Nat Commun: Longevity gene FOXO3 protects neural stem cells in the brain from stress mechanisms

News February 23, 2021/bioon.
com" target="_blank">/---In a new study, researchers from the Weill Cornell Medical College in the United States discovered that a gene FOXO3 related to the prolonged lifespan of humans can protect the neural stem/progenitor cells in the brain (Neural stem/progenitor cell, NSPC) is protected from the harmful effects of stress.
Related research results were recently published in the journal Nature Communications, with the title of the paper "Cellular stress signaling activates type-I IFN response through FOXO3-regulated lamin posttranslational modification".

Picture from Nature Communications, 2021, doi:10.

Research on people who live over 100 years old shows that many people have an unusual version of the FOXO3 gene.
This discovery prompted Dr.
Jihye Paik, associate professor of pathology and laboratory medicine at Weill Cornell Medical College, and her colleagues to study how this gene promotes brain health during aging.

In 2018, Dr.
Paik and her team have discovered that mice lacking the FOXO3 gene in their brains cannot cope with the stress in the brain, which causes their brain cells to gradually die.
In this new study, they revealed that FOXO3 prevents NSPC from dividing until the environment supports the survival of newly created cells, thereby preserving the brain's ability to regenerate.

Dr.
Paik said, "NSPC produces new brain cells, which are essential for our learning and memory throughout our adult life.
If NSPC divides uncontrollably, they will be consumed.
The function of the FOXO3 gene appears to be to prevent NSPC.
Split until the stress disappears.
"

Many challenges, such as inflammation, radiation, or lack of adequate nutrients, can stress the brain.
But Dr.
Paik and her colleagues specifically studied what happens when NSPC is exposed to oxidative stress, which occurs when harmful types of oxygen accumulate in the body.

She said, "We learned that oxidative stress directly modifies the FOXO3 protein.
This modification sends this protein into the nucleus of the NSPC, where it turns on the stress response genes.
"

The resulting stress response leads to the consumption of a nutrient called S-adenosylmethionine (SAM).
This nutrient is used to help a protein called lamin (lamin) form a protective film around the DNA in the nucleus of NSPC cells.
She said, "Without SAM, lamin cannot form such a strong barrier, and DNA will begin to leak out.
"

The NSPC mistakes this DNA for a viral infection, which triggers an immune response called a type I interferon response.
This causes the NSPC to enter a dormant state and stop producing new neurons.

Dr.
Paik explained, “This response is actually very beneficial to NSPC, because the external environment is not ideal for newly born neurons.
If new cells are created under such stress conditions, they will be killed.
.
For NSPC, it’s best to stay dormant and wait until the stress disappears before generating neurons.
"

This research may help explain why certain versions of FOXO3 are associated with long healthy lifespans---they may help people maintain good NSPC reserves.
This may also help explain why regular exercise that enhances the activity of FOXO3 helps maintain mental sharpness.
However, Dr.
Paik cautioned that it is too early to know whether this new information can be used to develop new treatments for brain diseases.

Dr.
Paik explained, “This may be a double-edged sword.
Excessive activation of FOXO3 can be very harmful.
We don’t want to keep it on all the time.
”

To better understand the process, she and her colleagues will continue to study how FOXO3 is regulated and whether it is beneficial to health if it is turned on or off briefly.
(Bioon.
com)

References: 1.