Beauty and brains that age slowly — turns out that women can have it all!
Men have an X and a Y chromosome, while women have two X chromosomes. Scientists have long dismissed one of the female X chromosomes as largely inactive, not doing much of anything.
A new study reports that this dormant chromosome actually awakens later in life and turns on genes that keep the brain healthy, which may be why women tend to retain their cognitive abilities longer than men.
Researchers from UC San Francisco discovered that when female genetically engineered mice reach the equivalent of about 65 human years, their “silent” X chromosome begins expressing genes that boost brain connections and increase cognition.
“In typical aging, women have a brain that looks younger, with fewer cognitive deficits compared to men,” said Dr. Dena Dubal, a UCSF professor of neurology. “These results show that the silent X in females actually reawakens late in life, probably helping to slow cognitive decline.”
Dubal’s team measured gene expression in the hippocampus, the brain structure responsible for learning and memory.
The researchers were stunned that the inactive X chromosome expressed about 20 genes in several cell types of the hippocampus. Many of the genes are involved in brain development and intellectual disability.
“Aging had awakened the sleeping X,” Dubal said.
“We immediately thought this might explain how women’s brains remain resilient in typical aging, because men wouldn’t have this extra X,” added Margaret Gadek, a UCSF graduate student and first author of the paper.
The UCSF researchers suspect PLP1 may be the key. The gene codes for the primary protein of myelin, which insulates nerve fibers in the brain and spinal cord.
Old female mice had more PLP1 in their hippocampus than old male mice. When the team artificially expressed PLP1 in the hippocampus of both sexes, the mice performed better on learning and memory tests.
An analysis of donated brain tissue from older men and women confirmed that only women had elevated PLP1.
The UCSF findings were published this week in the journal Science Advances.
Dubal and her colleagues are exploring whether the second X is active in older women and how this long-forgotten chromosome can rejuvenate aging brains.
“Cognition is one of our biggest biomedical problems, but things are changeable in the aging brain, and the X chromosome clearly can teach us what’s possible,” Dubal said. “Are there interventions that can amplify genes like PLP1 from the X chromosome to slow the decline — for both women and men — as we age?”