The main factor in brain longevity

(ORDO NEWS) — American biologists have found that the FOXO3 gene protects brain stem cells from aging. The research results are published in the journal Nature Communications.

Scientists know that many super-livers – people over 100 years old – share an unusual version of the gene for the Forkhead box O3 (FOXO3) protein. Now, researchers from Weill Cornell Medicine at Cornell University College of Medicine, along with colleagues at Duke University, have described how the gene affects the brain.

In 2018, Dr. Jihe Pike and her team discovered that brain cells in mice lacking the FOXO3 gene cannot cope with oxidative stress and die. In a new study, the authors found that FOXO3 supports the brain’s regenerative capacity by halting stem cell division until the environment is favorable for the survival of new neurons.

Problems with the vitality of brain cells can be associated with inflammation, radiation exposure, or nutritional deficiencies. All of these conditions put additional stress on the brain. But the biggest negative effect on brain cells is oxidative stress, in which harmful oxygen compounds accumulate in the body. It is this process that the authors studied.

“Stem cells make new brain cells that are essential for learning and remembering throughout life. If stem cells divide uncontrollably, they are depleted. The FOXO3 gene does its job by preventing stem cells from dividing until the stress passes.” researchers note.

Scientists have found that the FOXO3 protein is directly modified by oxidative stress, and this modification sends the protein into the stem cell nucleus, where it turns on the stress response genes.

The resulting reaction blocks a nutrient called s-adenosylmethionine (SAM), which a protein called lamina needs to form a protective sheath around DNA in the stem cell nucleus. As a result, DNA begins to leak out, the cell mistakes it for a viral infection, which triggers an immune response called a type I interferon response. One consequence of this response is that stem cells stop producing new neurons.

“Actually, this is very good, because at this time, the external environment is not at all ideal for newborn neurons. If new cells were in such stressful conditions, they would be killed. the stress won’t go away and then start producing neurons, ”explains Pike.

The research findings help explain why certain versions of the FOXO3 gene are associated with extremely long and healthy lives – they help people maintain a good supply of brain stem cells. But the authors warn that it is too early to talk about the possibility of creating new methods of rejuvenation and treatment of brain diseases.

“It can be a double-edged sword. Over-activation of FOXO3, if it happens all the time, can be very harmful,” the scientist warns.

The authors are now investigating how FOXO3 expression can be regulated and whether it can be briefly turned on and off.


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