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Doctor Doug Vaughan’s mouse was not well. It was completely bald, close to a heart attack and its brain was filled with protein plaques that, if they were found in a human brain, would indicate Alzheimer's disease. It showed all the signs of extreme ageing, even though other mice of a similar age in the lab at the Feinberg School of Medicine in Chicago were perfectly youthful.

For Vaughan, these dire vital signs meant that his experiment was going perfectly. The mouse had been genetically modified so its body made far too much of a protein called PAI-1 that accelerates ageing. Although it was a young mouse on paper, biologically-speaking it was already living on borrowed time.


That all changed when Vaughan received a parcel from Toshio Miyata, a professor at Tohoku University in Sendai, Japan. The parcel contained an experimental drug that Miyata hoped would reduce the amount of PAI-1 in the mouse’s body and reverse its extreme ageing. Intrigued by the drug’s potential, Vaughan sneaked it into the mouse’s food, hoping it would stay alive long enough to demonstrate whether the drug had any effect. Mice with this particular genotype have an unfortunate habit of suddenly dropping dead with little warning.

After the mouse had been taking the drug for a couple of weeks, Vaughan noticed that it had started growing hair again and its health was improving. It was getting younger in front of his eyes. Miyata’s drug, it seemed, could slow down the cellular process that drag bodies towards old age and, ultimately, death.

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New research now shows that some humans possess a genetic equivalent to Miyata’s drug. A small number of Amish people in the US state of Indiana have a genetic mutation that cuts their PAI-1 levels in half, and adds on average ten years to their lifespan. Even older people with the mutation have remarkably elastic blood vessels, an indicator of good vascular health.

“I think something like this could be part of the anti-ageing solution to extend the lifespan of individuals,” Vaughan says. If we can replicate this genetic mutation in other people, we could have found a way to fight the most inevitable of all illnesses – old age.


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The Amish community in Indiana has often been the subject of ageing studies. In the last century, the average lifespan of an American has increased from around 50 to the mid-70s. Over the same period, the average Amish lifespan has consistently been in the low 70s.

Yet Amish people don’t participate in many aspects of twenty-first century life. “These Amish live an eighteenth century lifestyle, they don’t avail themselves of modern medicine to any intensive degree,” Vaughan says. They don’t vaccinate as much as other Americans and tend not to have health checks, such as colonoscopies, that are crucial for early diagnosis of potentially fatal cancers. If they did participate in modern medicine, Vaughan thinks that some Amish people could have a much better of chance of reaching unusually long lifespans.

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The number of people with this long-life mutation is vanishingly small. “I think this mutation may only be present in this Amish kindred in northern Indiana,” Vaughan explains. “It doesn’t exist in the population at large.” He says the mutation can be traced back to a single ancestral couple, who emigrated from Switzerland in the middle of the eighteenth century. It was initially discovered because a young girl in the community had a condition that leads to excessive blood clotting. Researchers eventually worked out that she had two copies of the mutation that is linked to longevity.


Vaughan and his team of 40 researchers drove to northern Indian and set up a makeshift medical centre where they could take blood samples from members of the Berne Amish Community. About half of the people contacted went to have their blood drawn, traveling by horse and buggy to help out with the research. “They were curious about the mutation and the idea that it might be linked to ageing and health,” Vaughan says. Standing in the medical centre, he couldn’t help but look out for people that looked both old and young at the same time. “I wanted to look at their hair but they keep their hats on,” he says, jokingly.

In the end Vaughan identified 43 people with the mutation who, on average, lived ten years longer than other people in the community. By his estimates there may be up to 300 more people with the same mutation, around five per cent of the Berne Amish kindred. Before he started the experiment, Vaughan had no idea he was going to uncover such a clear link between the mutation and longevity. “I was very surprised,” he says.

The key to the longevity of the Berne Amish is hidden deep within every single cell in their body. For several decades, scientists have known that biological ageing is linked to the length to of telomeres – small caps on the ends of strands of DNA that protect our chromosomes and are crucial for cell replication. This is the process that keeps our bodies going as we get older. “As we age all of us lose some of the ends of our chromosomes,” Vaughan says. “It tracks our gradual descent into oblivion.”

As we get older, those telomeres get shorter and cells eventually lose the ability to replicate. These non-replicating cells and tissues release large amounts of PAI-1 – the same protein that was behind the extreme ageing of Vaughan’s mouse.

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The 43 people Vaughan identified all had a mutation in one copy of the SERPINE1 gene, which encodes the expression of PAI-1. One of their SERPINE1 genes didn’t work at all, which means they have half the normal amount of PAI-1, reducing the rate at which their telomeres shorten and thus increasing their lifespan.

Vaughan’s results imply that if we could find a way of inactivating one copy of our SERPINE1 gene, we might be able to trigger the same kind of lifespan increase seen in his mouse, and the 43 Amish people. The people he studied seemed perfectly healthy with half the normal amount of PAI-1, so at this early stage there is no real indication that inducing this mutation would be dangerous.

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But how can we benefit from this potentially life-extending discovery? One option could be editing the genome of human embryos using CRISPR. Earlier this year, researchers from China and America did exactly that, although so far none of this research has been carried out in embryos that are destined to become a human baby. “That’s going to take years or decades to become mainstream,” says Vaughan.


Instead, Vaughan thinks that we could create drugs that inhibit the creation of PAI-1 in our bodies, like the drug he gave to his aged mouse. In Japan, Miyata is already trialling the drug in humans, and Vaughan says that a good way to test its impact would be to give it to groups of people that age very quickly, such as people with chronic HIV infections. In the meantime, Miyata is thinking of licensing the drug as a local treatment for baldness.

A reduction of PAI-1 appears to be linked to a wide range of health benefits, including improved metabolism and lower incidences of diabetes. Obese mice given the PAI-1-reducing drug also find it easier to lose weight. But there is a darker side to human longevity too. The longer we keep our cells replicating for, the higher the chance of us developing cancer becomes, as during cell replication cancer-causing mutations can creep into our DNA.

For the time being, Vaughan says, the future of humanity longevity lies somewhere along the thin line between cell death and cancer.