-
Categories
-
Pharmaceutical Intermediates
-
Active Pharmaceutical Ingredients
-
Food Additives
- Industrial Coatings
- Agrochemicals
- Dyes and Pigments
- Surfactant
- Flavors and Fragrances
- Chemical Reagents
- Catalyst and Auxiliary
- Natural Products
- Inorganic Chemistry
-
Organic Chemistry
-
Biochemical Engineering
- Analytical Chemistry
-
Cosmetic Ingredient
- Water Treatment Chemical
-
Pharmaceutical Intermediates
Promotion
ECHEMI Mall
Wholesale
Weekly Price
Exhibition
News
-
Trade Service
No one wants to grow old, whether it's the body or the mind, it's okay to age slowly.
Therefore, the four words "reverse aging" have attracted countless people.
Of course, for the singularity cakes, only methods with scientific evidence count.
Therefore, seeing a new study published by Nature today, Singularity Cake must be introduced.
This study from the Stanford University team shows that "returning the metabolic state of myeloid immune cells such as macrophages to a young state" may be able to reverse brain aging and fight Alzheimer's disease (AD).
This study found that immune cells such as macrophages and microglia in the brain and other parts of the body will undergo changes in their metabolic state with aging, converting more glucose into glycogen storage, resulting in their own energy supply something is wrong.
Immune cells need to consume a lot of energy to work normally, and the state of immune cells with insufficient energy is of course not good.
For example, the phagocytosis of macrophages will decrease, and it will also change to a pro-inflammatory phenotype, thereby promoting aging-related chronic Inflammation.
In the change of the energy status of immune cells, the inflammatory mediator prostaglandin E2 (PGE2) plays a key role.
Therefore, inhibition of PGE2 or its corresponding receptor EP2 not only significantly improves the chronic inflammation state of aging mice, but also reverses cognition The decline of function [1].
If the immune cells are young, the brain will be young.
The breakthrough point of the Stanford team's research is actually PGE2.
Previous studies have shown that patients with neurodegenerative diseases such as AD have higher expression levels of PGE2 [2].
This may also explain that in some studies, long-term use of aspirin is associated with a decreased risk of AD [3], because COX-2 inhibited by aspirin is the upstream signal of PGE2.
The relationship between aspirin, COX-2, PGE2 and EP2.
The research team believes that the effect of PGE2 on brain aging is carried out by changing the metabolic state of immune cells.
Therefore, it first compared the mononuclear cell origin in people over 65 and under 35.
Macrophages (MDMs) found that the synthesis of PGE2 by MDMs in people over 65 years of age increased significantly.
When PGE2 is used to treat young people's MDMs, it can be observed that the glycolysis and oxidative phosphorylation capabilities of cells are significantly reduced, which means that the power of the two most important engines of immune cells has gone wrong.
After treatment with inhibitors targeting the PGE2 receptor EP2, the efficiency of the two metabolic pathways quickly recovered significantly.
In experiments on old mice, the research team re-verified the previous findings: after knocking out the EP2 receptor of mouse myeloid cells (the level of EP2 decreased by 50%), the macrophages of aging mice were relatively healthier, and The Barnes maze experiment showed better spatial memory, suggesting the effect of reversing the aging brain.
Knockout of EP2 directly affected the number and abnormal ratio of mitochondria in macrophages.
Next, the research team dug into the mechanism of the PGE2-EP2 pathway that affects the energy metabolism of macrophages, which is the mechanism mentioned at the beginning of the article: this pathway will promote macrophages.
The phages convert glucose into glycogen, which is then stored in the cell, reducing the level of glucose flow in the cell and affecting the energy supply of the cell.
In fact, this metabolic reprogramming of senescent macrophages is a routine operation of immune cells.
For example, dendritic cells can store glycogen and then use these "strategic reserves" when an inflammatory response is needed, such as infection.
But in aging macrophages, glycogen is really completely sealed, at least not used during the aging process.
