How longevity gene protects brain stem cells from stress

A gene linked to unusually long lifespans in humans protects brain stem cells from the harmful effects of stress, according to a new study.

According to the researchers, studies of humans who live longer than 100 years have shown that many share an unusual version of a gene called Forkhead box protein O3 (FOXO3).

The study showed that mice that lack the FOXO3 gene in their brain are unable to cope with stressful conditions in the brain, which leads to the progressive death of brain cells. The gene preserves the brain's ability to regenerate by preventing stem cells from dividing until the environment will support the new cells' survival.

"Stem cells produce new brain cells, which are essential for learning and memory throughout our adult lives," said lead author Paik, Associate Professor at the Cornell University in the US.

"If stem cells divide without control, they get depleted. The FOXO3 gene appears to do its job by stopping the stem cells from dividing until after the stress has passed," Paik added.

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Many challenges like inflammation, radiation or a lack of adequate nutrients can stress the brain. But the team looked specifically at what happens when brain stem cells are exposed to oxidative stress, which occurs when harmful types of oxygen build-up in the body.

"We learned that the FOXO3 protein is directly modified by oxidative stress," she said. This modification sends the protein into the nucleus of the stem cell where it turns on stress response genes.

The resulting stress response leads to the depletion of a nutrient called s-adenosylmethionine (SAM). This nutrient is needed to help a protein called lamin form a protective envelope around the DNA in the nucleus of the stem cell.

"Without SAM, lamin can't form this strong barrier and DNA starts leaking out," she said.

The cell mistakes this DNA for a virus infection, which triggers an immune response called the type-I interferon response. This causes the stem cell to go dormant and stop producing new neurons.