Latest news with #DenaDubal
Yahoo
10-03-2025
- Health
- Yahoo
A Hidden Awakening in The Brain May Explain Why Females Age Slower
The 'silent' X chromosome within female brains may not be so silent after all. A new study has found evidence in both mice and humans that as we age, 'sleeping' X chromosomes can be 'awakened' in brain cells critical to learning and memory. The overlooked influence of this genetic library could be a key reason why females live longer than males and exhibit slower cognitive aging. "In typical aging, women have a brain that looks younger, with fewer cognitive deficits compared to men," explains neurologist Dena Dubal from the University of California, San Francisco (UCSF). "These results show that the silent X in females actually reawakens late in life, probably helping to slow cognitive decline." The X chromosome harbors about 5 percent of the human genome, and it is largely understudied in the aging brain, explain Dubal and her co-authors from UCSF, led by neurologist Margaret Gadek. Female mammals possess two X chromosomes - one from each parent – but in each cell of the body, a random one of those chromosomes is silenced and the other is activated. Some select genes from the X chromosome, however, can escape inactivation, and evidence suggests that as we grow older, more X chromosomes are not held down by genetic 'gag orders'. This means that the expression of both X chromosomes could potentially drive the different ways that male and female brains age. To test that idea, researchers investigated brain cells in the female hippocampus, which is a brain region strongly involved in learning, memory, and emotional processing. First, the team studied mice with X chromosomes from two different rodent 'strains', Mus musculus and M. castaneus. In their models, the X chromosome in M. musculus is missing an important gene, called Xist, which means it cannot be silenced like usual. This means in some of their offspring the M. castaneus X chromosome is always the one getting deactivated, so if its genetic effects show up in brain cells, then it is considered an "escapee". Using RNA sequencing, researchers looked at the nuclei of 40,000 hippocampal cells in four young and four old female mice to figure out which X chromosome is active. Readings that rose from the X were 91.7 percent M. musculus and 8.3 percent M. castaneus. Because the M. castaneus X chromosome was supposed to be silenced, this suggests between 3 and 7 percent of its genes somehow escaped inactivation. This was true of most cell types in the mouse hippocampus, and more so in older brains. The cells most likely to express genes of the inactive X include dentate gyrus neurons, which play a critical role in memory, and oligodendrocytes, which support the formation of neural connections. To see if these findings extend to human brains, researchers at UCSF looked through previously published data on inactive X genes that change with age in at least one or more types of brain cells. Around half of the aging-induced targets identified on the inactivated X chromosome caused human intellectual disability if mutated. This suggests that the inactivated X chromosome carries genes enriched for cognition-related factors. One of these genes, called PLP1, particularly increases its expression with age in the neurons, oligodendrocytes, and astrocytes of the dentate gyrus. The PLP1 gene expresses a protein involved in the formation of myelin sheaths that surround neurons and allow them to send messages more efficiently. "In parallel to mice, older women showed increased PLP1 expression in the parahippocampus, compared to older men," the authors explain. Increasing the expression of the PLP1 gene in male and female mice improved cognition in the aging brain, enhancing learning and memory in the animal models. This could be a possible target for future treatments of brain aging. "The study of female-specific biology is historically underrepresented in science and medicine but is essential and expanding fervently," the team concludes. "What X activation broadly means for women's brain health – or for other systems of the body – is now a critical area of investigation." The study was published in Science Advances. Men Have Higher Risk of Parkinson's, And We May Finally Know Why An Ancient Disease Has Reappeared in The US. This Could Be Why. Daylight Saving Disrupts Millions of Americans. There's a Better Way.
