CRISPR gives murine brain stem cells a youthful appearance. Disambling a metabolism-related gene restores cells’ capacity to produce new neurons. Using CRISPR gene editing on mice has shown clues to maintaining the brain’s regenerative cells young and active into old age (1). The scientists of this study discovered that decreasing the activity of a particular gene revitalized the brain’s stem cells, enabling them to proliferate and provide the brain with new neurons. Age hinders the brain’s stem cells’ capacity to produce new cells. That gene regulates how much glucose, a carbohydrate essential to cellular metabolism, is consumed by stem cells. An emerging picture from research on postmortem human brains is consistent with these mouse data. It has been showed that age affects metabolism in the brain as published in Nature (2). The role of neural stem cells in the adult human brain has been controversial. There is a published evidence that new neurons are made in the hippocampus, a region of the brain that is important for learning and memory, at least until the age of 79 (2), although, some researchers have reported that they could not find evidence that adults make new neurons in the hippocampus. On the other hand, in mice, the picture is clearer and it is known that neural stem cells in a brain region called the subventricular zone can give rise to neurons and other cell types. These newborn cells then migrate to the olfactory bulb, which controls the sense of smell (3). However, these stem cells become less active as mice get older. In this work (3), researchers methodically disrupted 23,000 genes using CRISPR–Cas9 genome editing, then examined the impact of each gene disruption on neural stem cells isolated from young and old mice and grown in a lab. The screen yielded 300 genes that may contribute to the aging of neural stem cells. By utilizing CRISPR-Cas9 to damage some of these genes in cells in the subventricular zone of living young and elderly mice, the researchers were able to further restrict the pool. After examining the animals’ olfactory bulbs, the authors discovered a small group of important genes. When these genes were disrupted, stem cells in older animals produced more neurons; however, young animals’ stem cells were unaffected. One such gene, Slc2a4, produces a protein that allows cells to absorb glucose. When it was disrupted, cells consumed less glucose and had more capacity to proliferate. These results are consistent with earlier research that linked sugar metabolism to aging. For instance, a diabetes medication has been shown to prevent age-related cognitive deterioration in monkeys (4).
The findings offer crucial information for the development of cell therapies that could one day treat neurodegenerative diseases, even if the role of brain stem cells in adult human is debatable.