A new study has found that the X chromosome passed down to the child from the mother might be responsible for accelerated brain ageing, potentially increasing the risk of conditions like Alzheimer’s disease. Only females have two X chromosomes (XX) while males have one X and one Y (XY). Given the natural order, the X chromosome carries a significant amount of genetic material, and any mutation or variation here can have profound effects, especially as one X chromosome in females is randomly inactivated in each cell.
Though women tend to live longer than men and have lower rates of dementia, one exception is Alzheimer’s disease which affects them at higher rates. Even then, some studies suggest that females survive longer with Alzheimer’s than males do. The researchers set out to find the reason and believed that the sex chromosomes, X and Y, could help explain the differences.
“Skewing of the X chromosome is common among humans, and there are certainly women who are walking around with much higher or lower levels of maternal X chromosomes than others, just by chance,” said Dena Dubal, senior author of the paper.
“There has been little research on the potential consequences of this,” she added.
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‘The experiment’
To further explore the idea, the researchers experimented with female lab mice of different ages. In some cases, the paternal X chromosomes were silenced, leaving only the mother’s X active. These mice were compared with others that had a mix of maternal and paternal X’s switched on.
As per the findings, the young “Mom-X” mice were cognitively similar to young mice but the older ones showed steep cognitive decline. In the brains of these mice, the maternal X chromosome sped up biological ageing in the hippocampus – a brain area crucial for learning and memory.
“These findings raise the possibility that some women who express more of their mom’s X chromosome just by pure chance may have more cognitive impairment with aging or an increased risk for diseases like Alzheimer’s,” said Ms Dubal.
“Ultimately, it could also help us find constructive strategies for slowing brain aging in both sexes.”
Though the research was conducted on mice, the findings, if they translate to humans, could point to drivers of cognitive decline related to a particular sex and, eventually, help us fund ways to prevent or treat them.
