A genetic variant that makes small tweaks in an important brain protein may cause aging to hit some people’s brains harder than others.
Pilots’ performance on a flight simulator test generally declines slightly with age. But a new study shows that pilots with a particular version of a gene called BDNF have a faster drop than others. Researchers also observed a decline in the size of an important learning and memory center in the brains of those with the variant, Ahmad Salehi of the Department of Veterans Affairs Palo Alto Health Care System and Stanford University, and colleagues report online October 25 in Translational Psychiatry.
About 38 percent of pilots in the new study carried the variant in either one or both of their copies of the BDNF gene. Over the course of two years the flight simulator scores of all the pilots in the study declined a little with age. But scores of pilots carrying the variant dropped about three times faster than scores of pilots who have the normal version of the gene.
The drop in scores was not so dramatic that pilots should be removed from the cockpit, says Salehi. “It certainly did not disable them at all,” he says. But the score drop did reflect a slightly faster decline in factors like reaction time, navigation skills, plane positioning and performance in emergency situations.
For some of the pilots, the researchers measured the size of the hippocampus, a structure in the brain that is important for learning and memory. After age 65, men who had the alternate version of the gene also lost more hippocampus volume than men with the normal version of the gene, the researchers found. The size of the hippocampus did not correlate with scores on flight simulator tests, probably because flying a plane requires much more of the brain than just the hippocampus, Salehi says.
It’s not just pilots that need to worry about aging brains. “Anybody who works with complex machinery could be in the same situation,” Salehi says.
The genetic variant is a single-unit DNA change in the BDNF gene. That slight modification leads to a swap of the amino acid methionine for a valine at one spot in the protein that the gene encodes. Such a small change can have big consequences for a protein that has changed very little since it first appeared about 400 million years ago, says Salehi. For example, the BDNF protein is usually released from brain cells only when it is needed, but the substitution causes the protein to be pumped out of cells continuously. And in those with the variant, not as much of the protein is made in places where nerve cells receive messages.
Exactly how much of aging’s impact on the brain is caused by genetic differences in BDNF is not clear, says William Mobley, a neurologist and neuroscientist at the University of California, San Diego who was not involved in the study. “It could be one of a thousand factors that plays a role,” he says. But the new work highlights the importance of BDNF and suggests more research is needed to figure out how to counteract the negative effects of the version associated with accelerated cognitive decline.
