解剂减少内皮细胞的DNA损伤和端粒功能障碍,尽管减少了端粒的长度
Samuel I Bloom1, Eric Tuday2,3, Torikul Islam1
1Department of Nutrition and Integrative Physiology, The University of Utah, Salt Lake City, UT, USA.
Aging biology
|March 20, 2025
概括
衰老药物,达沙替尼和奎尔丁 (D+Q),小鼠中的明确衰老的内皮细胞. 这种治疗减少了细胞损伤和衰老的标志,改善了老年动物的血管健康.
科学领域:
- 老年学是一门学科.
- 心血管生物学 心血管生物学
- 细胞生物学 细胞生物学
背景情况:
- 衰老导致细胞衰老,特别是在内皮细胞中,导致心血管疾病.
- 老化剂在细胞培养中减少细胞衰老方面表现有前途.
- 需要进行翻译性研究来证实老化疗效和对细胞衰老的影响.
研究的目的:
- 调查老化尾酒达沙替尼和奎尔塞丁 (D+Q) 对老年小鼠老化的内皮细胞的in vivo影响.
- 为了确定D+Q治疗是否能减少内皮细胞中细胞衰老的标志.
- 评估D+Q对老化内皮细胞中DNA损伤和端粒功能障碍的影响.
主要方法:
- 年长的小鼠 (24个月大) 接受了D+Q或载体控制的治疗.
- 测量了动脉内皮细胞中的基因表达,以评估衰老.
- 在肺内皮细胞中分析了DNA损伤,端粒功能障碍和端粒长度.
主要成果:
- D+Q治疗显著降低了动脉内皮细胞中的基因表达,表明衰老的减少.
- 在D+Q治疗后,较少的肺内皮细胞显示DNA损伤和端粒功能障碍.
- D+Q治疗缩短了内皮细胞中的端粒长度,但并没有达到严重功能障碍的水平.
结论:
- 老化尾酒D+Q有效清除老年小鼠体内老化的内皮细胞in vivo.
- D+Q治疗减少了细胞衰老的关键标志,包括DNA损伤和端粒功能障碍,在内皮细胞中.
- 清除衰老细胞会留下一个更健康的内皮细胞群,血管衰老的迹象更少.
相关概念视频
Telomeres and Telomerase
22.9K
In eukaryotic DNA replication, a single-stranded DNA fragment remains at the end of a chromosome after the removal of the final primer. This section of DNA cannot be replicated in the same manner as the rest of the strand because there is no 3’ end to which the newly synthesized DNA can attach. This non-replicated fragment results in gradual loss of the chromosomal DNA during each cell duplication. Additionally, it can induce a DNA damage response by enzymes that recognize single-stranded...
22.9K
Replicative Cell Senescence
3.6K
Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds...
3.6K
Replication in Eukaryotes
12.9K
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...
12.9K
DNA Damage can Stall the Cell Cycle
9.0K
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...
9.0K
Overview of DNA Repair
29.8K
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...
29.8K
Translesion DNA Polymerases
9.7K
Translesion (TLS) polymerases rescue stalled DNA polymerases at sites of damaged bases by replacing the replicative polymerase and installing a nucleotide across the damaged site. Doing so, TLS allows additional time for the cell to repair the damage before resuming regular DNA replication.
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...
9.7K


