对于血管衰老来说,DNA损伤反应是一种双刃剑
Xiao Zhang1, Qing Zhao2, Tao Wang3
1Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom; Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China; China International Neuroscience Institute (China-INI), Beijing 100053, China.
Ageing research reviews
|November 25, 2023
概括
血管衰老是心血管疾病的危险因素,受DNA损伤反应 (DDR) 途径的影响. 缺陷和过度活跃的DDR都能加速血管衰老,突出显示DDR在这个过程中的复杂作用.
科学领域:
- 老年学是一门学科.
- 心血管生物学 心血管生物学
- 分子生物学分子生物学
背景情况:
- 血管衰老是与年龄有关的心血管疾病的主要危险因素,对发病率和死亡率有重大贡献.
- 关键的特征包括血管直径增加,内心介质结厚,慢性炎症,化,动脉硬化和动脉样硬化.
- DNA损伤及其反应途径 (DDR) 被认为是血管衰老的关键因素.
研究的目的:
- 审查DNA损伤反应 (DDR) 途径在血管衰老过程中的多方面的作用.
- 探索如何缺陷和过度活跃的DDR机制都会导致血管衰老.
- 在DDR途径中识别潜在的治疗点,以缓解血管衰老.
主要方法:
- 文献综述综合了DDR途径和血管衰老的证据.
- 分析调查DNA损伤积累对血管健康的影响的研究.
- 在血管衰老的背景下,对特定的DDR蛋白 (例如,PARP,ATM) 的研究进行审查.
主要成果:
- 缺乏DDR,导致无法修复的DNA损伤或突变,可以促进血管衰老.
- 过度激活某些DDR蛋白,包括PARP和ATM,也可以加速血管衰老.
- DDR表现出双重作用,不够和过度的活动都会对血管健康产生负面影响.
结论:
- 在血管衰老中,DNA损伤反应途径起着复杂的双重作用.
- 需要进一步的研究,以充分阐明DDR在血管衰老中的机制.
- 了解DDR的作用对于开发针对与年龄有关的心血管疾病的新疗法至关重要.
相关概念视频
02:37DNA Damage can Stall the Cell Cycle
9.2K
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
9.2K
02:25Overview of DNA Repair
31.1K
In order to be passed through generations, genomic DNA must be undamaged and error-free. However, every day, DNA in a cell undergoes several thousand to a million damaging events by natural causes and external factors. Ionizing radiation such as UV rays, free radicals produced during cellular respiration, and hydrolytic damage from metabolic reactions can alter the structure of DNA. Damages caused include single-base alteration, base dimerization, chain breaks, and cross-linkage.
Chemically...
Chemically...
31.1K
01:38Nucleotide Excision Repair
3.5K
DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
3.5K
01:35Mutations
37.9K
Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
37.9K
02:37DNA Damage Can Stall the Cell Cycle
2.6K
2.6K
02:04Fixing Double-strand Breaks
12.6K
The double-stranded structure of DNA has two major advantages. First, it serves as a safe repository of genetic information where one strand serves as the back-up in case the other strand is damaged. Second, the double-helical structure can be wrapped around proteins called histones to form nucleosomes, which can then be tightly wound to form chromosomes. This way, DNA chains up to 2 inches long can be contained within microscopic structures in a cell. A double-stranded break not only damages...
12.6K