As for why macrophages store glycogen, this study did not give an answer, but microglia, which functions similarly to macrophages in the brain, may also have such characteristics.
Studies have shown that a TREM2 mutation that can cause abnormal microglia metabolism is associated with a significant increase in the risk of AD [4].
The last step of the study was to evaluate whether the use of drugs to inhibit EP2 could reverse the aging of the brain in mice, and the result was really a bit surprising: whether it was an inhibitor that could cross the blood-brain barrier and act on microglia, or use an inhibitor that can only Inhibitors that affect macrophages outside of the brain, the brains of mice are showing a trend of youthfulness.
The effect of inhibiting EP2 is that the brain and cells "return to youth".
The editorial issued by "Nature" stated that if the specific mechanism that inhibits the EP2 receptor of peripheral macrophages can be found to make the brain of aging mice younger, it is expected to make the brain rejuvenate.
The research results were quickly transferred to the clinic.
Professor Katrin Andreasson, the corresponding author of this study, also pointed out that precise inhibition of EP2 "may be very difficult.
" For example, the two EP2 inhibitors used in the study are still in the development stage, and the direct use of aspirin to strike is too wide, and there may be Side effects, so we still need to continue to work hard [5].
Scientific research always discovers new problems while solving problems.
Singularity Cake is sure to see new drugs developed based on this paper in the future. Reversing the aging brain, who doesn't want such a medicine? Research motivation is directly full of reference materials: 1.
Minhas PS, Latif-Hernandez A, Mcreynolds MR, et al.
Restoring metabolism of myeloid cells reverses cognitive decline in ageing[J].
Nature, 2021.
2.
Montine TJ, Sidell KR, Crews BC, et al.
Elevated CSF prostaglandin E2 levels in patients with probable AD[J].
Neurology, 1999, 53(7): 1495-1495.
3.
Etminan M, Gill S, Samii A.
Effect of non-steroidal anti-inflammatory drugs on risk of Alzheimer's disease: systematic review and meta-analysis of observational studies[J].
BMJ, 2003, 327(7407): 128.
4.
Ulland TK, Song WM, Huang SCC, et al.
TREM2 maintains microglial metabolic fitness in Alzheimer's disease[J].
Cell, 2017, 170(4): 649-663.
e13.
5.
https:// aging-in-mice-68371 head image source: Pixabay Author of this article | Tan Shuo
Therefore, the four words "reverse aging" have attracted countless people.
Of course, for the singularity cakes, only methods with scientific evidence count.
Therefore, seeing a new study published by Nature today, Singularity Cake must be introduced.
This study from the Stanford University team shows that "returning the metabolic state of myeloid immune cells such as macrophages to a young state" may be able to reverse brain aging and fight Alzheimer's disease (AD).
This study found that immune cells such as macrophages and microglia in the brain and other parts of the body will undergo changes in their metabolic state with aging, converting more glucose into glycogen storage, resulting in their own energy supply something is wrong.
Immune cells need to consume a lot of energy to work normally, and the state of immune cells with insufficient energy is of course not good.
For example, the phagocytosis of macrophages will decrease, and it will also change to a pro-inflammatory phenotype, thereby promoting aging-related chronic Inflammation.
In the change of the energy status of immune cells, the inflammatory mediator prostaglandin E2 (PGE2) plays a key role.
Therefore, inhibition of PGE2 or its corresponding receptor EP2 not only significantly improves the chronic inflammation state of aging mice, but also reverses cognition The decline of function [1].
If the immune cells are young, the brain will be young.
The breakthrough point of the Stanford team's research is actually PGE2.
Previous studies have shown that patients with neurodegenerative diseases such as AD have higher expression levels of PGE2 [2].
This may also explain that in some studies, long-term use of aspirin is associated with a decreased risk of AD [3], because COX-2 inhibited by aspirin is the upstream signal of PGE2.
The relationship between aspirin, COX-2, PGE2 and EP2.
