Science
Aging Women’s Brain Mysteries Are Tested in Trio of Studies
Women’s brains are superior to men’s in at least in one respect — they age more slowly. And now, a group of researchers reports that they have found a gene in mice that rejuvenates female brains.
Humans have the same gene. The discovery suggests a possible way to help both women and men avoid cognitive declines in advanced age.
The study was published Wednesday in the journal Science Advances. The journal also published two other studies on women’s brains, one on the effect of hormone therapy on the brain and another on how age at the onset of menopause shapes the risk of getting Alzheimer’s disease.
A gene that slows brain aging
The evidence that women’s brains age more slowly than men’s seemed compelling.
Researchers, looking at the way the brain uses blood sugar, had already found that the brains of aging women are years younger, in metabolic terms, than the brains of aging men.
Other scientists, examining markings on DNA, found that female brains are a year or so younger than male brains.
And careful cognitive studies of healthy older people found that women had better memories and cognitive function than men of the same age.
Dr. Dena Dubal, a professor of neurology at the University of California, San Francisco, set out to understand why.
“We really wanted to know what could underlie this female resilience,” Dr. Dubal said. So she and her colleagues focused on the one factor that differentiates females and males: the X chromosome. Females have two X chromosomes; males have one X and one Y chromosome.
Early in pregnancy, one of the X chromosomes in females shuts down and its genes go nearly silent. But that silencing changes in aging, Dr. Dubal found.
She and her colleagues looked in the hippocampus, the brain’s center of memory and cognition, which deteriorates as one ages and is ravaged by Alzheimer’s.
When looking at aging hippocampuses, “we were astounded to find that genes woke up,” Dr. Dubal said, referring to the silent X chromosomes. The study was done in aging mice, but the researchers believe the finding is applicable to humans because mice show the same age-related effects on brain functioning, with females performing better than males.
Her group focused on one particular awakened gene, Plp1. It makes a protein that is part of myelin, a fatty sheath around nerve cells that “allows information to flow back and forth, like a highway,” Dr. Dubal said.
What would happen, she asked, if she used gene therapy to give aging male mice a dose of Plp1 in their hippocampuses?
Her team found that the mice regained memory and cognition. They did not even have to give the gene to many cells, Dr. Dubal added. “Just a little boost went a long way,” she said.
Then she gave the gene therapy to female mice, although they were already making Plp1. Their memories and cognition got even better.
“I’m so excited about this,” Dr. Dubal said. “Even an old brain can become more youthful and function better.”
Alzheimer’s and hormone therapy
Millions of women use hormone therapy to relieve symptoms of menopause like hot flashes and vaginal dryness, but there remains a concern about how it might affect the brain.
The issue was raised when a large and rigorous federal study, the Women’s Health Initiative, published in 2003, concluded that Prempro, a popular hormone treatment at the time, doubled the risk of dementia.
Since then, other scientists have argued that the risk depends on when a woman takes hormones. If she takes them within 10 years of menopause, they say, her brain will be fine. Current treatment guidelines reflect that view.
To examine what happens inside the brain after hormone therapy, Rachel F. Buckley, a neuroscientist at Massachusetts General Hospital, and her colleagues recruited 146 healthy women aged 51 to 89. They scanned the women’s brains for tau, a protein that accumulates in the brains of people with Alzheimer’s.
The investigators knew only the ages of the women, and whether they had ever taken hormone therapy. To Dr. Buckley’s surprise, they saw an effect.
The women over 70 who had received hormone therapy had a greater accumulation of tau than the women who had never had it. Having more tau did not mean the women had Alzheimer’s, but it could have put them on the path toward the disease.
Women under 70 in the study did not have more tau in their brains. But, the researchers said, they did not know if younger women who took hormones would have more tau later in life.
The study was observational, meaning it cannot prove cause and effect. The women with more tau might have been different in other ways that the researchers did not account for, which has left uncertainty about the finding.
Dr. Buckley, asked what advice she would give women about hormone therapy and the risk of Alzheimer’s, said “talk to your doctor,” acknowledging that it was not a satisfactory answer.
