Rare Genetic Mutation in Indiana Amish Protects Against Diabetes and Appears to Extend Life

The clinic parking lot in Berne, Ind., where some of the Amish residents carry a genetic mutation that may have life-extending benefits.
Courtesy of Indiana Hemophilia & Thrombosis Center

Amish people living in a rural part of Indiana have a rare genetic mutation that protects them from Type 2 diabetes and appears to significantly extend their life spans, according to a new study.

The findings, published on Wednesday in the journal Science Advances, shed light on the processes underlying cellular aging and could lead to new therapies for chronic diseases, some experts say. The researchers are planning at least one follow-up trial that will recreate the effects of the mutation so they can study its impact on obese people with insulin resistance, a precursor to diabetes.

The mutation described in the new paper affects a mysterious protein called plasminogen activator inhibitor-1, or PAI-1, that is known primarily for its role in promoting blood clotting. The mutation was first identified in 1991 in a secluded Amish farming community in Berne, Ind. An estimated 5 percent of the community carries the mutation, which causes them to produce unusually low levels of PAI-1.

Scientists have long suspected that PAI-1 has other functions outside of clotting that relate to aging. Dr. Douglas Vaughan, a cardiologist at Northwestern medical school, noticed, for example, that mice that had been genetically engineered to produce high levels of the protein age fairly quickly, going bald and dying of heart attacks at young ages. People who have higher levels of the protein in their bloodstreams also tend to have higher rates of diabetes and other metabolic problems and to die earlier of cardiovascular disease.

Dr. Vaughan wondered how the Amish people in Berne who naturally produce smaller amounts of PAI-1 are affected. So two years ago he reached out to the community and asked if he could study them.

When they agreed, Dr. Vaughan took a team of 40 researchers to their town, set up testing stations in a recreation center, and spent two days doing extensive tests on 177 members of the community, many of whom arrived by horse and buggy. The researchers pored over birth and death records and took extensive genealogical histories. They drew blood, did ultrasounds of their hearts, and rigorously examined their cardiac and pulmonary function.

“Some of the young men we collected blood from fainted because they had never had a needle stick in their life,” said Dr. Vaughan, who is chairman of medicine at the Northwestern University Feinberg School of Medicine. “These people live sort of an 18th century lifestyle and generally don’t take advantage of modern medicine. But they were so gracious and courteous and cooperative.”

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SOURCE: New York Times, Anahad O’Connor