Inactive genes on the X chromosome can go back to old age, possibly an aging female brain can promote a boost that the male does not receive the brain.
This phenomenon can help explain why, on many measures, women show high level of cognitive flexibility in old age than men.
Conclusions come from a new study in laboratory mice, and researchers also supported results with genetic data from humans. More research still needs to be confirmed that conclusions in mice translate people, but overall, the work indicates a possible difference in the age of female and male brain.
Historically, “We have not seen just X Chrome (Osom) too much,” Rachel BakleAn Associate Professor of Neurology at Harvard Medical School who was not involved in the new study. “And now we are really a very large, very big spotlight shining on it, and we are starting to feel the things we did not fully appreciate” – ie, how sex Chromosome This can affect how the brain is age.
Bakle told Live Science, “There are very important and potential therapeutic goals that are coming out of these letters” who focus on the X chromosome, Bakle told Live Science.
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Female brain flexibility
There are fundamental differences in the age of men and women. When it comes to the brain, the rate of women is low Different forms of dementia Compared to men, even if Women last longon average. An exception is that the rate of women is higher Alzheimer’s disease Compared to men, however Women live long with Alzheimer’s Compared to men with condition.
“There are lots of documented trends where there is flexibility in cognitive aging in the female population compared to men,” said the first author of the study. Margaret GadakAn MD-PHD student at the University of California, San Francisco. “There are many reasons why these trends can be, but one thing we wanted to see was the role of X chromosome,” Gedec told Live Science.
With hormones, sex chromosomes – X and Y – are one of the most spectacular biological differences among men and women, and they can help provide biological explanations as to why these intercourse emerges in the age aging.
Men usually carry an x and a y in each cell; He is inherited from his mother and is a Y to his father. On the other hand, women usually carry two xs Chromosome – From a mother and one from a father. But each cell requires only one X to be activated, so in women, the other X is “silenced,” is left only to the maternal or ancestral X.
This is not a spontaneous process. Some genes on the silent X chromosome avoid that silenting process, and thus Switched onWhereas Additional genes can switch back As a person’s age. Gedac and his colleagues wondered how these “re -acquired” genes could be factors in brain aging, especially given that this silenceing is a specific female phenomenon.
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Nearly two dozen “Received” genes
In his new study, published in the journal on 5 March Science progressResearchers crossed two sub -species of laboratory mice – called Mus musculus And Musk Castenus – So that the offspring of each rodent inherited from the pre -sub -species to one X and later. The team genetically held mice in such a way that X to X M. Castenus Was always silent. Generally, each cell has a silent X random.
This practical setup made it easy to mention which chromosome was related to an active gene and therefore, whether it was “escaped” the silenting process, Gedec explained.
With its modified mice in hand, the team then examined the gene activity in four young mice and four old mice, of which the later were 20 months old. (It is about 65 in human years.)
They zoom on gene activity in particular cells Sea horseA major memory center in the brain that shrinks with normal aging and cognitive decline and is greatly affected in dementia. He saw over 40,000 cells in total, including neurons and a variety of glial cells, which help maintain and support neurons in the brain and also create an insulating substance, called myelin.
This analysis showed that, with age, about 22 genes that were initially silent, switched back. GADEC stated that only a few genes were re -placed in many mice, while others were more variable.
“I was really surprised to see that we could think of ex-related inactivity migrationism as a ceremony of age,” said Bakle. “So as women get older, there will be more”-which means ex-linked gene activity- “and in fact it’s something quite protective,” she said.
Importance of insulation in the brain
One in 22 genes, called one Plp1 Gedec said that the part jumped as interesting as it was switched in seven of the nine cell types studied.
The PLP1 bears the instructions to create a major component of myelin, with fatty insulation that helps neurons to send signs efficiently. It is known that mutation in PLP1 can reduce the amount of myelin in the brain, A result of intellectual disabilityIt is also known that melin can Aging And loss of myelin function can contribute to cognitive decline.
To see if PLP1’s re -awakening could promote the feeling, scientists made some experiments with male and female mice. In one, he confirmed that old female mice had more PLP 1 activity in their hippocampi, compared to old male mice. In the second experiment, researchers artificially used PLP1 Gene editing In both old men and old women, and they found that both sexes performed better on learning and memory tests after that boost.
To see if no conclusions have been expanded to humans, the team saw the data collected earlier for a large study of the human brain tissues. Data were not available for hippocampus, but the brain tissue around the hippocampus showed more PLP1 activation in older women than older women. So that the same incident can be revealed in people.
Gedec said that, in the future, she is interested in seeing this re -obtained gene in the animal model of diseases like dementia, as the current mouse experiments only saw healthy aging. Bakle said that it would also be interesting to investigate the incident in the context of menopause.
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In menopause, estrogen levels fall. There are several functions in the brain of the hormone, which involves helping shuttle fuel from blood in brain cells. Bakle pointed to research under the leadership of a neuroscientist Robert Binton At the University of Erizona, which suggests, such as estrogen levels fall, brain may break some of their own mayaline for fuel.
In reading new studies, Bakle added dots and wondered whether the promotion of myelin in later life could be a way to overcome the first hit taken during menopause. “This is something that really sat down to me,” he said, although the idea is betting for now.
The current study was mainly in mice, Bakle noticed that it requires more work to see how this phenomenon comes up in the human brain. And in the long term, it will affect scientists to study the role of Y chromosome in brain aging; Although it takes much less genes compared to X, it can still have an effect, he said.
“One thing is that this letter has been highlighted that studying sex chromosomes is not a top woman’s health issue,” Gedec said. “It provides cognitive aging and certainly an insight into other areas of health that can benefit men and women and all equally, as we all have an X chromosome.”
