磷酸化迅速发生在双链断裂的附近，并一直持续到断裂。因此，磷酸-H2AX为断裂提供了替代标记。可以通过免疫荧光技术轻松检测该物种，因此可以在单个细胞中检测到。我们正在检验以下假设：与年轻个体相比，与年轻个体相比，通过确定BLSA计划中供体的血液衍生细胞中磷酸-H2AX的水平，在老年人的细胞中存在双链断裂。结果表明，来自老年人的细胞包含的H2AX位点比来自年轻个体的细胞更频繁。我们目前已经招募了45名参与者参加这项研究，并寻求增加<59岁及以> 79岁的年轻患者以增加研究的统计能力。