Article summary: The cognitive resilience of older women

Silent X chromosome genes 'reawaken' in older females, perhaps boosting brain power, study finds

This is an excerpt from the above-titled article in Live Science. I highly recommend clicking through to read the whole thing!


Females have one active X chromosome and one dormant X chromosome in each cell. But a study suggests that genes on the dormant X get "reawakened" later in life, potentially giving the brain a boost.

Dormant genes on the X chromosome may reawaken in old age, potentially giving the aging female brain a boost that the male brain doesn't receive. This phenomenon may help to explain why, on many measures, females show a higher level of cognitive resilience in old age than males do.

There seem to be fundamental differences in how males and females age. When it comes to the brain, females have lower rates of various forms of dementia than males do, even though females live longer, on average. One exception is that females have higher rates of Alzheimer's disease than males do, although females with Alzheimer's tend to survive longer than males with the condition.

Males typically carry one X and one Y in each cell; they inherit the X from their mother and the Y from their father. Females, on the other hand, usually carry two X chromosomes — one from mom and one from dad. But each cell needs only one X to be active, so in females, the second X is "silenced," leaving only the maternal or paternal X switched on.

Among the 22 reawakened genes, one called PLP1 carries the instructions to make a key component of myelin, the fatty insulation that helps neurons send signals efficiently. It's known that mutations in PLP1 can decrease the amount of myelin in the brain, resulting in intellectual disability. It's also known that myelin can be compromised in aging and that loss of myelin function can contribute to cognitive decline.

To see if the reawakening of PLP1 might boost cognition, scientists confirmed that older female mice had more PLP1 activity in their hippocampi than the older male mice did. They artificially increased PLP1 using gene editing in both old males and old females found that both sexes performed better on tests of learning and memory after that boost.

To see if any of the findings extended to humans, the team looked at data previously collected for a large study of human brain tissue. Data weren't available for the hippocampus, but the brain tissue immediately surrounding the hippocampus showed more PLP1 activation in older women than in older men. So that hints that the same phenomenon might be unfolding in people.