New Study Finds the 'Silent' X Chromosome in Mice Activates with Age
Researchers believe this discovery may explain why females, including humans, tend to live longer and retain higher level of cognitive resilience in old age than males
Hiya!
Despite all we’ve learned about our shared external reality, we have no idea how much we don’t know. Often, anything we learn is a layer of an answer rather than the entire answer. Usually, we can only reveal one layer at a time before we’re forced to stop and put further investigations on a back burner.
Thanks to technological advancements, scientists can now re-examine previously halted research to discover even more. For instance, it’s commonly known that females predominantly have two X sex chromosomes. However, one is “active” while the other is “inactive,” and scientists weren’t sure why — but a recent study may reveal at least part of the answer.
Brain Differences Between the Sexes While Aging
Research indicates there’s a fundamental difference in how males and females age, especially when it comes to their brains.
Perhaps the most well-known difference is that females typically live longer than men, in every country worldwide, even during severe epidemics and famines. The life expectancy gap between males and females in the United States widened during the COVID-19 pandemic between 2019 and 2021, with men dying almost six years earlier than women.
However, females don’t just typically live longer than males; their quality of life, including their cognitive abilities, is generally better, too. For instance, females tend to have lower rates of dementia than males. Although there’s one exception, Alzheimer’s disease, which is about twice as common in females as males, even then, females with the disease still typically live longer than males who have it.
Scientists have long wondered why females generally age better and live longer. There are plenty of theories to explain it — from lifestyle habits and environmental factors, to differences in immune systems and hormones.
However, Margaret Gadek, an MD-PhD student at the University of California, San Francisco, recently co-led research I’ll tell you about soon, investigating what, if any, role the inactive X sex chromosome might play. She told Nicoletta Lanese of Live Science:
"There's been a lot of documented trends where there's resilience in cognitive aging in female populations, compared to males. There's a lot of excuses why these trends could be in place, but one thing we wanted to look into was the role of the X chromosome.”
After all, along with our hormones, our sex chromosomes are one of the most significant biological differences between males and females, so it makes sense they might explain the difference between males and females as we age.
The Sex Chromosomes
Humans and most (but not all) other mammals have two sex chromosomes, X and Y, that determine the sex of an individual, along with their external genitalia.
To be clear, a person’s sex is different than their gender, which is socially constructed, and their gender identity, which is a person’s deep, internal, and unique experience of gender, which may or may not correspond to their physiology or designated sex at birth.
Anyway, males typically have one X chromosome, which they get from their biological mother, and a Y chromosome from their biological father. Meanwhile, females usually have two X chromosomes, one from each biological parent.
However, some people are described as intersex because they have sex chromosomes and reproductive anatomy that differs from the typical definitions of female or male.
For instance, some people have XXY or just X sex chromosomes, and some people with XX chromosomes can have male testes, while people with XY chromosomes can have ovaries. So far, over 30 medical terms exist for specific combinations of intersex traits.
The X chromosome is particularly interesting to scientists, since it carries about 5 percent of the human genome. Another reason scientists are curious about the X chromosome because within the female body, only one is active while the other is silenced.
Adding to the mystery is that which one becomes activated or inactivated appears to be completely random. Further, once an X chromosome is inactivated, it will remain inactive throughout the person’s lifetime — or so scientists thought.
There are a couple of flaws in this system, however, that intrigued Gadek and her colleagues: Some genes on the inactive X chromosome resist the silencing process and remain active, and some inactive genes become active again as a person ages.
Rachel Buckley, an Associate Professor of neurology at Harvard Medical School who was not involved in the new study, explained to Lanese that,
"We simply haven't looked at the X chrom[osome] very much, and now we're starting to really shine a very, very big spotlight on it, and we're starting to realize things that we had not fully appreciated."
Gadek and her team grew curious about how these “reawakened” genes on the otherwise inactive X chromosome might affect brain aging, especially considering that the silencing effect is a uniquely female phenomenon. So, they conducted a study to find out.