Brain aging can be reversed, just inject young cerebrospinal fluid, “rejuvenate” in Nature

“Old man, can’t remember.”

As the age continues to grow, many people will make such a sigh – the memory gradually declines. So is there a way to make this natural phenomenon “defeating”?

Nature says: Yes.

A new study published by Stanford University in Nature found:

Injecting the cerebrospinal fluid (CSF) of young mice into the brains of older mice improves their memory!

Specifically,40% A few weeks after implanting the cerebrospinal fluid of the “little fresh meat”, the old mice could still recall the stress experiments they had experienced before.

In contrast to the control group, this data for that wave of aged mice was only 18%.

(In this process, there is quite a feeling of “sucking stars”)

The researchers believe that this method of directly perfusing young cerebrospinal fluid can improve old mice.Conductivity of neuronsthereby improving the process of memory formation and recall.

In this regard, Maria Lehtinen, an expert at Boston Children’s Hospital and a neurologist at Harvard Medical School, said:

This is the first study to show that injecting cerebrospinal fluid can actually improve cognitive function, so this study is a milestone.

The new directions it opens are very exciting, and we can use cerebrospinal fluid as a treatment for a variety of diseases.

Some netizens believe that this will be “Hope for Alzheimer’s“.

“Suck” young cerebrospinal fluid, and the brain “rejuvenates”

It is not difficult to see that in this Stanford study,cerebrospinal fluidIt is the key point to wear the protagonist’s halo.

It is a colorless and transparent fluid found mainly in our ventricles and subarachnoid space:

Cerebrospinal fluid surrounds and supports the entire brain and spinal cord, and plays a protective role in trauma; it also plays the role of lymphatic fluid in other parts of the body – clearing metabolites and inflammatory exudates.

Based on this, researchers have launched an experiment to “rejuvenate” the aging brain.

The first to appear is “Seniors” – 18 20 monthsbig mouse.

The team first gave each “senior group” member’s foot 3 timesmild electric shock, the shock is accompanied by several flashes and sounds.The purpose of this is to allow them to form a specialmemorythat is, the pain sensation of the electric shock is connected to the external stimulus (flash, sound).

Then came the “Little Fresh Meat Group” — only young 10 weeksbig mouse. After the researchers anesthetized the “little fresh meat”, they extracted cerebrospinal fluid from their brains, about 10 microliters at a time, which is about one-tenth the volume of a drop of blood.

When the team has collected enough approx. 90 µlcerebrospinal fluid, they are placed in a specific container and implanted in 8The back of a “senior group” mouse.

The cerebrospinal fluid of the “small fresh meat” in the container will be 7 daysOver time, it will slowly enter the brain of the “senior group” mice through a small tube.

and in addition 10“senior group” mice ascontrol groupthen under the same experimental conditions, the injectionartificial cerebrospinal fluid. Next, is the moment to witness the miracle.

After another 12 days (three weeks after receiving the stimulus memory), the researchers asked the “senior group” to face the external stimulus again. That is, the flashes and sounds that accompany the electric shock at that time, so as to see if they will remember that paragraph”painful memory“.

The results show,nearly 40%Aged mice that “suck” young cerebrospinal fluid show stress responses such as fear when exposed to external stimuli.

In contrast, in aged mice injected with artificial cerebrospinal fluid, only 18% “Painful memories”.

Therefore, the researchers believe that young cerebrospinal fluid may restore some of the capabilities of the aging brain. As study co-author Tony Wyss-Coray, a neuroscientist at Stanford University, said:

The broader implication of this research is that aging brains are still plastic, and there are ways to improve their function.

Why is this happening?

To find out why young cerebrospinal fluid affects memory, the researchers analyzed the hippocampus of older mice.

It was found that 6 days after injection of young CSF, in the hippocampus of aged mice, theOligodendrocytes (Oligendrocyte) gene expression was significantly increased.

Oligodendrocytes are cells that produce myelin sheaths at the ends of neurons. The resulting myelin sheath is rich in fats and proteins that encase neuronal axons.

In simple terms, it can be compared toInsulation on the outside of the wire.

The role is similar, mainly to ensure more smooth information transmission between internal neurons.

Looking further, the proliferation of oligodendrocyte precursor cells is related tooligodendrocyte precursor cells(OPC) related.

