How a genetic mutation is helping an Amish community live longer and healthier

A genetic mutation found in an Amish community might reveal the key to living longer and healthier.  The study, published in Science Advances, found that a mutation on the SERPINE gene halves the normal level of Plasminogen Activator Inhibitor-1 (PAI-1), a protein that is necessary for blood clots.  In the 1990’s it was discovered that some Amish family members from Indiana carried a double mutation of PAI-1, which results in a rare bleeding disorder.  Interestingly, other Amish members that only had a single mutation of PA1-1 did not have the rare bleeding disorder, but lived significantly longer than those without any PAI-1 deficiency.  So how could a rare genetic mutation actually extend our lifespan?

Scientists studied 177 members of the Old Order Amish from Berne, Indiana and found that 43 of the members had a single mutation of PAI-1.  This mutation cut their PAI-1 levels to half the normal amount.  The goal of the study was to determine if this single mutation resulted in improved anti-aging outcomes.  Their results were striking; carriers of the single mutation lived, on average, 10 years longer than members without the mutation. They also appeared to be protected from type 2 diabetes, with a 0% incidence rate versus 7% in those with no mutation.  In addition, those with a single mutation had lower fasting insulin rates, a hormone that when elevated, can lead to diabetes.  They also displayed increases in telomere length, a validated biological marker of aging.  A telomere “caps” the end of a chromosome, and protects our genetic material from degrading.  Longer telomeres have been strongly linked to longevity.  

The results of the study were impressive, as they found consistent anti-aging effects from a single PAI-1 mutation across multiple body systems.  This study confirmed that PAI-1 is strongly associated with the aging process, which is crucial because PAI-1 has been a target of several anti-aging therapeutics.  Inhibition of PAI-1 in mouse models of aging extends their lifespan, and protects their lungs and vascular system from accelerated aging.  Currently, a PAI-1 inhibitor is undergoing early-phase clinical studies in Japan.  There are still several questions that scientists need to address before PAI-1 inhibition is touted as the next anti-aging fix.  First, Amish members overall live longer than the average American, even without the mutation.  This suggests that there are factors besides a PAI-1 mutation that influence the aging process.  In addition, inhibiting PAI-1 too much would be dangerous.  As previously mentioned, those with a double mutation of PAI-1 are diagnosed with a rare bleeding disorder, so it will be critical to be able to control the level of inhibition.  By identifying the genetic influences of PAI-1 on aging, scientists are one step closer to developing targeted anti-aging therapeutics that go beyond your drugstore wrinkle cream.

Paper: A null mutation in SERPINE1 protects against biological aging in humans

Published: Science Advances, November 15th, 2017

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