Yahoo
05-03-2025
- Health
- Yahoo
Mystery of why women age better than men may finally be solved
The mystery of why women age better than men may finally have been solved by scientists. Women tend to live about five years longer than men, and often avoid the severe mental decline and heart problems that plague the opposite sex. Now scientists have found that as women age, the silent unused 'X' sex chromosome wakes up and helps to protect the brain. Unlike men, women are born with two X chromosomes, but one switches off during the early stages of embryonic development. It was thought to be dormant throughout life, but a new study from the University of California has found that in ageing female mice, it reactivates and starts helping its twin to produce a critical brain protein that protects brain cells. Prof Dena Dubal, a specialist in ageing from UC San Francisco, said: 'We were astounded to find that ageing activated – or woke up – that silent X in the female brain in a brain region that's very important to learning and memory: the hippocampus. 'It's really fascinating that women live longer than men all over the world, and they also show less cognitive ageing. The biological clock of the female brain ticks a little slower than that of men's. 'Our work highlights reasons for resilience of the female brain in typical ageing.' Prof Dubal also said the discovery may have a wider impact. 'It may be a reason for sex differences in multiple degenerative diseases and conditions,' she added. 'We focused on one area of the brain, but what about the rest of the body and the inactive X chromosome? 'And what about cardiovascular disease and cancers? What role might this waking up of the X be playing in multiple organ systems and health and disease?' The team discovered that when the sleeping X chromosome reactivated, it triggered the production of the protein Plp1, a component in an important nerve shield called myelin. Myelin sheaths brain cells and allows information to flow between neurons, playing a big role in learning and memory. When experts further boosted the protein in the ageing mice, it improved their cognition, allowing them to explore and solve mazes, like younger mice. And it also worked in male mice. 'Even more surprisingly, this X factor Plp1 improved cognition in the male brain, highlighting that old brains are quite malleable and have the capacity for youthful function,' Prof Dubal said. 'So this is a clear example of how understanding female-specific biology can lead to new treatment for a female brain, as well as a male brain. Our research would suggest that we could all use a little more X.' The research was published in a special issue of the journal Science Advances, which was focused on women's health. In the edition, academics argued that medicine and science has historically overlooked the impact of sex, even though there are huge differences in biological processes in men and women. At a briefing launching the special edition, Dr Gillian Coughlan, a neurology specialist from Harvard Medical School, said: 'We know Alzheimer's disease does disproportionately affect women, and in contrast, Parkinson's disease disproportionately affects men. 'However, we know quite little really in understanding how sex biology, how hormones, how gender factors, can explain these sex differences in disease prevalence. 'And that's quite surprising. Because if we understood how these kinds of biological differences influence sex differences in disease prevalence, then surely that would go a long way to inform treatment, prevention and diagnosis.' Madeline Wood Alexander, a doctoral student at Sunnybrook Research Institute, University of Toronto, added: 'Again and again, we keep seeing female-specific and male-specific sex differences in the biology behind the diseases that affect us most as humans. 'To be a good scientist is to consider all of the factors that contribute to health and disease outcomes.' Broaden your horizons with award-winning British journalism. Try The Telegraph free for 1 month with unlimited access to our award-winning website, exclusive app, money-saving offers and more.
Observer
04-03-2025
- Health
- Observer
Why do women live longer than men?
