Female brains remain youthful as male brains wither, study suggests

Fiza Pirani
The Atlanta Journal-Constitution

Why do women tend to stay “mentally sharp” in their later years? According to researchers at the Washington University School of Medicine, it may be that women’s brains shrink slower with age compared to men’s brains.

The university’s new study, published in the Proceedings of the National Academy of Sciences, suggests women’s brains appear to be about three years younger than the brains of their male counterparts of the same chronological age.

“We’re just starting to understand how various sex-related factors might affect the trajectory of brain aging and how that might influence the vulnerability of the brain to neurodegenerative diseases,” senior author Manu Goyal, an assistant professor of radiology at the university’s Mallinckrodt Institute of Radiology said in a news release. “Brain metabolism might help us understand some of the differences we see between men and women as they age.”

The researchers note “this study cannot separate the effects of sex — a biologically determined characteristic — from gender, which includes societal influences.”

Sugar: To better understand metabolism differences between the sexes, Goyal and his team studied 205 people — 121 females and 84 males ages 20-82 — all of whom underwent PET brain scans to measure the flow of oxygen and glucose (or sugar) in their brains.

Why sugar? Well, as we age, how the brain runs on sugar changes. For example, brains of infants and children run on sugar through a process called aerobic glycolysis, which “sustains brain development and maturation,” according to researchers. The remaining sugar is used for thinking and other daily tasks. By the time we reach our 60s, our brain is spending very little sugar fuel on aerobic glycolysis.

By examining participants’ PET scans, researchers were able to determine the fraction of sugar devoted to aerobic glycolysis in multiple regions of the brain.

Next, they trained a machine-learning algorithm to find the relationship between age and brain metabolism by feeding it the participants’ ages and brain metabolism data. When the algorithm calculated a female’s brain age from its metabolism, the algorithm yielded an average brain age 3.8 years younger than her chronological age. The algorithm found male’s brains, on the other hand, were 2.4 years older than their actual ages.

Results: These results suggest that female brain neoteny (or the appearance that it’s more youthful than the male brain) persists throughout adulthood — and demonstrates “sex differences during brain development set the stage for subsequent trajectories of brain aging,” authors concluded. Previous research has shown evidence of less memory decline and brain atrophy in aging females compared to males. Healthy, aging females are also more likely to outperform males on cognitive tests.

“It’s not that men’s brains age faster — they start adulthood about three years older than women, and that persists throughout life,” Goyal said. “What we don’t know is what it means. I think this could mean that the reason women don’t experience as much cognitive decline in later years is because their brains are effectively younger, and we’re currently working on a study to confirm that.”

The brain’s sugar use (or glycolysis) “might explain some of this resilience, since brain aerobic glycolysis is involved in learning and neurite growth,” but researchers note there are likely many factors (like hormones) influencing sex differences on the brain.

Researchers are currently studying a different cohort to validate metabolic brain age, “determine its predictive potential, and answer why sex might affect it.”

Read the full study at pnas.org.