A new study by researchers at the University of California, San Francisco (UCSF), conducted on mice and humans, has revealed that as we age, “dormant” X chromosomes can “wake up” in brain cells responsible for learning and memory.
The team, led by neurologist Margaret Hadeck, believes that this genetic mechanism has been underestimated by scientists in the past. However, it may be a key reason why women tend to live longer than men and exhibit slower cognitive aging.
“In typical aging, women’s brains appear younger, and they experience fewer cognitive impairments compared to men. The results suggest that the silent X chromosome awakens in women later in life, likely helping to slow down the decline in cognitive abilities,” noted neurologist Dena Dubal, a co-author of the study.
According to the researchers, the X chromosome makes up about 5 percent of the human genome, but its role in brain aging has not been sufficiently studied.
What Did the Scientists Discover?
Female mammals have two X chromosomes—one inherited from each parent. However, in each cell of the body, one of these chromosomes is randomly suppressed while the other is activated. Some selected genes on the X chromosome can escape inactivation. The researchers found that as we age, an increasing number of X chromosomes are not held back by genetic “barriers.”
This means that the expression of both X chromosomes potentially drives different brain aging processes in men and women, according to Science Alert.
To reach this conclusion, the team studied the hippocampal cells of female mice and then tested their theory on the hippocampus of women. (It’s worth noting that this area of the brain plays an active role in learning, memory, and emotional processing.)
The researchers analyzed data from previous studies and discovered that the inactive X chromosome carries genes enriched with factors related to cognition.
The scientists confirmed: “One of these genes, PLP1, particularly increases its expression with age in neurons, oligodendrocytes, and astrocytes of the dentate gyrus. The PLP1 gene expresses a protein involved in the formation of myelin sheaths that surround neurons and help them send messages more efficiently.”
In both female mice and older women, “there was increased expression of PLP1 in the parahippocampus compared to older men,” the authors reported.
“The study of female biology has historically been undervalued in science and medicine, but it is necessary and is now actively developing,” the researchers noted. “The connection between X chromosome activation and the health of the female brain and other body systems is now a critical area of research,” they added.
The results of the study were published in the journal Science Advances.