Age of menopause and Alzheimer’s
Another study published on Wednesday used clinical records and autopsy data to compare the brains of 268 women. Some started menopause early, around age 45, while the rest started at the more typical age of around 50.
The researchers who led the study reported that age at the start of menopause had no effect on cognitive decline, the integrity of brain synapses or on brain markers of Alzheimer’s.
The results, said Madeline Wood Alexander, the study’s lead author and a doctoral student at Sunnybrook Research Institute in Toronto, were “not what we expected.” The researchers thought the women who started menopause earlier would have worse brain functioning. That is because levels of estrogen, which can protect neurons, plummet at menopause, the authors said.
The researchers did identify one correlation that they emphasized as their main finding: The synapses of women who begin menopause earlier may become more vulnerable to changes linked to Alzheimer’s as they naturally deteriorate.
They reported that they did not see that effect in women with early menopause who used hormone therapy.
The result clashes with those of the other study, which indicated hormone therapy might increase the risk of Alzheimer’s-like changes in the brain. There was no clear explanation for the seemingly contradictory findings.
But experts not involved with either study questioned the conclusions about early menopause and hormone therapy. They said they were not convinced by the statistical analyses and modeling that led to this correlation.
Dr. Deborah Grady, emeritus professor of epidemiology and biostatistics at the University of California, San Francisco, said it was difficult to interpret studies that looked at things like the vulnerability of synapses. If menopause timing had an effect, she said, she’d like to see it show up in the actual incidence of Alzheimer’s in these women.
Dr. Jacques Rossouw, who was a program officer for the Women’s Health Initiative, had a similar concern. He added that the authors did so many statistical tests that it was possible the correlation they found occurred by chance.
And even if it is real, he said, “this can’t be a big effect if there was no effect of age of menopause on Alzheimer’s pathology.”
Science
China Launches Reusable Rocket in Race With SpaceX
Video released by Chinese state media shows a state-owned aerospace company launching a rocket and recovering part of it on Friday. The successful launch of a reusable rocket was a major step for China toward challenging SpaceX’s satellite internet dominance.
Science
Nobel Prize winner leaving UC Berkeley for new role in China
Nobel Prize recipient Omar Yaghi is leaving his role at UC Berkeley to lead the development of a new artificial intelligence institute at Tsinghua University in Beijing, the Chinese university announced.
Yaghi will head the AI Chemistry and Materials Research Institute at Tsinghua, where he was appointed an honorary professor in 2022. Known as AIMATRY (AI × Materials × Chemistry), the new center will focus on material design and synthesis through artificial intelligence, according to a statement from the university.
In 2025, Yaghi shared the Nobel Prize in chemistry with Susumu Kitagawa of Kyoto University and Richard Robson of the University of Melbourne for their development of metal-organic frameworks, a type of super-porous material in which metal ions and carbon-based molecules combine to form crystals with exceptionally large surface areas.
The material has the potential to combat climate change by capturing and storing carbon or other pollutants, and by extracting water from the atmosphere in water-scarce areas. Upon awarding the prize, a member of the Nobel committee likened the technology’s ability to store enormous amounts of stuff in seemingly compact spaces to Hermione Granger’s enchanted handbag in the Harry Potter series.
Yaghi’s Irvine-based company, Atoco, has said it will start taking orders later this year for its technology that harvests water from the air.
A representative for Yaghi said he was not yet available to respond to questions.
China is one of several countries that has been actively recruiting scientists from the U.S., where the Trump administration has slashed science funding, suspended research grants, fired science advisors and tightened immigration restrictions.
“For many, many years, our funding was very competitive; if you worked hard and you were doing good research, you would get funding,” Yaghi said of the U.S. in an interview with Scientific American earlier this year. “The current state is not so encouraging because of the cutting back on grants and support of science by the very agencies that many university researchers rely on.”
Yaghi was born in Jordan to Palestinian refugees, and immigrated to the U.S. when he was 15 to study.
“We’ve learned over and over in human civilization that scholars can move across borders,” Yaghi told the New York Times last year. “This is how knowledge spread and how vast regions of the world lifted themselves out of poverty.”
