Anti-aging: scientists find key proteins that make the brain "return to youth"
Posted: Jul 24, 2019
Infusing the blood of young mice into old mice will rejuvenate the brains of the latter. On the contrary, injecting the blood of old mice will reduce the cognitive ability of young mice. Tony Wyss-Coray, a professor of neurology at Stanford University, and his colleagues discovered these amazing phenomena a few years ago.
As soon as the results were published, widespread concern and many speculations were aroused. Is there any unknown factor in the blood that affects aging? People look forward to finding a key to eternal youth from the answers.
After several years of exploration, Professor Wyss-Coray led his research team to finally found a protein in blood, although not all possible factors have been identified yet. This protein is located in the aging path - the blood-brain barrier. Blocking the effect of this protein can not only counter the effects of aging blood, but also can make the brains of old mice "return to youth" without losing young blood! This result was recently published in Nature Medicine.
This protein, called vascular cell adhesion molecule 1 (VCAM1), is a protein that promotes the interaction between blood vessels and immune cells and is expressed in vascular endothelial cells. As a member of the immunoglobulin receptor family, VCAM1 binds to specific molecules on the surface of white blood cells. By analyzing the level of gene transcription, scientists found that when getting older, whether in humans or in mice, the expression of VCAM1 in the vascular endothelial cells of the brain is higher.
- As the age increases, the expression of VCAM1 increases
When the plasma of aged mice or the elderly is injected into young mice, the expression of VCAM1 in the vascular endothelial cells of young mice increases. At the same time, there are two physiological features associated with aging in the brains of young mice: fewer neonatal neurons in the hippocampus, and innate immune cells in the brain are activated.
These results suggest that VCAM1 is closely related to aging, but it does not explain whether VCAM1 is involved in the process of reducing brain’s cognitive ability by aging blood as a regulatory factor, or only that their increase is related to vascular inflammation.
- Young mice start "aging" in the brain after receiving the plasma of the elderly: the number of newborn neurons in the hippocampus is reduced
So, the researchers then tried to eliminate VCAM1 to see if it can offset the aging effects of aging blood. Interestingly, after applying antibodies to young mice to block VCAM1, or knocking out the Vcam1 gene in cerebral vascular endothelial cells, the researchers found that the plasma of aging individuals could no longer have the harmful effects to make brains age.
In view of the fact that VCAM1 is highly expressed in natural aging, the researchers then attempted to block VCAM1 directly in aging mice. After 3 weeks of antibody injection, the number of new neurons in the hippocampus of aged mice increased, and the inflammatory response of microglia decreased.
- Older mice were injected with antibodies to block VCAM1, and the number of new neurons in the hippocampus of the brain increased
In addition to the reversal of aging characteristics within the brain, the results of behavioral studies are even more surprising, further confirming that blocking VCAM1 has a significant effect on rejuvenating the brains of older mice.
The researchers designed a labyrinth experiment to test the memory of mice, in which animals needed to find a safe escape hole hidden on the table. 17-month-old mice spend more time, than younger mice who are 5 months old, to find the right place. However, when these older mice were injected with anti-VCAM1 antibodies every 3 days for a month, the speed at which they escaped was found to be as fast as the young mice! Another set of experiments on memory objects also showed that older mice had almost the same learning and memory abilities to younger mice after blocking VCAM1.
- Behavioral experiments showed that after blocking VCAM1, the learning and memory ability of old mice returned to the level of young mice
Blocking VCAM1 in the brain makes these mice smarter. This is what haven't been seen in the past years. But why does blocking of VCAM1 can reverse brain aging? Researchers put forward a hypothesis based on the existing results: in young mice, there is less VCAM1 on vascular endothelial cells, which causes microglia to divide and remain in a stable state, and continuously generate new neurons. In the aging brain, VCAM1 expression increased, binding more white blood cells to one side of the blood vessel and inhibiting neurogenesis.
However, when asked if it is possible to use VCAM1 as an anti-aging therapy, Wyss-Coray also cautioned that if VCAM1 antibodies are likely to be effective in Alzheimer's disease or other neurodegenerative diseases, then it is also necessary to pay attention to the potential risks. But undoubtedly, this discovery provides a promising target for the treatment of aging-related neurodegenerative diseases.
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