Researchers have discovered the existence of the FOXO3 gene which preserves the brain’s ability to regenerate by preventing the death of brain cells in the event of intense stress.
- The longevity gene called FOXO3 participates in the regeneration of brain stem cells by preventing them from dividing in the event of oxidative stress.
- This discovery could explain why long-lived people carry this gene, which preserves their brain stem cells.
What if the key to our brain’s longevity lies in a genetic variant? This was discovered by scientists from Weill Cornell Medicine in New York.
Based on previous work that showed many centenarians shared an unusual version of the Forkhead box protein O3 (FOXO3) gene, they wanted to study how this particular gene helps keep our brains healthy as we age. Their study has just been published in NatureCommunications.
Modification of FOXO3 by oxidative stress
The origins of this research start in 2018, when Dr. Jihye Paik and his team showed that mice that lack the FOXO3 gene in their brains are unable to cope with stressful conditions, leading to gradual death. brain cells.
This new study reveals the secret of FOXO3: it preserves the brain’s ability to regenerate by preventing stem cells from dividing until the environment favors the survival of new cells.
“Stem cells produce new brain cells, which are essential for learning and memory throughout our adult lives. explains Dr. Paik. If stem cells divide uncontrollably, they become exhausted. The FOXO3 gene seems to be doing its job by preventing stem cells from dividing until the stress has passed.”
As part of their research, scientists have mainly studied the reaction of brain stem cells when they are subjected to oxidative stress, a phenomenon of chemical oxidation that occurs when our cells are attacked by free radicals. They then found that the FOXO3 protein is directly modified by oxidative stress. “This modification sends the protein into the nucleus of the stem cell where it activates stress response genes”explains the researcher.
A survival response to stress
To cope with oxidative stress, brain stem cells then consume a nutrient called -adenosylmethionine (SAM). This nutrient is essential to help a protein called lamin form a protective envelope around DNA in the stem cell’s nucleus. “Without the SAM, the lamin cannot form this strong barrier and the DNA starts to leak out.”
A mechanical reaction of the stem cell follows which takes this DNA for a viral infection. It then triggers an immune response which puts it to sleep and stops the production of new neurons. “This response is actually very good for stem cells because the external environment is not ideal for new neurons, assures Dr. Paik. If the new cells were produced under such stressful conditions, they would be killed. It is better for stem cells to remain dormant and wait for the stress to subside to produce neurons.”
According to the researchers, these results could explain why, by helping to maintain a good supply of brain stem cells, certain versions of FOXO3 are linked to extraordinarily long and healthy lives. Boosting FOXO3 through regular exercise may also preserve mental alertness.
New work is now planned to investigate how FOXO3 is regulated and whether turning it on or off briefly would benefit health.
The longevity gene called FOXO participates in the regeneration of brain stem cells by preventing them from dividing in the event of oxidative stress.
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