Women outlive men by something of a long shot: In the United States, women have a life expectancy of about 80, compared with around 75 for men. This holds regardless of where women live, how much money they make, and many other factors. It's even true for most other mammals. 'It's a very robust phenomenon all over the world, totally conserved in sickness, during famines, during epidemics, even during times of starvation,' said Dr. Dena Dubal, a professor of neurology at the University of California, San Francisco. But the reasons women live longer are complicated and less established — and the fact that they are outliving men doesn't necessarily mean they are living better. Women tend to have shorter health spans (the number of healthy years a person lives) than men, said Bérénice Benayoun, an associate professor at the USC Leonard Davis School of Gerontology. Women are generally more physically frail than men in old age; they're also more vulnerable, particularly after menopause, to developing cardiovascular issues and Alzheimer's disease, in part because age itself is a risk factor for those conditions, Benayoun said. Scientists are trying to uncover the reasons men and women age differently in the hopes of extending the life span and health span for both. 'If we can understand what makes one sex more resilient or vulnerable, then we have new pathways, new molecular understanding, for new therapeutics that could help one or both sexes also be resilient,' Dubal said. Here's what they know so far about what causes the longevity gap. Genetics A growing body of research suggests that the XX set of female sex chromosomes (which, along with other chromosomes, carry our DNA) may impact longevity, though it's not clear exactly how. For example, a 2018 study conducted by Dubal's lab looked at genetically manipulated mice with different combinations of sex chromosomes and reproductive organs. Those with two X chromosomes and ovaries lived longest, followed by mice with two X chromosomes and testes. Mice with XY chromosomes had shorter life spans. 'There was something about the second X chromosome that was protecting the mice from dying earlier in life, even if they had testes,' Dubal said. 'What if there was something on that second X chromosome that was in some ways a sprinkle of the fountain of youth?' Scientists haven't yet examined this in humans, but Dubal said the fact that we have the same hormones and sex chromosomes and similar reproductive systems suggests that the findings could be similar in people. Epigenetic factors — environmental or lifestyle elements like climate or chronic stress that impact which genes are expressed, and how — may also play a role in life span, widening or shrinking the disparities between men and women, said Montserrat Anguera, an associate professor of biomedical sciences at the University of Pennsylvania School of Veterinary Medicine, who studies this topic. Hormones Researchers are also investigating the role of sex hormones like estrogen in longevity and are especially interested in the effect they have on the immune system. 'Decent data is showing that, at least before menopause, the female immune system tends to be better, more on it and better able to mount responses,' Benayoun said. In general, males 'tend to do much worse in response to infection,' which in turn could shorten their life spans; they're also more likely than women to die of sepsis, she said. One 2017 analysis found that women who experienced menopause later in life — older than 50 — lived longer than those who experienced it earlier. When estrogen levels drop, such as during menopause, women's immune systems seem to weaken. Women tend to catch up to (or surpass) men in terms of developing diseases that were less common before menopause, Benayoun said. Lifestyle and Behavior Behavioral patterns play a key role in the disparity. Women are generally less likely than men to smoke or drink heavily — behaviors that contribute significantly to mortality, said Kyle Bourassa, a psychologist and a senior fellow at the Center for the Study of Aging and Human Development at Duke University. Women also tend to practice more 'health-promoting behavior,' like wearing a seat belt or going to the doctor for annual checkups, Bourassa said. In addition, he said that women are more likely than men to socialize, protecting them from the detrimental effects of social isolation and loneliness. A 2023 analysis found they're also less likely to die by drug overdose or suicide. External Factors On a broader societal level, issues like war or gun violence disproportionately impact men, said Naoko Muramatsu, a professor of community health sciences at the University of Illinois Chicago. During the COVID pandemic, men died at higher rates than women. Research showed that they were more likely to hold jobs that exposed them to the virus, like food preparation or construction, or to be homeless or incarcerated, all of which affected mortality rates. Ultimately, it's a combination of all these factors that determines the life span gap, said Alan Cohen, an associate professor of environmental health sciences at Columbia University Mailman School of Public Health. 'There's probably a thousand ways that that's happening.' And even though we do have control over some factors, like drinking, smoking and diet, it's not yet clear how significantly longevity would be impacted by changing those behaviors, Bourassa said. 'We need randomized control trials to tease these things apart,' he said. This article originally appeared in
New York Times
25-02-2025
- Health
- New York Times
Why Do Women Live Longer Than Men?
