How an Amish Gene May Add a Decade to Life

Jason Ageing, Health, Lifestyle, Science

In a community of Old Order Amish near Berne, Indiana, researchers at Northwestern University uncovered a unique, “private” gene mutation in the SERPINE1 gene, which encodes the blood clotting protein PAI‑1. Individuals with one mutated copy of this gene lived almost 10 years longer than their counterparts—averaging around 85 years instead of the community’s typical 71—or early 70s.

Inspired by this mutation, scientists partnered with Tohoku University (Japan) to develop oral PAI‑1 inhibitors such as TM5614, aiming to mimic the Amish gene’s beneficial effects.

Progress so far:

  • Phase 1 trials in Japan confirmed safety and tolerability among healthy volunteers (~160 individuals).

  • Phase 2 studies are underway, including tests in individuals with type 2 diabetes, obesity, or undergoing chemotherapy, to assess metabolic improvements and stem-cell release.

Meanwhile, in animal studies, the outcomes have been extraordinary:

  • Mice genetically prone to rapid aging and high PAI‑1 levels experienced hair regrowth, improved organ health, and 4× extended lifespan when treated with the drug

The Amish are a genetically closed population, descended from just ~500 18th-century settlers. One couple likely introduced this rare SERPINE1 mutation, which then spread due to their endogamous mating patterns.

This isolation also led to amplification of other genetic disorders—both benign and harmful—but uniquely positions them as valuable subjects for genetic aging studies.

It’s crucial to remember the broader Amish lifestyle advantages seen in other studies:

  • Physical activity is intense; Amish men average ~18,000 steps/day and women ~14,000—far above average.

  • Low obesity rates (~4% vs ~36% in the general U.S.), modest diabetes, and lower cancer incidence, thanks to minimal tobacco use and strong familial support.

So, the gene is only one piece of a complex puzzle that includes environment, culture, and social structure.

So, Could This Work for Everyone?

Researchers are optimistic:

  • The Amish mutation appears safe in carriers with one mutated copy.

  • Targeted drug therapies may replicate the benefits—potentially extending both lifespan and healthspan.

  • However, caution is essential: boosting cell replication long-term might raise cancer risk.

  • Any therapeutic strategy will require rigorous, long-term trials in humans.

Why Do We Die When We Get old?

Jason Ageing, Health, Science

Let’s imagine for a moment that we could completely eliminate cardiovascular diseases — the world’s biggest killer, responsible for more than one in three deaths globally. You might think that eradicating such a major cause of death would dramatically boost human life expectancy. However, the reality is far less impressive: doing so would add only about two extra years to the average lifespan.

What if we also managed to completely cure cancer? That should give us a huge longevity bonus, right? In fact, curing cancer would extend life expectancy by roughly three years. Taken together, completely curing both cardiovascular diseases and cancer — which account for over half of all deaths — would only grant us about five additional years of life on average.

This is a surprising and somewhat sobering realization. Why would removing the top two killers result in such a modest gain?

The answer lies in the nature of aging and the multitude of diseases it brings. As people grow older, they become increasingly vulnerable to a wide range of chronic, degenerative conditions. By the age of 65, about half of individuals are already living with at least two chronic diseases. After 70, about half are considered multimorbid, meaning they suffer from three or more chronic conditions at the same time.

If you remove one major cause of death, another steps up to take its place. The body, already weakened and damaged by the aging process, becomes a target for other age-related diseases such as neurodegenerative disorders, kidney failure, diabetes complications, infections, and frailty-related problems.

Ultimately, what really limits human lifespan isn’t just one or two specific diseases, but the fundamental process of aging itself — a gradual, systemic decline that increases vulnerability across the board. The accumulation of cellular damage, loss of regenerative capacity, and the breakdown of biological systems all conspire to make us susceptible to a host of different fatal outcomes.

In other words, as long as we do not address the root causes of aging, simply knocking out individual diseases will only buy us small, incremental gains. If we truly want to extend healthy human life significantly, we would need to focus on slowing, stopping, or reversing the biological aging process itself — rather than playing whack-a-mole with individual diseases.

The Fountain of Youth, 1546 painting by Lucas Cranach the Elder