Women have a brain aging advantage men don't-the silent X chromosome - Silicon Canals

"For decades, scientists have observed a consistent pattern: women typically live about five years longer than men and exhibit slower cognitive decline as they age. Now, groundbreaking research from the University of California, San Francisco has uncovered a surprising biological mechanism that may explain this disparity. The discovery centers on what researchers once dismissed as a dormant structure, the so-called "silent" X chromosome that exists in every female cell."

"However, research published in Science Advances reveals that this understanding requires significant revision. Dr. Dena Dubal and her team at UCSF discovered that in aging female mice, equivalent to approximately 65-year-old humans, the supposedly silent X chromosome begins expressing over 20 genes. These newly activated genes predominantly appear in the hippocampus, the brain region crucial for learning and memory that typically deteriorates with age."

"The research employed advanced single-nucleus RNA sequencing to profile more than 40,000 nuclei from young and old female mouse brains, revealing patterns of gene reactivation that had gone undetected for decades. The PLP1 protein makes a measurable difference Among the genes escaping silencing, one particular candidate stood out to researchers: PLP1. This gene helps construct myelin, the fatty insulation surrounding neural pathways that enables efficient signal transmission throughout the brain."

Women typically live about five years longer than men and show slower cognitive decline with age. A previously considered silent X chromosome in female mammals begins expressing over 20 genes in aged female mice, especially in the hippocampus. Single-nucleus RNA sequencing of more than 40,000 nuclei from young and old female mouse brains revealed gene reactivation patterns previously undetected. Among escaping genes, PLP1, which supports myelin formation, shows significantly higher hippocampal levels in old females than in old males, implying additional myelin production from the second X. These changes offer a biological mechanism for sex differences in aging and cognition.

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