In recent years, the CRISPR gene editing technique has proven to be a very useful tool, with positive results in hearing problems, treating blindness, or treating HIV, among others. Now, the use of this technique has made it possible to obtain clues to keep regenerative brain cells young and energetic into old age.
Age prevents brain stem cells from producing new cells, but a recent study published in Nature indicates that reducing the activity of a particular gene rejuvenates these stem cells, allowing them to proliferate and provide the brain with a supply of new neurons.
That particular gene regulates glucose consumption by stem cellsa key sugar for cellular metabolism. The results obtained in mice fit well with an emerging picture from studies of human brains post mortem.
These studies have also found that age affects brain metabolism. Both the results in humans and the study in mice “open new avenues for possible therapies,” the study notes.
The role of neural stem cells in the adult human brain has been controversial. Previous studies have shown that new neurons are created in the hippocampus, a region of the brain that is important for learning and memory, at least until the age of 79.
While in humans the evidence linked to the ability to create new neurons is controversial, in mice, the picture is clearer. Neural stem cells in a region of the brain called the subventricular zone They can give rise to neurons and other types of cells. These young cells then migrate to the olfactory bulb, which controls the sense of smell.
“A constant supply of new neurons to the olfactory bulb makes sense in mice, because They rely heavily on smell to perceive changes in their environment”explains Anne Brunet, geneticist and co-author of the study.
However, as the mice age, those stem cells become less active. Brunet’s team set the goal of trying to find the reason. To do this, they used CRISPR, a tool that allowed them to systematically alter 23,000 genesand then tested the effect of each altered gene in neural stem cells that had been taken from young and old mice and grown in the laboratory.
The analysis pinpointed 300 genes that could play a role in the aging of neural stem cells. The researchers narrowed the group down further by using CRISPR to alter some of them in cells from the subventricular zone of living young and old mice. They then combed through the animals’ olfactory bulbs and identified a select group of key genes. The alteration of These genes increased the production of neurons by stem cells in old animals, but did not affect stem cells in young animals.
One of these genes, called Slc2a4, encodes a protein that imports glucose into cells. By altering it, The glucose intake of the cells was reduced and their proliferation capacity was increased.
That result is consistent with previous studies that have found a link between sugar metabolism and aging. For example, a diabetes drug can prevent age-related cognitive decline in monkeys. But the latest finding is particularly important, he says, because points to a specific protein that has a key role and could be the target of future studies.
“Even if the role of neural stem cells in adult humans is in doubt, the results provide crucial information for the design of cell therapies that could one day treat neurodegenerative diseases,” the study concludes.