This is the brain on age

Men and women’s brains age differently, a new study demonstrates.

Researchers led by Carl Cotman and Nicole Berchtold at the University of California, Irvine, find that the activity of genes in men’s brains begins to change earlier than it does in women’s brains. The types of genes that change with age also differ between the sexes.

The study, which appears online September 22 in the Proceedings of the National Academy of Sciences, also found that in both genders, each part of the brain examined had its own pattern of aging.

“This is a very interesting study in what is, curiously, an under-studied area, normal aging,” says Etienne Sibille, a neuroscientist at the University of Pittsburgh, who was not involved in the study. “You have a combination of expected and surprises in each finding.” For instance, the fact that men and women’s brains age differently could be predicted based on women’s increased longevity, but the type and scope of the differences were unexpected, he says.

Cotman and Berchtold and their colleagues collected brains from people who had died of various causes between ages 20 and 99. The researchers isolated messenger RNA, or mRNA, from the people’s brains. Messenger RNA is a courier molecule that carries instructions encoded in genes to the cellular machinery that will build proteins using those instructions. Genes that produce higher levels of mRNA are more active.

The researchers examined gene activity in four parts of the brain: the hippocampus, the entorhinal cortex, the postcentral gyrus and the superior frontal gyrus.

Brain scientists expect changes in gene activity as the brain ages, and previous studies have demonstrated some changes in other parts of the brain. Cotman and his colleagues thought the parts of the brain that would have the most change in gene activity would be the hippocampus and entorhinal cortex, because they are most vulnerable to diseases of aging, such as Alzheimer’s.

But the team discovered that these disease-susceptible parts of the brain in older people have the least amount of change in gene activity when compared to younger people. In contrast, the postcentral gyrus, a part of the brain dedicated to perception, changes most. Scientists had expected that region to have the least change, if any.

“This is one of those fun head-scratchers, which is what science is all about,” Cotman says.

Overall gene activity was similar in people aged 20 to 59. And people aged 60 to 99 showed similar patterns of overall gene activity. But the team detected variability in their data. Cotman and Berchtold sat down to discuss the source of the variability and decided to see whether gender differences might explain it. “She thought it was the men, and I said it was the women,” Cotman laughs.

“The big surprise, and one I wasn’t too happy about frankly, was that with age, men show changes in metabolic activity,” Cotman says. Specifically, genes that control energy production in the brain are less active in men starting at about age 60, meaning that metabolic activity slows down. But after the initial drop in activity, men stabilize their gene activity and show no further decline after age 80, the researchers found.

Women’s brains change too, but the changes begin later and keep marching on the older women get, Berchtold says. Women showed gene activity changes in genes that help establish connections between brain cells and in genes that control information exchange in the brain. Women also showed a drop in energy production, but the decrease was not as great as for men.

“What I think it means, especially for men, is that interventions — either lifestyle or medication — may be needed to keep these energy pathways robust,” Berchtold says. Cotman agrees. He pointed out (on his way to a tennis lesson) that exercise is a good way to keep metabolic genes in the brain going strong.