The research team believes that the effect of PGE2 on brain aging is carried out by changing the metabolic state of immune cells.
Therefore, it first compared the mononuclear cell origin in people over 65 and under 35.
Macrophages (MDMs) found that the synthesis of PGE2 by MDMs in people over 65 years of age increased significantly.
When PGE2 is used to treat young people's MDMs, it can be observed that the glycolysis and oxidative phosphorylation capabilities of cells are significantly reduced, which means that the power of the two most important engines of immune cells has gone wrong.
After treatment with inhibitors targeting the PGE2 receptor EP2, the efficiency of the two metabolic pathways quickly recovered significantly.
In experiments on old mice, the research team re-verified the previous findings: after knocking out the EP2 receptor of mouse myeloid cells (the level of EP2 decreased by 50%), the macrophages of aging mice were relatively healthier, and The Barnes maze experiment showed better spatial memory, suggesting the effect of reversing the aging brain.
Knockout of EP2 directly affected the number and abnormal ratio of mitochondria in macrophages.
Next, the research team dug into the mechanism of the PGE2-EP2 pathway that affects the energy metabolism of macrophages, which is the mechanism mentioned at the beginning of the article: this pathway will promote macrophages.
The phages convert glucose into glycogen, which is then stored in the cell, reducing the level of glucose flow in the cell and affecting the energy supply of the cell.
In fact, this metabolic reprogramming of senescent macrophages is a routine operation of immune cells.
For example, dendritic cells can store glycogen and then use these "strategic reserves" when an inflammatory response is needed, such as infection.
But in aging macrophages, glycogen is really completely sealed, at least not used during the aging process.
As for why macrophages store glycogen, this study did not give an answer, but microglia, which functions similarly to macrophages in the brain, may also have such characteristics.
Studies have shown that a TREM2 mutation that can cause abnormal microglia metabolism is associated with a significant increase in the risk of AD [4].
The last step of the study was to evaluate whether the use of drugs to inhibit EP2 could reverse the aging of the brain in mice, and the result was really a bit surprising: whether it was an inhibitor that could cross the blood-brain barrier and act on microglia, or use an inhibitor that can only Inhibitors that affect macrophages outside of the brain, the brains of mice are showing a trend of youthfulness.
The effect of inhibiting EP2 is that the brain and cells "return to youth".
The editorial issued by "Nature" stated that if the specific mechanism that inhibits the EP2 receptor of peripheral macrophages can be found to make the brain of aging mice younger, it is expected to make the brain rejuvenate.
The research results were quickly transferred to the clinic.
Professor Katrin Andreasson, the corresponding author of this study, also pointed out that precise inhibition of EP2 "may be very difficult.
" For example, the two EP2 inhibitors used in the study are still in the development stage, and the direct use of aspirin to strike is too wide, and there may be Side effects, so we still need to continue to work hard [5].
Scientific research always discovers new problems while solving problems.
Singularity Cake is sure to see new drugs developed based on this paper in the future. Reversing the aging brain, who doesn't want such a medicine? Research motivation is directly full of reference materials: 1.
Minhas PS, Latif-Hernandez A, Mcreynolds MR, et al.
Restoring metabolism of myeloid cells reverses cognitive decline in ageing[J].
Nature, 2021.
2.
Montine TJ, Sidell KR, Crews BC, et al.
Elevated CSF prostaglandin E2 levels in patients with probable AD[J].
Neurology, 1999, 53(7): 1495-1495.
3.
Etminan M, Gill S, Samii A.
Effect of non-steroidal anti-inflammatory drugs on risk of Alzheimer's disease: systematic review and meta-analysis of observational studies[J].
BMJ, 2003, 327(7407): 128.
4.
Ulland TK, Song WM, Huang SCC, et al.
TREM2 maintains microglial metabolic fitness in Alzheimer's disease[J].
Cell, 2017, 170(4): 649-663.
e13.
5.
https:// aging-in-mice-68371 head image source: Pixabay Author of this article | Tan Shuo
