A rare genetic variant found in an Indiana Amish community is sparking groundbreaking research at Northwestern’s Human Longevity Lab, with the potential to change how we age. 

In a quiet, Amish town in northeastern Indiana, a rare genetic gift has been passed down for generations. Here, 10 percent of the community carries a variant that protects against biological aging. Their lineage traces back to a single ancestor from the late 1800s – a man with 17 children and 142 grandchildren – unknowingly passing down his superpower.  

This “old-order” community Dr. Douglas Vaughan, director of Northwestern’s Human Longevity Lab (HLL), refers to serves as both the founder population and the inspiration behind its research. Established in 2022, the HLL is a research center dedicated to studying biological aging.

The limited genetic variant found in this Amish community is also referred to as plasminogen activator inhibitor-1 (PAI-1), a protein that regulates blood clotting. People with a PAI-1 deficiency have lower fasting insulin levels, are protected from diabetes and heart disease, and have a younger cardiovascular system, ultimately living longer than their unaffected kindred. But PAI-1 deficiency is incredibly rare, found in only about one in 100,000 people. 

“I think it’s the only genetic variant in the world that actually protects against biological aging in our species in a real way,” HLL Director Vaughan says. “And I actually think it represents Mother Nature tinkering with our genome a little bit.” 

The Montreal Cognitive Assessment (MoCA). Photo courtesy of Shane Collins.

The subject of aging can be a turnoff unless it is thought of as an opportunity, as for Dr. Vaughan, this is his life’s work. Vaughan explains that aging is the greatest risk factor for major diseases like heart disease, cancer, dementia, diabetes and lung disease. Since aging itself increases susceptibility to illness, his team’s work focuses on slowing the aging process.  

Vaughan and his collaborators at the HLL are trying to answer the question: how can we bring this unique genetic advantage of this rare Amish community in northeastern Indiana to the rest of human beings? 

The HLL enrolls diverse participants to study ways to slow biological aging, prioritizing those most at risk – including people with chronic HIV, inflammatory conditions or exposure to chemotherapy and toxins. Unlike many longevity programs focused on studying healthy individuals to make them healthier, the HLL is looking to find pragmatic interventions that are scalable, affordable and equitable to help those most vulnerable to aging. By doing so, they hope to extend health spans – the years lived in good health, free from serious illness – and delay the onset of age-related diseases. 

Taking Vital Signs-BP/Heart Rate at the HLL. Photo courtesy of Shane Collins.

Doctors around the world are searching for ways to extend health span; not just adding years to life, but ensuring those years are filled with health and wellness. The challenge has always been measurement: how do they track the pace of aging, and which interventions make a real difference? 

Dr. Manjot Gill, vice chair of clinical performance and ophthalmology at the HLL, highlights that this is a defining moment in history, where doctors can not only measure biological age but also explore ways to influence it. With a multidisciplinary approach, the team studies aging across various organ systems, taking a scientific and comprehensive view. They hope to integrate clinical trials and treatment interventions within the HLL to assess whether these strategies are truly effective in slowing the biological age. 

“I think for the first time, because we are really looking at it very scientifically, there will be interventions that one will have available in our lifetime that can help in terms of delaying or slowing this,” Gill says. 

At the HLL, experts measure biological age using factors like blood pressure, gait speed, grip strength, lung capacity and heart activity. They also analyze DNA methylation (chemical modifications that regulate gene activity), epigenetic patterns (which influence how genes are expressed without altering DNA sequences) and retina images. Using AI-based tools and global research teams, they identify the markers of healthy aging to determine a person’s biological age in 2025, categorizing them as an accelerated, normal or super-ager. Vaughan’s optimism lies in the likelihood of finding those elements that might positively bend the curve of aging in people that are on an accelerated aging path. 

The testing process at the HLL. Photo courtesy of Vaughan.

“More than anything else, I want to see if we can do something for people that are disadvantaged and, you know, bring this science out into the mainstream,” Vaughan says. 

Dr. Josh Cheema, director of AI-Based analytics at the HLL, explains that while many longevity clinics in Chicago offer therapies and can prescribe any drug they think will be helpful, there’s no solid evidence proving their effectiveness in humans, as all longevity research thus far has solely been tested on animals. He expresses excitement for real data on humans to emerge at the HLL, considering that many proposed treatments – from dental therapies to hormone injections and red-light therapy – might work, but doctors simply don’t know how effective they are. 

“I think the thing that I’m most excited about is people coming to a consensus on what the most important metrics are,” Cheema says. “To measure, to actually get a sense of how fast or how slow someone is aging, and then to have real clinical data in human beings about the different interventions that people talk about.” 

Body Composition Testing in BodPod at the HLL. Photo courtesy of Shane Collins.

For 15 years, Vaughan has collaborated with a research team in Japan that developed a pill-form small-molecule inhibitor of PAI-1, now in phase III trials for various cancers. While its effects on aging remain unstudied, he hopes to soon test whether reducing PAI-1 can slow aging beyond the Indiana founder population. 

The vision extends beyond having a single lab in Chicago, with the hope of building a global network of laboratories, all equipped to conduct the same specialized measurements and research as the HLL. In a few months, a partner laboratory will be opening at Tohoku University in northern Japan, with plans underway to also establish a facility in South Africa as well. 

The pursuit has never felt more urgent, or more promising.  

“We’re in this unique moment in human history right now that makes me optimistic that we can find some things that might work, and it’s because the biology of aging is being demystified, and our ability to measure biological age in a person is getting much more precise,” Vaughan says. “With those two things coming together, it makes me think that we can probably find something that could work and have some benefit in people independent of their background or their culture, or their diet or their climate.” 

 Header Photo courtesy of Shane Collins