A rare mutation found in an Amish population in Indiana may shed new light on how to fight back against aging, researchers have found. The gene, called SERPINE1, may be found in up to 5 percent of the Amish people in this particular community, founded by a couple from Switzerland. And the protein it codes for may provide a new target for anti-aging drugs.
"This is one of the first clear-cut genetic mutations in human beings that acts upon aging and aging-related disease," Dr. Douglas Vaughan told Newsweek. Vaughan is a cardiologist at Northwestern University Feinberg School of Medicine and one of the lead authors of the study, which was published in Science Advances on Wednesday. SERPINE1 makes a protein called plasminogen activator inhibitor-1, or PAI-1, which may play a role in diabetes and Alzheimer's, he noted.
In a typical American, the levels of PAI-1 can be predicted using a person's body mass index. Fat, among other things, produces PAI-1. "The more visceral fat a person has, the higher the PAI-1 level will be," Vaughan said—unless that person has this rare mutation, which can send the protein levels down to almost nothing.
"There are also a number of factors that drive PAI-1 production in the body, including glucose and insulin and inflammation and oxidative stress. All of those factors, in a roundabout way, contribute to aging, and they all sort of converge on PAI-1," he said.
And interestingly, the Amish that carried this mutation also seemed to have longer telomeres than those who did not—about 10 percent longer. Telomeres are sections of DNA that cap chromosomes, and scientists think they may protect the rest of the chromosome from damage. Telomere length has also been linked to cellular aging.
Vaughan and a team of about 40 people went to Indiana to do the testing, which included checking nearly 200 Amish people's heart and lung function as well as doing genetic testing. Stations for all of the tests—and for snacks—were set up in the gym of a recreation center in the farmlands around Berne. "Then the Amish came there in their horse and buggies," Vaughan recalled.
Getting everything set up and done over two days was a major logistical challenge, but actually getting the Amish to work with researchers was not.
Vaughan had a long-term relationship with a local specialist, which helped. And the Amish themselves were curious, he said. "In general, they don't avail themselves of modern medicine to a great degree. But they were very cooperative and willing to undergo some pretty intensive testing."
"It was the experience of a lifetime," Vaughan said. "It's been a very gratifying and wonderful opportunity to be a part of this work."
However, the study was fairly small—only 177 people were tested, and only 43 had the particular mutation that was being studied.
"We'd like to expand the study," he said. Specifically, looking at the way the Amish age or the way their hearing or cognition might change as they age would also be helpful, as would testing more people. "There's a lot more work to do in that regard."
Some other research that might get a boost from more work in this area: anti-aging drugs. "We can develop a drug that actually inhibits the protein and provides a similar benefit as the genetic deficiency does in the Amish."
One of the other authors of the paper, Dr. Toshio Miyata of the Tohoku University Graduate School of Medicine in Japan, has begun early human trials of such an inhibitor. Vaughan, who said he does not have any financial interest in the company developing the drug, said that he has also begun the paperwork to bring a clinical trial of the drug to the U.S. That trial could begin as early as next year.
