What's in a number, when it comes to age?
Adult female brains appear, on average, a few years younger than same-aged male brains, a new study finds. This suggests that sex affects how our brains age, which in turn might influence our tendency to develop neurodegenerative diseases such as Alzheimer's, according to research published Monday in the journal Proceedings of the National Academy of Sciences of the United States.
"We don't see brain aging itself as something that needs to be 'halted'," Dr. Manu S. Goyal, lead author of the study and an assistant professor of radiology and neurology at Washington University in St. Louis, wrote in an email.
It's the diseases that come with brain aging that are the problem, he said: "So what we need to understand is how brain aging contributes to diseases such as Alzheimer's disease, and why some people are more or less resilient to developing Alzheimer's and other brain diseases."
How effectively our brains burn fuel is part of brain aging
The brain may make up just 2% of our total body mass, but it uses a quarter of our body's total glucose. As we grow older, we experience a decline in brain metabolism, the brain's ability to convert circulating glucose into fuel. Brain cells metabolize glucose to produce the energy needed to maintain synaptic functions and perform other cellular tasks.
Scientists have seen a variety of sex differences in the brain, including stress response, some gene expression and disease. Theorists have predicted that females, generally, might have more youthful brains than males, Goyal and his colleagues note, but until now, scientists seeking to test that have focused on postmortem brain analyses, and their results have been contradictory.
For the new study, the researchers analyzed PET scans of 205 adults, all cognitively normal. Each person had five or six brain scans, which, combined, showed measurements of regional glucose use, oxygen consumption and blood flow in the brain.
"We used a 'machine learning' technique to 'guess' at how old each of our study participants was based only on their brain metabolism," Goyal explained. "We found that the technique 'guessed' quite well, but often predicted a person's age to be more or less than their actual age."
Did sex affect brain age? Here, Goyal and his colleagues compared participants' actual ages with their metabolic brain ages to see whether each brain was younger or older than expected.
"We found that the machine learning technique typically guessed a slightly younger age for women than their actual age," he said. The team performed a variety of calculations and analyses that showed different results, though the overall result was the same: Female brains were determined to be metabolically younger than their chronological age, though this difference between actual age and metabolic age was "relatively small," Goyal said. This variance was seen across all participants, who ranged in age from 20 to 82.
"What this tells us is that sex has an effect on how the brain ages, metabolically speaking," he said.
Goyal and his co-authors explained that their findings are consistent with evidence from previous studies indicating that, compared with the male brain, the female brain displays less cerebral blood flow loss after puberty, more brain glycolysis (or breaking down of glucose) in young adulthood and decreased loss of certain types of cerebral gene expression over time.
Combined, past and present findings suggest that the female brain is more youthful beginning in young adulthood and that this persists throughout her life. Sex differences during brain development, then, might set the stage for the overall trajectory of brain aging.
Understanding brain age is important to understanding disease
Samuel Neal Lockhart, an assistant professor of gerontology and geriatric medicine at Wake Forest School of Medicine, wrote in an email that the size and scope of this new study is one of its strengths.
"This immense amount of data" allowed the researchers "to convincingly show that, no matter how you look at it, males have more accelerated metabolic brain age (e.g., greater than their actual calendar age)," said Lockhart, who was not involved in the new study but who has researched the roles of vascular and metabolic disorders in the onset and progression of Alzheimer's disease.
"We are interested in results like those presented here, because they not only help us to understand how factors like sex contribute to different trajectories of metabolic brain health in late life, but also help us to understand the potential causes and early signs of Alzheimer's Disease," Lockhart said. Early diagnosis and intervention could improve quality of life and potentially slow the course of disease, he said.
Still, he noted that people "can make lifestyle choices today to positively impact their brain and cognitive health," including eating a nutritious diet and increasing physical activity.
Goyal and his colleagues hypothesize that the greater youthfulness in the female brain might provide some degree of resilience to aging-related changes. Still, more research is needed to better understand brain aging overall and to help prevent or delay neurodegenerative diseases, including Alzheimer's, which are "a major growing problem in the United States and elsewhere," he said.
"Certainly, diet and exercise might be part of the equation here and we and others are planning to study this and how body metabolism in general influences brain metabolism in healthy aging and in disease," he said.
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