Science
Trump administration seeks to limit federal funding that doesn’t ‘advance’ presidential policies
A new rule proposed by the White House Office of Management and Budget would fundamentally overhaul the way federal grants are awarded and overseen — a sweeping change that one scientific society said “would all but end the use of scientific merit in the selection of grants and programs across the government.”
Proposed in late May, the rule would give political appointees unprecedented control over federal grants for research, education and infrastructure, and specifies that government funds can only be spent on projects “aligned with administration policies and priorities,” according to a copy of the proposed rule.
The rule would also restrict research topics, limit U.S. scientists’ ability to collaborate with colleagues in other countries and make it easier for the government to suspend or cancel grants at any time.
The changes are intended to improve “transparency, accountability, and oversight for Federal awards” while “ensuring that American tax dollars are not wasted or misused,” according to the White House office.
But critics say that if the rule is implemented, the final sign-off for grants will no longer be in the hands of subject-matter experts within individual agencies, but in those of political appointees.
“This touches all parts of American life,” said Dr. Eric Rafla-Yuan, a psychiatrist who practices at the Veterans Administration and San Diego County’s psychiatric hospital.
“Control of how all of the federal grants and programs are funded will fall under a small group of highly partisan individuals who would have very few limits on how they spend these billions of taxpayer dollars,” said Rafla-Yuan, who also chairs the Committee to Protect Public Mental Health advocacy group. “This touches everyone’s life, even if they don’t realize it.”
OMB published the proposed rule May 29, opening a 45-day comment period that closes July 13.
Opposition to the proposed rule has mobilized multiple sectors of society. Professional groups representing cancer researchers, civil engineers, county governments, medical schools, housing agencies, city and municipal governments, nonprofits and others have publicly expressed concerns about potential consequences.
By midday Thursday, the Federal Register logged nearly 100,000 comments about the proposal, many of them expressing concern.
“I understand the need for oversight, fiscal responsibility, and accountability. That is not the issue,” wrote Jack Feldman, a neuroscientist who holds the David Geffen School of Medicine Chair in Neuroscience at UCLA. “The issue is whether scientific research is to be judged by scientific merit, or whether it can be approved, denied, or terminated according to broad political criteria that may change from one administration to the next.”
Crucially, the rule converts policies governing federal grants from “guidance” into binding regulations that all agencies would be required to follow. It would give political appointees power to override federal agencies’ merit-based reviews and mandate that a political appointee review decisions to ensure that all awards “demonstrably advance the President’s policy priorities.”
The elevation of political appointees in what were previously merit-based decisions has alarmed many scientists.
“The proposed rule changes would all but end the use of scientific merit in the selection of grants and programs across the government,” read a statement from the Planetary Society, a nonprofit dedicated to space research.
Researchers and science groups have also expressed concern about a section of the rule prohibiting the promotion of “theories of disparate-impact liability” — a legal concept that refers to policies that appear neutral but cause disproportionate harm to certain groups.
The section’s vague language and many loopholes could have a chilling effect on any research that studies the effects of a disease, policy or public health intervention on any specific group of people, Rafla-Yuan said.
As an example, he said, “if there’s a specific age range that is at higher risk for suicide, and we want to figure out, well, what’s going on with people that are aged 14 to 19 … we can’t do that under the wording in this rule.”
New restrictions on collaborations with scientists in other countries would hinder opportunities for U.S. researchers and limit innovation, said Joanne Padrón Carney, chief government relations officer for the American Assn. for the Advancement of Science.
“Science is a global enterprise. Especially in biomedical and public health fields, diseases don’t care about borders or government policies,” she said.
California’s congressional delegation sent a letter Wednesday asking OMB to rescind the proposal, outlining concerns about its impact on scientific innovation, U.S. competitiveness and the fiscal stability of local governments, many of which rely on federal grants for local services.
The proposed rule grants the federal government broad powers to suspend or cancel grants for any reason, introducing “unprecedented unpredictability into local governance,” the lawmakers wrote, “leaving vital infrastructure projects unfinished and abandoning vulnerable populations who rely on these services.”
Republican Sen. Susan Collins has also asked the White House to withdraw certain parts of the letter and extend the public comment period, saying the proposed rule as written would “harm small and rural communities, undermine scientific and biomedical research, and conflict with Congress’ control over the federal funding process.”
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