无处不在的蛋白质组的重新连接决定了C. elegans的衰老
Seda Koyuncu1, Rute Loureiro1, Hyun Ju Lee1
1Cologne Excellence Cluster for Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
Nature
|July 29, 2021
概括
细胞完整性随着年龄的增长而下降. 恢复蛋白质降解途径可以通过向与年龄相关的蛋白质来延长寿命.
科学领域:
- 细胞生物学
- 老年学
- 生物化学
背景情况:
- 衰老的特征是细胞的完整性下降.
- 乌比基的修饰在细胞功能中起着至关重要的作用.
- 了解无处不在和衰老之间的联系对于长寿研究至关重要.
研究的目的:
- 探讨无处不在和衰老过程之间的关系.
- 为了确定在老化过程中无处不在的特征如何变化.
- 确定改变蛋白质降解对寿命的影响.
主要方法:
- 在Caenorhabditis elegans中测量整个蛋白质组的泛素特征.
- 在饮食限制和降低胰岛素信号下对无处不在的蛋白质组变化的分析.
- 整合具有缺陷蛋白酶的虫数据以确定年龄累积的点.
主要成果:
- 衰老导致无处不在的蛋白质组的重塑,其特征是由于duebiquitinase活性增加而导致的全球无处不在的损失.
- 随着年龄的增长,蛋白体标会积累,因为随之降低了无处不在和随后的降解.
- 降低受年龄调节的蛋白酶标水平会延长寿命,同时防止它们的降解会缩短寿命.
结论:
- 针对性蛋白质降解的与年龄相关的变化显著影响了寿命.
- 特定的蛋白质如IFB-2和EPS-8被确定为关键的年龄失调的蛋白质体标.
- 针对蛋白质降解途径的干预措施有可能延长寿命.
相关概念视频
The Proteasome
Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
Regulated Protein Degradation
It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Proteins: From Genes to Degradation
Within a biological system, the DNA encodes the RNA, and the nucleotide sequence in the RNA further defines the amino acid sequence in the protein. This is referred to as “The Central Dogma of Molecular Biology” - a term coined by Francis Crick. Central dogma is a firm principle in biology that defines the flow of genetic information within any life form. The two fundamental steps in central dogma are - transcription and translation.
Transcription is the synthesis of RNA molecules by RNA...
Transcription is the synthesis of RNA molecules by RNA...
Replicative 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...
Proteins: From Genes to Degradation
Within a biological system, the DNA encodes the RNA, and the nucleotide sequence in the RNA further defines the amino acid sequence in the protein. This is referred to as “The Central Dogma of Molecular Biology” - a term coined by Francis Crick. Central dogma is a firm principle in biology that defines the flow of genetic information within any life form. The two fundamental steps in central dogma are - transcription and translation.
Transcription is the synthesis of RNA molecules by RNA...
Transcription is the synthesis of RNA molecules by RNA...
The Proteasome
Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3 (ubiquitin...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3 (ubiquitin...