Women outlive men, by something of a long shot: In the United States, women have a life expectancy of about 80, compared to around 75 for men. This holds true regardless of where women live, how much money they make and many other factors. It's even true for most other mammals. 'It's a very robust phenomenon all over the world, totally conserved in sickness, during famines, during epidemics, even during times of starvation,' said Dr. Dena Dubal, a professor of neurology at the University of California, San Francisco. But the reasons women live longer are complicated and less established — and the fact that they are outliving men doesn't necessarily mean they are living better. Women tend to have shorter health spans (the number of healthy years a person lives) than men, said Bérénice Benayoun, an associate professor at the U.S.C. Leonard Davis School of Gerontology. Women are generally more physically frail than men in old age; they're also more vulnerable, particularly after menopause, to developing cardiovascular issues and Alzheimer's disease, in part because age itself is a risk factor for those conditions, Dr. Benayoun said. Scientists are trying to uncover the reasons men and women age differently in the hopes of extending life span and health span for both. 'If we can understand what makes one sex more resilient or vulnerable, then we have new pathways, new molecular understanding, for new therapeutics that could help one or both sexes also be resilient,' Dr. Dubal said. Here's what they know so far about what causes the longevity gap. Genetics A growing body of research suggests that the XX set of female sex chromosomes (which, along with other chromosomes, carry our DNA) may impact longevity, though it's not clear exactly how. For example, a 2018 study conducted by Dr. Dubal's lab looked at genetically manipulated mice with different combinations of sex chromosomes and reproductive organs. Those with two X chromosomes and ovaries lived longest, followed by mice with two X chromosomes and testes. Mice with XY chromosomes had shorter life spans. 'There was something about the second X chromosome that was protecting the mice from dying earlier in life, even if they had testes,' Dr. Dubal said. 'What if there was something on that second X chromosome that was in some ways a sprinkle of the fountain of youth?' Scientists haven't yet examined this in humans, but Dr. Dubal said the fact that we have the same hormones and sex chromosomes, and similar reproductive systems, suggests that the findings could be similar in people. Epigenetic factors — environmental or lifestyle elements like climate or chronic stress that impact which genes are expressed, and how — may also play a role in life span, widening or shrinking the disparities between men and women, said Montserrat Anguera, an associate professor of biomedical sciences at the University of Pennsylvania School of Veterinary Medicine, who studies this topic. Hormones Researchers are also investigating the role of sex hormones like estrogen in longevity, and are especially interested in the effect they have on the immune system. 'There's decent data showing that, at least before menopause, the female immune system tends to be better, more on it and better able to mount responses,' Dr. Benayoun said. In general, males 'tend to do much worse in response to infection,' which in turn could shorten their life spans; they're also more likely than women to die of sepsis, she said. One 2017 analysis found that women who experienced menopause later in life — over age 50 — lived longer than those who experienced it earlier. When estrogen levels drop, such as during menopause, women's immune systems seem to weaken. And women tend to catch up to (or surpass) men in terms of developing diseases that were less common before menopause, Dr. Benayoun said. Lifestyle and Behavior Behavioral patterns play a key role in the disparity. Women are generally less likely than men to smoke or drink heavily — behaviors that contribute significantly to mortality, said Kyle Bourassa, a psychologist and a senior fellow at the Center for the Study of Aging and Human Development at Duke University. Women also tend to practice more 'health-promoting behavior,' like wearing a seatbelt or going to the doctor for annual checkups, Dr. Bourassa said. In addition, he said that women are more likely than men to socialize, protecting them from the detrimental effects of social isolation and loneliness. A 2023 analysis found they're also less likely to die by drug overdose or suicide. External Factors On a broader societal level, issues like war or gun violence disproportionately impact men, said Naoko Muramatsu, a professor of community health sciences at the University of Illinois Chicago. During the Covid pandemic, men died at higher rates than women. Research showed that they were more likely to hold jobs that exposed them to the virus, like food preparation or construction, or to be homeless or incarcerated, all of which affected mortality rates. Ultimately, it's a combination of all these factors that determines the life span gap, said Alan Cohen, an associate professor of environmental health sciences at Columbia University Mailman School of Public Health. 'There's probably a thousand ways that that's happening.' And even though we do have control over some factors, like drinking, smoking and diet, it's not yet clear how significantly longevity would be impacted by changing those behaviors, Dr. Bourassa said. 'We need randomized control trials to tease these things apart,' he said.
