Plasminogen activator inhibitor-1 (PAI-1) is mainly known for its aid in regulating blood clots to prevent bleeding disorders. However, scientists also observed that PAI-1 may have other functions that affect aging. For example, when upregulated in mice, PAI-1 was associated with early aging and balding, as well as early death due to heart attacks. In humans, an abundance of PAI-1 is associated with a higher rate of diabetes and early death due to cardiovascular disease. Increased levels of PAI-1 clearly are not good, but what are the effects of a downregulation of PAI-1?
The Amish Population in Berne, Indiana
In 1991, it was discovered that 5% of the small Amish community living in Berne, Indiana had a mutation that lowered levels of PAI-1. To understand how this decrease in PAI-1 affected the health of the population, Dr. Douglas Vaughan, a cardiologist at Northwestern University, reached out and asked if he could study them. They agreed, and one by one, arrived to Vaughan’s temporary testing center, many by horse and buggy. In the end, data from blood tests, heart ultrasounds, and examinations of cardiac and pulmonary function was collected from 177 different people.
Remarkably, the average lifespan of an Amish person from Berne, Indiana with the mutation that downregulated PAI-1 was 85 years of age, which is over 6 years longer than the average American lifespan of 78.7 years and 10 years longer than the average lifespan of an Amish person from Berne without the mutation. In addition, those who had the mutation that downregulated PAI-1 had an astonishing 0% rate of Type II diabetes, while those without the mutation had a 7% rate of Type II diabetes. For those with the mutation, cardiovascular health was also improved, and their DNA had longer telomeres (protective endings on chromosomes), which indicate that a cell is still young, as telomere length decreases as cells divide.
The Amish population that was studied all lived under the same conditions, from climate to food, yet those with the mutation that downregulated PAI-1 were healthier than their counterparts, showing strong evidence that lower levels of PAI-1 can improve the longevity of humans.
These findings show plenty of promise, as scientists are hoping to use these findings in the future to create PAI-1-reducing drugs for those who have a high chance of Type II diabetes or cardiac issues.
Darlene Fung ’19