Researchers found that oligodendrocyte precursor cells in the hippocampus of aged mice increased after infusion of young cerebrospinal fluid 1x more. After 3 weeks of cell proliferation, myelin sheaths also increased.

This suggests that young CSF improves memory in aged mice by regulating oligodendrocytes.

Quantitative analysis of OPC and experimental pictures (the arrow in f indicates the proliferating OPC)

▲ Quantitative analysis of OPC and experimental pictures (the arrow in f indicates the proliferating OPC)

(YM-CSF represents the injected young CSF group, aCSF is the control)

To clarify the mechanism behind, the team further studied the signal transduction pathways activated by the cerebrospinal fluid of young mice.

The results showed that following infusion of young CSF, the most pronounced increase in gene expression wasserum response factor(SRF), which encodes a transcription factor that initiates cell proliferation and differentiation.

By infusing young cerebrospinal fluid into OPCs in a petri dish, the researchers found that after 6 hours, SRF expression returned to baseline levels and downstream targets associated with cell cycle and proliferation were upregulated.

Thus, experiments demonstrated that young CSF activated SRF channels in aged mice.

At the same time, the researchers also found that fibroblast growth factor FGF17 is a candidate factor for SRF signaling.

When FGF17 was added to the cerebrospinal fluid of normal aged mice, it was found to induce OPC proliferation and the mice had improved memory. And in OPCs treated with young cerebrospinal fluid, OPC proliferation was also affected when an inhibitor of FGF17 was added.

All of the above experiments point to FGF17 as a key target for restoring oligodendrocyte function in the aging brain.

Experts Miriam Zawadzki and Maria K. Lehtinen of Boston Children’s Hospital reviewed the study in Nature.

They say the research has implications for adding drugs to cerebrospinal fluid to treat diseases, especially those caused by aging.

In order to “return youth” to the brain, scientists have opened up their brains

The research was led by Professor Wyss-Coray.

He is an expert in neuroscience at Stanford University and graduated in 1992 with a Ph.D. in immunology from the University of Bernier, Switzerland. He leads the research direction of the laboratory mainly in brain aging and neurodegeneration, focusing on age-related cognitive decline and Alzheimer’s disease.

Previously, they found that when the blood of young mice was given to older mice, the latter’s brains revitalized, and the study was published in Nature Medicine. And found the protein VCAM1 that plays a key role in it. If the expression of VCAM1 is blocked, the learning and memory ability of old mice can be restored.

Later, Professor Wyss-Coray further discovered that,human cord bloodIt can also “rejuvenate” the brains of old mice.

Of course, in addition to the team of Professor Wyss-Coray, there are many scientists around the world who are open to the idea of ​​”returning youth” to the brain. Last year, a study in “Nature Aging” showed that,Microflora in transplanted fecescan also reverse the aging brain.

Researchers from the University of Ireland Cork said that by feeding old mice with microbes leached from their faeces, some of the immune changes that occur with aging were reversed in older mice.

These changes included an increase in immune cells in the peripheral blood, and microglia in the hippocampus returning to their youthful forms.

On the other hand, scientists at Boston University recruited 42 young people and 42 old people to conduct the experiment. They found that brief electrical brain stimulation may reverse some of the effects of aging in older brains.

One More Thing

It is worth mentioning that the related research of Professor Wyss-Coray inspired the previously controversialHuman exchange blood test. That’s the famous “Silicon Valley rich people change blood“.

In 2016, led by the American company Ambrosia, the world’s first clinical trial using young people’s blood to “treat” aging was launched. Ambrosia co-founder Karmazin said he was inspired to initiate the clinical trial by Professor Wyss-Coray’s research.

According to reports, at the time the study recruited a total of 600 volunteers over the age of 35, and the researchers would give each volunteer 1.5 liters of blood from healthy young adults over two days.Volunteers who come to participate in the trial also need to pay up to $8000The associated costs… Obviously a rich man’s game.

At that time, it was reported that Peter Thiel, a famous American entrepreneur and venture capitalist and co-founder of PayPal, showed great interest in this matter.

But having said that, this kind of “rejuvenation” research is indeed in the process of advancing, and it is indeed more likely to lead to ethical discussions.

What do you think about this?

Paper address:

https://www.nature.com/articles/s41586-022-04722-0

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