老化是由改变的端粒状态引起的,而不是端粒损失
Jan Karlseder1, Agata Smogorzewska, Titia de Lange
1Laboratory for Cell Biology and Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
Science (New York, N.Y.)
|March 30, 2002
概括
过度表达的TRF2,一个端粒DNA结合蛋白,加速端粒缩短,但通过防止染色体融合,延迟复制性衰老. 衰老是由改变的端粒保护引发的,而不仅仅是DNA损失.
科学领域:
- 细胞衰老 细胞衰老
- 端粒生物学 端粒生物学
- 老龄化的分子机制.
背景情况:
- 由于被编程的端粒缩短,原始人体细胞停止分裂并进入复制性衰老.
- 推动这种转型的精确机制仍然不完全理解.
研究的目的:
- 为了研究TRF2的作用,一个端粒DNA结合蛋白,在调节端粒长度和复制性衰老.
- 阐明引发衰老开始的分子事件.
主要方法:
- 在人体培养中的原始细胞中,TRF2过度表达.
- 对端粒长度动态和染色体端到端融合的分析.
- 测量衰老开始和衰老时的端粒长度的量化.
主要成果:
- 过度表达TRF2加速了端粒的缩短,但没有加速衰老.
- TRF2显著降低了开始衰老的端粒长度值 (衰老设定点) 从7到4千基.
- 在接近衰老的细胞中,TRF2有效地保护了临界短的端粒免受融合,并抑制了染色体末端的融合.
结论:
- 复制衰老是由缩短的端粒的保护状态的变化引起的,而不是完全缺少端粒DNA.
- 尽管TRF2促进了更快的端粒缩短,但它通过保持端粒完整性和防止融合来延缓衰老.
相关概念视频
02:31Replication in Eukaryotes
Overview
02:41Telomeres and Telomerase
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 DNA.
02:15Replicative Cell Senescence
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 the telomeric...
01:29Replication in Eukaryotes
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...
02:41Telomeres and Telomerase
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 DNA.
02:15Replicative Cell Senescence
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 the telomeric...