针对衰老中的DNA损伤:朝着超级充电DNA修复的方向
Arturo Bujarrabal-Dueso1,2, George A Garinis3,4, Paul D Robbins5
1Institute for Genome Stability in Aging and Disease, University and University Hospital of Cologne, Cologne, Germany.
Nature reviews. Drug discovery
|June 12, 2025
概括
打击与年龄相关疾病的主要危险因素 - - 衰老,是关键战略. DNA损伤是一种因果衰老机制,增强DNA修复可能会延缓衰老和预防疾病.
科学领域:
- 老年学和分子生物学
- 遗传学和表观遗传学
- 细胞和分子医学 细胞和分子医学
背景情况:
- 老龄化是人类主要疾病 (如癌症,糖尿病和心血管疾病) 的首要危险因素.
- 对模型生物的干预已经延长了寿命和健康寿命,但它们与衰老机制的因果关系仍然不清楚.
- 身体DNA损伤是衰老的重要因果机制,损害细胞功能,导致衰老,亡和突变.
研究的目的:
- 审查针对DNA损伤后果的进展,并加强DNA修复以减轻衰老.
- 讨论缓解DNA损伤影响的药理方法.
- 探索延缓衰老,预防癌症和减少与年龄有关的疾病的策略.
主要方法:
- 关于衰老,DNA损伤和DNA修复机制的科学文献的审查.
- 对模型生物的遗传和药理干预的分析.
- 讨论新出现的概念和治疗策略.
主要成果:
- 证据强烈表明,DNA损伤是衰老过程中的因果机制.
- 针对DNA损伤后果和修复能力的干预措施在模型生物中显示出希望.
- 药理减轻DNA损伤效应是一个正在发展的战略.
结论:
- 针对DNA损伤和增强修复是对抗衰老和与年龄有关的疾病的合理策略.
- 药理干预具有延缓衰老和预防退行性疾病的潜力.
- 需要进一步的研究来将这些发现转化为人类疗法.
相关概念视频
Overview of DNA Repair
30.9K
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...
30.9K
Nucleotide 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
DNA Damage can Stall the Cell Cycle
9.1K
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...
9.1K
DNA Damage Can Stall the Cell Cycle
2.6K
2.6K
Fixing Double-strand Breaks
12.5K
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...
12.5K
Replication in Eukaryotes
13.6K
In eukaryotic cells, DNA replication is highly conserved and tightly regulated. Multiple linear chromosomes must be duplicated with high fidelity before cell division, so there are many proteins that fulfill specialized roles in the replication process. Replication occurs in three phases: initiation, elongation, and termination, and ends with two complete sets of chromosomes in the nucleus.
Many Proteins Orchestrate Replication at the Origin
Eukaryotic replication follows many of the same...
Many Proteins Orchestrate Replication at the Origin
Eukaryotic replication follows many of the same...
13.6K


