Internal 'Fountain Of Youth': Genetic Mutation In Indiana Amish Family Found To Protect Against Aging

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Northwestern Medicine researchers have discovered a genetic mutation in an Old Order Amish extended family in Berne, Indiana that is offering a protective benefit against biological aging.

In a study published in the journal Science Advances, the researchers showed that immediate members and relatives of an Amish family with the mutation lived over 10 percent longer and had 10 percent longer telomeres, the protective cap at the end of chromosomes considered to be a biological marker for aging, compared to those who did not.

Additionally, the mutation also resulted in significantly lower levels of fasting insulin and less diabetes, as well as retained blood vessel flexibility arising from lower vascular age based on a composite measure.

"The findings astonished us because of the consistency of the anti-aging benefits across multiple body systems," said Dr. Douglas Vaughan, the study's lead author, adding that not only did those with the mutation live longer but they were also healthier.

"It's a desirable form of longevity."

As a cardiologist, Vaughan has been studying the plasminogen activator inhibitor or PAI-1, a protein part of a molecular fingerprint that is related cell senescence or aging. Amish individuals with the mutation were found to have very low PAI-1 levels.

Longevity Drug Under Development

In partnership with Tohoku University, Northwestern Medicine has developed an oral drug called TM5614 to inhibit PAI-1 action. A phase 1 trial of the drug has been completed in Japan, while phase 2 trials are underway in the U.S.

Northwestern is also set to apply for approval from the Food and Drug Administration to begin an early phase trial in the country, possibly within the next six months. The proposed trial will assess the effects of TM5614 on insulin sensitivity for people diagnosed with obesity and type 2 diabetes.

In the study, carriers of the mutation recorded almost 30 percent lower levels of fasting insulin and had complete protection against diabetes.

Amish Kindred In Berne, Indiana

The Amish kindred (relatives and immediate family) involved in the study are culturally and genetically isolated, with most at least related distantly. Their ancestors emigrated to the area from Berne, Switzerland in the mid-19th century, which is why the town's architecture resembles a lot of Swiss structures.

The mutation was introduced by Swiss farmers who moved to Berne, Indiana. They had two descendants who passed it on to the Amish community after marriage. Outside of Berne, Amish communities don't have the mutation.

As such, Vaughan called it a "private mutation."

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