A recent study investigates the impact of skewing towards the maternal X chromosome (Xm) versus X mosaicism (Xm+Xp) on organ functions and cognitive abilities in aging female mice.

The results indicated that mice with exclusively maternal X chromosomes exhibited poorer memory and accelerated aging in the hippocampus, a critical area for learning.

Dena Dubal, MD, Ph.D., the senior author of the study, warns that women with more active maternal X chromosomes might be at an increased risk for cognitive impairment and diseases like Alzheimer's as they age.

These findings enhance our understanding of the genetic factors contributing to 'inter-female' variation in cognitive abilities.

Published on January 22, 2025, in the journal Nature, the study may provide insights into sex differences in brain aging and the cognitive decline observed among women.

This research could illuminate the variations in age-related cognitive decline that are often seen in women.

The X chromosome houses genes essential for brain health, and mutations in these genes can lead to cognitive issues, as evidenced in conditions like Turner Syndrome.

The study emphasizes the significance of understanding X chromosome imprinting and gene expression in relation to cognitive aging and overall brain health.

The research raises intriguing questions about the evolutionary advantages of maternal X chromosome gene expression patterns that may support early brain development but contribute to cognitive decline later in life.

RNA sequencing revealed that nine genes were silenced or imprinted on the maternal X chromosome, potentially linking them to cognitive decline in aging females.

By using CRISPR technology to upregulate specific Xm-imprinted genes in the hippocampus, researchers improved cognitive functions in older female mice, counteracting some effects of cognitive aging.

Interestingly, the study found no significant differences in cardiac, bone, and metabolic functions between the Xm and Xm+Xp mice during middle age.