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A new study by researchers at the University of California, San Francisco (UCSF), using mice and human samples, found that as we age, “dormant” X chromosomes can “wake up” in brain cells involved in learning and memory.
The team, led by neurologist Margaret Hadeck, says this genetic mechanism has been underestimated. It may be a key reason why women tend to live longer than men and experience slower cognitive aging.
Neurologist Dena Dubal, a co-author of the study, said, “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.”
The X chromosome makes up about 5 percent of the human genome, but its role in brain aging has not been well studied.
What Did the Scientists Discover?
Female mammals have two X chromosomes—one inherited from each parent. In each cell, one of these chromosomes is randomly inactivated while the other remains active. Some genes on the X chromosome can escape that inactivation. The researchers found that with age, more X chromosomes stop being silenced by genetic “barriers.”
This means that expression from both X chromosomes could drive 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 examined the hippocampus in women. (The hippocampus plays an active role in learning, memory, and emotional processing.)
The researchers analyzed data from previous studies and found that the inactive X chromosome carries genes linked to cognition.
The scientists reported, “One of these genes, PLP1, particularly increases its expression with age in neurons, oligodendrocytes, and astrocytes of the dentate gyrus. The PLP1 gene encodes a protein involved in the formation of myelin sheaths that surround neurons and help them transmit signals more efficiently.”
In both female mice and older women, the authors reported, “there was increased expression of PLP1 in the parahippocampus compared to older men.”
“The study of female biology has historically been undervalued in science and medicine, but it is necessary and is now actively developing,” the researchers wrote. “The connection between X chromosome activation and the health of the female brain and other body systems is now a critical area of research.”
The results of the study were published in the journal Science Advances.
