Stress may cause women's brains to age prematurely

Despite the fact that women live longer than men, their brains seems to age faster. The reason? Possibly a more stressful life.

When people age, some genes become more active while others become less so. In the human brain, these changes can be observed through the "transcriptome" ? a set of RNA molecules that indicate the activity of genes within a population of cells.

When Mehmet Somel, a computational biologist at the University of California, Berkeley, and his colleagues compared the transcriptome of 55 male and female brains of different ages, they were surprised to find that the pattern of gene activation and deactivation that occurs with ageing appeared to progress faster in women than in men. This was particularly apparent in an area of the pre-frontal cortex.

"This was just the opposite of what we'd originally expected," says Somel, who was at the Shanghai Institutes for Biological Sciences in China when he did the research. He says that given the fact that females have a longer lifespan, they had expected to see slower or later ageing-related changes in their brain. "But it fits everyday observations on ageing. Not all organs within an individual age at the same rate," he says.

Somel's team compared the expression of more than 13,000 genes in four brain regions. In one region ? the superior frontal gyrus ? they found 667 genes that were expressed differently in men and women during ageing. Of those, 98 per cent were skewed towards faster ageing in women.

Some of these gene changes have previously been linked to general cognitive decline and degenerative disease.

Stressful life

However, sex differences were not uniform among all women. About half the women showed accelerated age-related changes. The researchers say that this hints towards the cause being environmental rather than simply biological.

Somel says: "A higher stress load could be driving the female brain towards faster ageing-related decline." His team found tentative support for that theory in a study of monkeys, where stress induced similar changes to their brain transcriptome.

Cyndi Shannon Weickert from Neuroscience Research Australia in Sydney, says the initial results are interesting but the connection to stress is speculative. She says it would help to know whether the subjects had other medical conditions at the time of death that might have affected their brain transcriptome. She notes that stress is only one possible cause of these effects. Inflammation, for example, might lead to similar genetic changes.

Next, Somel is planning to test the effects of stress on the brain transcriptome of rodents. He would also like to compare stress and age-related neurodegenerative disease patterns across cultures, where female roles vary. "If the mechanism we hypothesise is correct, any policy that ensures equality in opportunity and empowers women could improve future health."

Journal reference: Aging Cell, DOI: 10.1111/j.1474-9726.2012.00859.x

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