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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