Aging: the XX advantage of women 🧬

Women possess two X chromosomes, one of which is usually "silent." This latter chromosome, long considered inactive in women, might actually play a crucial role in preserving cognitive abilities with age. Indeed, a recent study reveals that this chromosome reactivates later in life, offering unexpected brain resilience.


This discovery, made by researchers at the University of California, San Francisco (UCSF), opens new perspectives on sex differences in aging. By studying female mice, scientists observed that the "silent" X chromosome expresses genes beneficial to the brain at an advanced age, which could explain why women often retain their cognitive faculties longer than men.

The unexpected awakening of the X chromosome

Female mammals possess two X chromosomes, one of which is generally inactivated to avoid overproduction of proteins. This mechanism was previously considered a way to maintain genetic balance. However, this inactivation is not complete, and some genes manage to express themselves despite this imposed "silence."

In female mice aged 20 months (equivalent to 65-year-old humans), researchers observed that the inactive X chromosome begins to express around 20 genes. These genes, involved in brain development and cognition, appear to play a protective role in aging. This reactivation was particularly notable in the hippocampus, a key region for memory and learning.

The study used genetically modified mice to track gene expression on the inactive X chromosome. The results showed that this reactivation affects several types of brain cells, including neurons and oligodendrocytes. These findings suggest that the "silent" X chromosome could be an untapped genetic resource, contributing to the brain resilience observed in older women.

PLP1: a key gene for brain health

Among the genes reactivated on the inactive X chromosome, PLP1 particularly caught the researchers' attention. This gene plays an essential role in the production of myelin, a substance that insulates neuronal axons and improves nerve signal transmission. Myelin degradation is often associated with neurological disorders, making PLP1 important for brain health.

Older female mice showed higher levels of PLP1 in the hippocampus, a brain region essential for memory and learning. This increase suggests that the inactive X chromosome helps maintain the integrity of neural connections in aging females. Researchers also noted that older males had significantly lower levels of PLP1, which could partly explain their differences in cognitive resilience.

To test the impact of PLP1, scientists artificially increased its expression in older male and female mice. The results showed a notable improvement in cognitive performance, particularly in memory and learning tests. These observations pave the way for potential therapeutic interventions targeting PLP1 to slow age-related cognitive decline, both in women and men.