This neglected area in the nucleus may hide the "code" of staying young
Covered with "barbed wire", hidden under the nuclear membrane, "garbage" genes are packaged and transported in... The "garbage area" in the nucleus has similar characteristics to the garbage area in the human world: blockade, concealment, garbage packing, and inaccessibility.
On March 28, a paper published online by the "Nature" sub-journal focused on a series of "garbage destruction" cases that occurred in "garbage areas".
Studies have shown that "destroying garbage" can directly induce aging, leading to intractable diseases such as Alzheimer's and atherosclerosis.
Who destroyed these "junk" sequences?
How is it destroyed?
On March 29, Qu Jing, one of the corresponding authors of the paper and a researcher at the Institute of Zoology, Chinese Academy of Sciences, showed reporters a comparison chart of "criminal indication".
The "little yellow cakes" of the young cells on the left are all well-behaved, while the "little yellow cakes" of the old cells on the right enter the garbage area in the nucleus to eat "beans".
"'Bean' represents a protein that stabilizes heterochromatin, just like a 'rope' for packing garbage." Qu Jing explained that after the "bean" is eaten by apolipoprotein E (APOE), the garbage genes are released and activated, which does not The abnormally high expression of the genomic sequence that should be expressed drives human stem cells to accelerate aging and induce a variety of diseases.
Not a simple "lorry driver"
What is Apolipoprotein E?
Under what circumstances would you sneak into the "garbage zone" to do damage?
Many people may have seen it in their medical reports. It can "load" the protein of lipid molecules. Its job should be a "truck driver" responsible for transportation outside the cell or in the cytoplasm.
"This is the first time it has been discovered and confirmed that apolipoprotein E, which is commonly found in blood, can travel back to the nucleus and affect gene expression." Qu Jing told the Science and Technology Daily reporter that most previous research work focused on its extracellular, cytoplasmic (nuclear) outside), rarely mentioning that it functions in the nucleus.
Since abnormal indicators of apolipoprotein E are often associated with senile dementia, vascular sclerosis, and longevity, people have gradually noticed that it is not a simple "truck driver".
"The important role of this protein in the regulation of human health has attracted attention for a long time, and it has long been considered as a key susceptibility gene for aging-related degenerative diseases such as Alzheimer's disease." Qu Jing said, but it has not been found before. A direct link between aging.
The joint research team found that apolipoprotein E accelerated aging by overexpressing it in human stem cells, and knocking out the apolipoprotein E gene by gene editing could delay the aging of human stem cells.
The "suspect" is locked, where is the "crime scene", and how does it "commit the crime"?
Not a Useless Genetic "Junkyard"
"The morphological changes of the nuclear membrane and the loss of heterochromatin have always been one of the important features of human cell aging." Song Mozhi, one of the corresponding authors of the paper and a researcher at the Institute of Zoology, Chinese Academy of Sciences, explained that the abnormality of aging stem cells in the nuclear membrane makes the aging stem cells abnormal. The joint research team locked the "detection" near the nuclear membrane.
"We found that apolipoprotein E aggregated under the nuclear membrane is the culprit in promoting the aging of human stem cells." Song Mozhi said, by analyzing the relationship between apolipoprotein E and inner nuclear membrane proteins, the team found that they are combined with heterochromatin Certain proteins on it can form protein complexes together.
After the complex is formed, the degradation of the nuclear lamina and heterochromatin proteins by lysosomes is accelerated, just like the "eat the beans" shown in the picture, and then the dense chromatin is "unbundled" into loose chromatin, and the DNA inside becomes active , many "junk" genes are transcribed and translated, and then the stem cells begin to age.
The vicinity of the nuclear lamina has always been considered to be a useless gene "garbage dump", but once it is destroyed, it will have a wide range of effects, and even lead to a "dead end" for cells.
"The phenotype of aging is not necessarily a 'subtraction', such as which functions are lost and which factors are inactivated." Song Mozhi said that the search for new mechanisms of aging is "addition", and some should not be expressed Genes are activated and cause irreversible aging.
The shift in thinking will greatly accelerate human understanding of phenomena such as aging.
Professor Liu Qiang from the University of Science and Technology of China believes that these new findings provide important clues and ideas for understanding the pathogenesis of human aging, lifespan regulation, and neurodegenerative diseases.
Mao Zhiyong, a professor at the First Maternal and Infant Health Hospital Affiliated to Tongji University, also believes that this work provides new evidence for the over-activation of repetitive elements to induce cellular and body aging, and suggests new ideas.
According to reports, the research was jointly completed by Liu Guanghui’s research group, Qu Jing’s research group, Song Mozhi’s research group, and Zhang Weiqi’s research group of Beijing Institute of Genomics, Chinese Academy of Sciences. Funded by the Academy of Sciences and Beijing and other projects.